| 1. |
- Guillery, Ray, et al.
(författare)
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Editorial note
- 1990
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 2:7, s. 565-565
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Andersson, M, et al.
(författare)
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Time course of striatal DeltaFosB-like immunoreactivity and prodynorphin mRNA levels after discontinuation of chronic dopaminomimetic treatment.
- 2003
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 17:3, s. 661-666
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Tidskriftsartikel (refereegranskat)abstract
- DFosB-like proteins are particularly stable transcription factors that accumulate in the brain in response to chronic perturbations. In this study we have compared the time-course of striatal FosB/DFosB-like immunoreactivity and prodynorphin mRNA expression after discontinuation of chronic cocaine treatment to intact rats and chronic L-DOPA treatment to unilaterally 6-hydroxydopamine (6-OHDA) lesioned rats. The animals were killed between 3 h and 16 days after the last drug injection. In both treatment paradigms, the druginduced FosB/DFosB immunoreactivity remained significantly elevated in the caudate putamen even at the longest withdrawal period examined. The concomitant upregulation of prodynorphin mRNA, a target of DFosB, paralleled the time-course of DFosB-like immunoreactivity in the 6-OHDA-lesion/L-DOPA model, but was more transient in animals treated with cocaine. These results suggest that DFosB-like proteins have exceptional in vivo stability. In the dopamine-denervated striatum, these proteins may exert sustained effects on the expression of their target genes long after discontinuation of L-DOPA pharmacotherapy.
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| 3. |
- Apps, R, et al.
(författare)
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Precise matching of olivo-cortical divergence and cortico-nuclear convergence between somatotopically corresponding areas in the medial C1 and medial C3 zones of the paravermal cerebellum
- 2000
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 12:1, s. 205-214
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Tidskriftsartikel (refereegranskat)abstract
- The paravermal cerebellar cortex contains three spatially separate zones (the C1, C3 and Y zones) which form a functionally coupled system involved in the control of voluntary limb movements. A series of 'modules' has been postulated, each defined by a set of olivary neurons with similar receptive fields, the cortical microzones innervated by these neurons and the group of deep cerebellar nuclear neurons upon which the microzones converge. A key feature of this modular organization is a correspondence between cortical input and output, irrespective of the zonal identity of the microzone. This was tested directly using a combined electrophysiological and bi-directional tracer technique in barbiturate-anaesthetized cats. During an initial operation, small injections of a mix of retrograde and anterograde tracer material (red beads combined with Fluoro-Ruby or green beads combined with biotinylated dextran amine or Fluoro-Emerald) were made into areas of the medial C1 and medial C3 zones in cerebellar lobule V characterized by olivo-cerebellar input from the ventral forelimb. The inferior olive and the deep cerebellar nuclei were then scrutinized for retrogradely labelled cells and anterogradely labelled axon terminals, respectively. For individual experiments, the degree of C1-C3 zone terminal field overlap in the nucleus interpositus anterior was plotted as a function of either the regional overlap of single-labelled cells or the proportion of double-labelled cells in the dorsal accessory olive. The results were highly positively correlated, indicating that cortico-nuclear convergence between parts of the two zones is in close proportion to the corresponding olivo-cerebellar divergence, entirely consistent with the modular hypothesis.
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| 4. |
- Arvidsson, Andreas, et al.
(författare)
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N-methyl-D-aspartate receptor-mediated increase of neurogenesis in adult rat dentate gyrus following stroke
- 2001
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 14:1, s. 10-18
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Tidskriftsartikel (refereegranskat)abstract
- Neurogenesis in the adult rat dentate gyrus was studied following focal ischemic insults produced by middle cerebral artery occlusion (MCAO). Animals were subjected to either 30 min of MCAO, which causes damage confined to the striatum, or 2 h of MCAO, which leads to both striatal and cortical infarction. When compared to sham-operated rats, MCAO-rats showed a marked increase of the number of cells double-labelled for 5-bromo-2'-deoxyuridine-5'-monophosphate (BrdU; injected during 4-6 days postischemia) and neuronal-specific antigen (NeuN; a marker of postmitotic neurons) in the ipsilateral dentate granule cell layer and subgranular zone at 5 weeks following the 2 h insult. Only a modest and variable increase of BrdU-labelled cells was found after 30 min of MCAO. The enhanced neurogenesis was not dependent on cell death in the hippocampus, and its magnitude was not correlated to the degree of cortical damage. Systemic administration of the N-methyl-D-aspartate (NMDA) receptor blocker dizocilpine maleate (MK-801) completely suppressed the elevated neurogenesis following 2 h of MCAO. Our findings indicate that stroke leads to increased neurogenesis in the adult rat dentate gyrus through glutamatergic mechanisms acting on NMDA receptors. This modulatory effect may be mediated through changes in the levels of several growth factors, which occur after stroke, and could influence various regulatory steps of neurogenesis.
