| 1. |
- Ferencz, Istvan, et al.
(författare)
-
Suppression of kindling epileptogenesis in rats by intrahippocampal cholinergic grafts
- 1998
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 10:1, s. 213-220
-
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.
|
|
| 2. |
- Garwicz, Martin, et al.
(författare)
-
Micro-organization of olivocerebellar and corticonuclear connections of the paravermal cerebellum in the cat
- 1996
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 8:12, s. 2726-2738
-
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.
|
|
| 3. |
- Jörntell, Henrik, et al.
(författare)
-
Relation between cutaneous receptive fields and muscle afferent input to climbing fibres projecting to the cerebellar C3 zone in the cat
- 1996
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 8:8, s. 1769-1779
-
Tidskriftsartikel (refereegranskat)abstract
- Inferior olivary cells projecting as climbing fibres to the forelimb area of the cerebellar