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| 5. |
- Barraud, Perrine, et al.
(författare)
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Isolation and characterization of neural precursor cells from the Sox1-GFP reporter mouse.
- 2005
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 22:7, s. 1555-1569
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Tidskriftsartikel (refereegranskat)abstract
- We have made use of a reporter mouse line in which enhanced green fluorescence protein (GFP) is inserted into the Sox1 locus. We show that the GFP reporter is coexpressed with the Sox1 protein as well as with other known markers for neural stem and progenitor cells, and can be used to identify and isolate these cells by fluorescence-activated cell sorting (FACS) from the developing or adult brain and from neurosphere cultures. All neurosphere-forming cells with the capacity for multipotency and self-renewal reside in the Sox1–GFP-expressing population. Thus, the Sox1–GFP reporter system is highly useful for identification, isolation and characterization of neural stem and progenitor cells, as well as for the validation of alternative means for isolating neural stem and progenitor cells. Further, transplantation experiments show that Sox1–GFP cells isolated from the foetal brain give rise to neurons and glia in vivo, and that many of the neurons display phenotypic characteristics appropriate for the developing brain region from which the Sox1–GFP precursors were derived. On the other hand, Sox1–GFP cells isolated from the adult subventricular zone or expanded neurosphere cultures gave rise almost exclusively to glial cells following transplantation. Thus, not all Sox1–GFP cells possess the same capacity for neuronal differentiation in vivo.
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| 6. |
- Bengtsson, Fredrik, et al.
(författare)
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Feedback control of Purkinje cell activity by the cerebello-olivary pathway.
- 2004
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 20:11, s. 2999-3005
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Tidskriftsartikel (refereegranskat)abstract
- The pathway from the deep cerebellar nuclei to the inferior olive, the source of the climbing fibre input to the cerebellum, inhibits olivary transmission. As climbing fibre activity can depress the background firing of the Purkinje cells, it was suggested that nucleo-olivary (N–O) inhibition is a negative feedback mechanism for regulating Purkinje cell excitability. This suggestion was investigated, in a set-up with decerebrate ferrets, both by blocking and by stimulating cerebellar output while recording Purkinje cell activity. Blocking the N–O pathway was followed by an increased climbing fibre activity and a dramatic reduction in simple spike firing. Stimulation of the N–O fibres depressed climbing fibre responses and caused an increase in simple spike firing. These results are taken as support for the feedback hypothesis.
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| 7. |
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| 8. |
- Björkman, Anders, et al.
(författare)
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Phantom digit somatotopy: a functional magnetic resonance imaging study in forearm amputees.
- 2012
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 36:1, s. 2098-2106
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Tidskriftsartikel (refereegranskat)abstract
- Forearm amputees often experience non-painful sensations in their phantom when the amputation stump is touched. Cutaneous stimulation of specific stump areas may be perceived as stimulation of specific phantom fingers (stump hand map). The neuronal basis of referred phantom limb sensations is unknown. We used functional magnetic resonance imaging to demonstrate a somatotopic map of the phantom fingers in the hand region of the primary somatosensory cortex after tactile stump stimulation. The location and extent of phantom finger activation in the primary somatosensory cortex corresponded well to the location of normal fingers in a reference population. Stimulation of the stump hand map resulted in an increased bilateral activation of the primary somatosensory cortex compared with stimulation of forearm regions outside the stump hand map. Increased activation was also seen in contralateral posterior parietal cortex and premotor cortex. Ipsilateral primary somatosensory cortex activation might represent a compensatory mechanism and activation of the non-primary fronto-parietal areas might correspond to awareness of the phantom limb, which is enhanced when experiencing the referred sensations. It is concluded that phantom sensation elicited by stimulation of stump hand map areas is associated with activation of finger-specific somatotopical representations in the primary somatosensory cortex. This suggests that the primary somatosensory cortex could be a neural substrate of non-painful phantom sensations. The stump hand map phenomenon might be useful in the development of prosthetic hand devices.
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| 9. |
- Björkman, Anders, et al.
(författare)
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Rapid cortical reorganisation and improved sensitivity of the hand following cutaneous anaesthesia of the forearm.
- 2009
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 29:4, s. 837-844
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Tidskriftsartikel (refereegranskat)abstract
- The cortical representation of various body parts constantly changes based on the pattern of afferent nerve impulses. As peripheral nerve injury results in a cortical and subcortical reorganisation this has been suggested as one explanation for the poor clinical outcome seen after peripheral nerve repair in humans. Cutaneous anaesthesia of the forearm in healthy subjects and in patients with nerve injuries results in rapid improvement of hand sensitivity. The mechanism behind the improvement is probably based on a rapid cortical and subcortical reorganisation. The aim of this work was to study cortical changes following temporary cutaneous forearm anaesthesia. Ten healthy volunteers participated in the study. Twenty grams of a local anaesthetic cream (EMLA) was applied to the volar aspect of the right forearm. Functional magnetic resonance imaging was performed during sensory stimulation of all fingers of the right hand before and during cutaneous forearm anaesthesia. Sensitivity was also clinically assessed before and during forearm anaesthesia. A group analysis of functional magnetic resonance image data showed that, during anaesthesia, the hand area in the contralateral primary somatosensory cortex expanded cranially over the anaesthetised forearm area. Clinically right hand sensitivity in the volunteers improved during forearm anaesthesia. No significant changes were seen in the left hand. The clinically improved hand sensitivity following forearm anaesthesia is probably based on a rapid expansion of the hand area in the primary somatosensory cortex which presumably results in more nerve cells being made available for the hand in the primary somatosensory cortex.
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| 10. |
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| 11. |
- Carral, V, et al.
(författare)
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A kind of auditory 'primitive intelligence' already present at birth
- 2005
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 21:11, s. 3201-3204
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Tidskriftsartikel (refereegranskat)abstract
- 'Primitive intelligence' in audition refers to the capacity of the auditory system to adaptatively model the acoustic regularity and react neurophysiologically to violations of such regularity, thus supporting the ability to predict future auditory events. In the present study, event-related brain potentials to pairs of tones were recorded in 11 human newborns to determine the infants' ability to extract an abstract acoustic rule, the direction of a frequency change. Most of the pairs (standard, P = 0.875) were of ascending frequency (i.e. the second tone higher than the first), while the remaining pairs (deviant, P = 0.125) were of descending frequency (the second tone being lower). Their frequencies varied among seven levels to prevent discrimination between standard and deviant pairs on the basis of absolute frequencies. We found that event-related brain potentials to deviant pairs differed in amplitude from those to standard pairs at 50-450 ms from the onset of the second tone of a pair, indicating the infants' ability to represent the abstract rule. This finding suggests the early ontogenetic origin of 'primitive intelligence' in audition that eventually may form a prerequisite for later language acquisition.
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| 12. |
- Cenci Nilsson, Angela, et al.
(författare)
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Striatal c-fos Induction by Cocaine or Apomorphine Occurs Preferentially in Output Neurons Projecting to the Substantia Nigra in the Rat
- 1992
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 4:4, s. 376-380
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Tidskriftsartikel (refereegranskat)abstract
- Fluorogold or rhodamine-labelled latex beads were injected in the substantia nigra (SN) or the globus pallidus (GP) in order retrogradely to label striatal output neurons that project to the two target structures. Ten days later, striatal c-fos was induced by systemic administration of cocaine (five normal rats; 25 mg/kg cocaine i.p. 2 h before killing) or apomorphine (five unilaterally dopamine-denervated rats; 0.25 mg/kg apomorphine s. c. 2 h before killing), and detection of the Fos protein in the striatum was achieved by immunofluorescence. Sections through the caudate-putamen that displayed good labelling from both SN and GP were selected for a quantitative analysis: the number of retrogradely labelled cells that exhibited Fos immunoreactivity, as well as the total number of retrogradely labelled cells located within a grid (0.16 mm2 in size) were counted manually at 25 x magnification. Cocaine induced a proportionally higher c-fos expression in striato-nigral compared to striato-pallidal neurons, whereas apomorphine activated Fos almost exclusively in striato-nigral neurons. The present findings are consistent with the idea that striatal c-fos induction by dopaminergic agents is primarily mediated by an interaction with D1-receptors, which are thought to be selectively localized on neurons projecting to SN.
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| 13. |
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| 14. |
- Danilov, Alexandre, et al.
(författare)
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Neurogenesis in the adult spinal cord in an experimental model of multiple sclerosis
- 2006
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 23:2, s. 394-400
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis is an inflammatory disease of the central nervous system characterized by inflammation, demyelination, axonal degeneration and accumulation of neurological disability. Previously, we demonstrated that stem cells constitute a possible endogenous source for remyelination. We now addressed the question of whether neurogenesis can occur in neuroinflammatory lesions. We demonstrated that, in experimental autoimmune encephalomyelitis, induced in rats 1,1'-dioctadecyl-6,6'-di(4sulphopentyl)-3,3,3',3'tetramethylindocarbocyani n(DiI)-labelled ependymal cells not only proliferated but descendants migrated to the area of neuroinflammation and differentiated into cells expressing the neuronal markers beta-III-tubulin and NeuN. Furthermore, these cells were immunoreactive for bromodeoxyuridine and PCNA, markers for cells undergoing cell proliferation. Using the whole-cell patch-clamp technique on freshly isolated 1, DiI-labelled cells from spinal cord lesions we demonstrated the ability of these cells to fire overshooting action potentials similar to those of immature neurones. We thus provide the first evidence for the initiation of neurogenesis in neuroinflammatory lesions in the adult spinal cord.
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| 15. |
- Darsalia, Vladimer, et al.
(författare)
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Survival, migration and neuronal differentiation of human fetal striatal and cortical neural stem cells grafted in stroke-damaged rat striatum
- 2007
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 26:3, s. 605-614
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Tidskriftsartikel (refereegranskat)abstract
- Stroke is a neurodegenerative disorder and the leading cause of disability in adult humans. Treatments to support efficient recovery in stroke patients are lacking. Several studies have demonstrated the ability of grafted neural stem cells (NSCs) to partly improve impaired neurological functions in stroke-subjected animals. Recently, we reported that NSCs from human fetal striatum and cortex exhibit region-specific differentiation in vitro, but survive, migrate and form neurons to a similar extent after intrastriatal transplantation in newborn rats. Here, we have transplanted the same cells into the stroke-damaged striatum of adult rats. The two types of NSCs exhibited a similar robust survival (30%) at 1 month after transplantation, and migrated throughout the damaged striatum. Striatal NSCs migrated farther and occupied a larger volume of striatum. In the transplantation core, cells were undifferentiated and expressed nestin and, to a lesser extent, also GFAP, beta III-tubulin, DCX and calretinin, markers of immature neural lineage. Immunocytochemistry using markers of proliferation (p-H3 and Ki67) revealed a very low content of proliferating cells (< 1%) in the grafts. Human cells outside the transplantation core differentiated, exhibited mature neuronal morphology and expressed mature neuronal markers such as HuD, calbindin and parvalbumin. Interestingly, striatal NSCs generated a greater number of parvalbumin(+) and calbindin(+) neurons. Virtually none of the grafted cells differentiated into astrocytes or oligodendrocytes. Based on these data, human fetal striatum- and cortex-derived NSCs could be considered potentially safe and viable for transplantation, with strong neurogenic potential, for further exploration in animal models of stroke.
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| 16. |
- Ekdahl, Christine T, et al.
(författare)
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Caspase inhibitors increase short-term survival of progenitor-cell progeny in the adult rat dentate gyrus following status epilepticus
- 2001
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 14:6, s. 937-945
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Tidskriftsartikel (refereegranskat)abstract
- The dentate gyrus (DG) is one of the few regions in the brain that continues to produce new neurons throughout adulthood. Seizures not only increase neurogenesis, but also lead to death of DG neurons. We investigated the relationship between cell death and neurogenesis following seizures in the DG of adult rats by blocking caspases, which are key components of apoptotic cell death. Multiple intracerebroventricular infusions of caspase inhibitors (pancaspase inhibitor zVADfmk, and caspase 3 and 9 inhibitor) prior to, just after, 1 day after, and 1 week following 2 h of lithium-pilocarpine-induced status epilepticus reduced the number of terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick-end labelled (TUNEL) cells and increased the number of bromodeoxyuridine (BrdU) -stained proliferated cells in the subgranular zone at 1 week. The caspase inhibitor-treated group did not differ from control at 2 days or 5 weeks following the epileptic insult. Our findings suggest that caspases modulate seizure-induced neurogenesis in the DG, probably by regulating apoptosis of newly born neurons, and that this action can be suppressed transiently by caspase inhibitors. Furthermore, although previous studies have indicated that increased neuronal death can trigger neurogenesis, we show here that reduction in apoptotic death may be associated with increased neurogenesis.
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| 17. |
- Ekdahl Clementson, Christine, et al.
(författare)
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Caspase-mediated death of newly formed neurons in the adult rat dentate gyrus following status epilepticus.
- 2002
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 16:8, s. 1463-1471
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Tidskriftsartikel (refereegranskat)abstract
- A large proportion of cells that proliferate in the adult dentate gyrus under normal conditions or in response to brain insults exhibit only short-term survival. Here, we sought to determine which cell death pathways are involved in the degeneration of newly formed neurons in the rat dentate gyrus following 2 h of electrically induced status epilepticus. We investigated the role of three families of cysteine proteases, caspases, calpains, and cathepsins, which can all participate in apoptotic cell death. Status epilepticus increased the number of bromodeoxyuridine (BrdU)-positive proliferated cells in the subgranular zone of the dentate gyrus. At the time of maximum cell proliferation, immunohistochemical analyses revealed protein expression of active caspase-cleaved poly (ADP-ribose) polymerase (PARP) in approximately 66% of the BrdU-positive cells, while none of them expressed cathepsin B or the 150-kDa calpain-produced fodrin breakdown product. To evaluate the importance of cysteine proteases in regulating survival of the newly formed neurons, we administered intracerebroventricular infusions of a caspase inhibitor cocktail (zVAD-fmk, zDEVD-fmk and zLEHD-fmk) over a 2-week period, sufficient to allow for neuronal differentiation, starting 1 week after the epileptic insult. Increased numbers of cells double-labelled with BrdU and neuron-specific nuclear protein (NeuN) marker were detected in the subgranular zone and granule cell layer of the caspase inhibitor-treated rats. Our data indicate that caspase-mediated cell death pathways are active in progenitor cell progeny generated by status epilepticus and compromise survival during neuronal differentiation.
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| 18. |
- Ericson, Cecilia, et al.
(författare)
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Ex vivo gene delivery of GDNF using primary astrocytes transduced with a lentiviral vector provides neuroprotection in a rat model of Parkinson's disease.
- 2005
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 22:11, s. 2755-2764
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Tidskriftsartikel (refereegranskat)abstract
- Astrocytes are, as normal constituents of the brain, promising vehicles for ex vivo gene delivery to the central nervous system. In the present study, we have used a lentiviral vector encoding glial cell line-derived neurotrophic factor (GDNF) to transduce rat-derived primary astrocytes, in order to evaluate their potential for long-term transgene expression in vivo and neuroprotection in a rat model of Parkinson's disease. Following transplantation of GDNF-transduced astrocytes to the intact striatum, the level of released GDNF was 2.93 +/- 0.28 ng/mg tissue at 1 week post-grafting, reduced to 0.42 +/- 0.12 ng/mg tissue at 4 weeks, and thereafter was maintained at this level throughout the experiment (12 weeks; 0.53 +/- 0.068 ng/mg tissue). Similarly, grafting to the substantia nigra (SN) resulted in a significant overexpression of GDNF ( approximately 0.20 ng/mg tissue) at 1 week. Intact animals receiving transplants of GDNF-transduced astrocytes displayed an increased contralateral turning (5.39 +/- 1.19 turns/min) in the amphetamine-induced rotation test, which significantly correlated with the GDNF tissue levels measured in the striatum, indicating a stimulatory effect of GDNF on the dopaminergic function. Transplantation of GDNF-transduced astrocytes to the SN 1 week prior to an intrastriatal 6-hydroxydopamine lesion provided a significant protection of nigral tyrosine hydroxylase-positive cells. By contrast, when the cells were transplanted to the striatum, the level of released GDNF was not sufficient to rescue the striatal fibers and, hence, to protect the nigral dopaminergic neurons. Overall, our results suggest that genetically modified astrocytes expressing GDNF can provide neuroprotection in a rat model of Parkinson's disease following transplantation to the SN.
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| 19. |
- Ferencz, Istvan, et al.
(författare)
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Suppression of kindling epileptogenesis in rats by intrahippocampal cholinergic grafts
- 1998
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 10:1, s. 213-220
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Tidskriftsartikel (refereegranskat)abstract
- Selective immunolesioning of the basal forebrain cholinergic system by 192 IgG-saporin, which leads to a dramatic loss of the cholinergic innervation in cortical and hippocampal regions, facilitates the development of hippocampal kindling in rats. The aim of the present study was to explore whether grafted cholinergic neurones are able to reverse the lesion-induced increase of seizure susceptibility. Intraventricular 192 IgG-saporin was administered to rats which 3 weeks later were implanted with rat embryonic, acetylcholine-rich septal-diagonal band tissue ('cholinergic grafts') or cortical tissue/vehicle ('sham grafts') bilaterally into the hippocampal formation. After 3 months, the grafted animals as well as non-lesioned control rats were subjected to daily hippocampal kindling stimulations. In the animals with cholinergic grafts, which had reinnervated the hippocampus and dentate gyrus bilaterally, there was a marked suppression of the development of seizures as compared with the hyperexcitable, sham-grafted rats. This effect was significantly correlated to the density of the graft-derived cholinergic innervation of the host hippocampal formation. The kindling rate in the rats with cholinergic grafts was similar to that in non-lesioned controls. These results provide further evidence that the intrinsic basal forebrain cholinergic system dampens kindling epileptogenesis and demonstrate that this function can be exerted also by grafted cholinergic neurones.
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| 20. |
- Fischer, Walter, et al.
(författare)
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Degenerative Changes in Forebrain Cholinergic Nuclei Correlate with Cognitive Impairments in Aged Rats
- 1989
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 1:1, s. 34-45
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Tidskriftsartikel (refereegranskat)abstract
- Degenerative changes in the forebrain cholinergic nuclei have been studied morphometrically in behaviourally characterized aged female Sprague-Dawley rats. In all regions analysed (medial septum, diagonal band of Broca, nucleus basalis, and striatum) the acetylcholinesterase-positive neurons were reduced in both size and number in the aged (24-months-old) rats as compared to the young (3-months-old) controls. The overall reduction in cell size amounted to between 20 and 30% and the overall reduction in cell number to between 27 and 45%. Impairment in learning and/or memory performance in the aged rats, as assessed in the Morris' water-maze task, was significantly correlated with both cholinergic cell size and cell number in the medial septum, and with cholinergic cell number in the diagonal band of Broca and in the striatum. In the nucleus basalis there was a trend in the same direction but it did not reach significance. In contrast to these degenerative changes in the cell body regions, no significant differences in cortical or hippocampal choline acetyltransferase activity were detected biochemically between the young and the aged rats, and the enzyme activity levels did not correlate with the degree of behavioural impairment in the aged rats. The present results provide evidence that all major forebrain cholinergic cell groups undergo degenerative changes with age in the rat, and that the most severe changes are found in those rats which display the most profound spatial learning impairments. Despite the severe changes at the cell body level, however, the choline acetyltransferase activity in the cortical projection areas are affected only to a minor degree, perhaps as a result of functional compensatory changes at the terminal level.
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| 21. |
- Fountaine, Timothy M., et al.
(författare)
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The effect of alpha-synuclein knockdown on MPP plus toxicity in models of human neurons
- 2008
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 28:12, s. 2459-2473
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Tidskriftsartikel (refereegranskat)abstract
- The protein alpha-synuclein is central to the pathophysiology of Parkinson's disease (PD) but its role in the development of neurodegeneration remains unclear. alpha-Synuclein-knockout mice develop without gross abnormality and are resistant to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a mitochondrial inhibitor widely used to model parkinsonism. Here we show that differentiated human dopaminergic neuron-like cells also have increased resistance to 1-methyl-4-phenylpyridine (MPP+), the active metabolite of MPTP, when alpha-synuclein is knocked down using RNA interference. In attempting to understand how this occurred we found that lowering alpha-synuclein levels caused changes to intracellular vesicles, dopamine transporter (DAT) and vesicular monoamine transporter (VMAT2), each of which is known to be an important component of the early events leading to MPP+ toxicity. Knockdown of alpha-synuclein reduced the availability of DAT on the neuronal surface by 50%, decreased the total number of intracellular vesicles by 37% but increased the density of VMAT2 molecules per vesicle by 2.8-fold. However, these changes were not associated with any reduction in MPP+-induced superoxide production, suggesting that alpha-synuclein knockdown may have other downstream effects which are important. We then showed that alpha-synuclein knockdown prevented MPP+-induced activation of nitric oxide synthase (NOS). Activation of NOS is an essential step in MPTP toxicity and increasing evidence points to nitrosative stress as being important in neurodegeneration. Overall, these results show that as well as having a number of effects on cellular events upstream of mitochondrial dysfunction alpha-synuclein affects pathways downstream of superoxide production, possibly involving regulation of NOS activity.
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| 22. |
- Fuentes, Romulo, et al.
(författare)
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Restoration of locomotive function in Parkinson's disease by spinal cord stimulation: mechanistic approach
- 2010
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 32:7, s. 1100-1108
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Tidskriftsartikel (refereegranskat)abstract
- Specific motor symptoms of Parkinson's disease (PD) can be treated effectively with direct electrical stimulation of deep nuclei in the brain. However, this is an invasive procedure, and the fraction of eligible patients is rather low according to currently used criteria. Spinal cord stimulation (SCS), a minimally invasive method, has more recently been proposed as a therapeutic approach to alleviate PD akinesia, in light of its proven ability to rescue locomotion in rodent models of PD. The mechanisms accounting for this effect are unknown but, from accumulated experience with the use of SCS in the management of chronic pain, it is known that the pathways most probably activated by SCS are the superficial fibers of the dorsal columns. We suggest that the prokinetic effect of SCS results from direct activation of ascending pathways reaching thalamic nuclei and the cerebral cortex. The afferent stimulation may, in addition, activate brainstem nuclei, contributing to the initiation of locomotion. On the basis of the striking change in the corticostriatal oscillatory mode of neuronal activity induced by SCS, we propose that, through activation of lemniscal and brainstem pathways, the locomotive increase is achieved by disruption of antikinetic low-frequency (< 30 Hz) oscillatory synchronization in the corticobasal ganglia circuits.
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| 23. |
- Gabery, Sanaz, et al.
(författare)
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Characterization of a rat model of Huntington's disease based on targeted expression of mutant huntingtin in the forebrain using adeno-associated viral vectors.
- 2012
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 36:6, s. 2789-2800
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Tidskriftsartikel (refereegranskat)abstract
- Huntington's disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin (htt) gene. Neuropathology is most severe in the striatum and cerebral cortex. As mutant htt is ubiquitously expressed, it has not been possible to establish clear structure-to-function relationships for the clinical aspects. In the present study, we have injected recombinant adeno-associated viral vectors of serotype 5 (rAAV5) expressing an 853-amino-acid fragment of htt with either 79 (mutant) or 18 (wild-type) glutamines (Q) in the dorsal striatum of neonatal rats to achieve expression of htt in the forebrain. Rats were followed for 6 months and compared with control rats. Neuropathological assessment showed long-term expression of the green fluorescent protein (GFP) transgene (used as a marker protein) and accumulation of htt inclusions in the cerebral cortex with the rAAV5-htt-79Q vectors. We estimated that around 10% of NeuN-positive cells in the cerebral cortex and 2% of DARPP-32 neurons in the striatum were targeted with the GFP-expressing vector. Formation of intracellular htt inclusions was not associated with neuronal loss, gliosis or microglia activation and did not lead to altered motor activity or changes in body weight. However, the same mutant htt vector caused orexin loss in the hypothalamus - another area known to be affected in HD. In conclusion, our results demonstrate that widespread forebrain expression of mutant htt can be achieved using rAAV5-vectors and suggest that this technique can be further explored to study region-specific effects of mutant htt or other disease-causing genes in the brain.
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| 24. |
- Garwicz, Martin, et al.
(författare)
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Distribution of Cutaneous Nociceptive and Tactile Climbing Fibre Input to Sagittal Zones in Cat Cerebellar Anterior Lobe
- 1992
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 4:4, s. 289-295
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Tidskriftsartikel (refereegranskat)abstract
- Climbing fibres projecting to the cerebellar C3 zone (and the related C1 and Y zones) receive spatially well organized tactile and nociceptive inputs from the skin. In the present study, cutaneous tactile and nociceptive input to climbing fibres projecting to the X, B, C2 and D1 zones in lobule V were investigated in pentobarbitone-anaesthetized cats. From the present results and previous studies, it is concluded that the X, C1, CX, C3 and Y zones receive cutaneous nociceptive climbing fibre input. By contrast, climbing fibres to the B, C2 and D1 zones lack cutaneous nociceptive input. Tactile input was found in all zones. The spatial organization of receptive fields of climbing fibres projecting to the X and D1 zones was similar to that in the C3 zone. They were located on the ipsilateral forelimb, mainly its lateral and distal parts, and their proximal borders were located close to joints. In the B zone, more than half of the receptive fields of climbing fibres were confined to the ipsilateral hind- or forelimb. However, frequently more than one limb and parts of the trunk were included. In the C2 zone, the majority of climbing fibres had distal ipsi- or bilateral receptive fields on the forelimbs, often also including the head/face. Some of the bilateral forelimb receptive fields additionally included the hindlimbs ipsi- or bilaterally. The results indicate that each zone has a characteristic set of climbing fibre receptive fields, which is probably related to its efferent control functions.
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| 25. |
- Garwicz, Martin, et al.
(författare)
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Micro-organization of olivocerebellar and corticonuclear connections of the paravermal cerebellum in the cat
- 1996
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 8:12, s. 2726-2738
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Tidskriftsartikel (refereegranskat)abstract
- The olivocerebellar and corticonuclear connections of the forelimb area of the paravermal medial C3 zone were studied in the cat using a combined electrophysiological and fluorescent tracer technique. During an initial operation under barbiturate anaesthesia, lobules IV/V of the cerebellar anterior lobe were exposed and small injections of dextran amines tagged with rhodamine or fluorescein were made into areas selected from four different electrophysiologically defined parts of the zone. The inferior olive and the deep cerebellar nuclei were then scrutinized for retrogradely labelled cells and anterogradely labelled axon terminals respectively. The findings demonstrate a detailed topographical organization within the olivocerebellar projection to the medial C3 zone and provide some evidence for a topographical organization of its projection to nucleus interpositus anterior. Both projections are described at a level of resolution not previously attained in neuroanatomical studies and the results strongly support the notion of a micro-compartmentalization of cerebellar olivo-corticonuclear circuits.
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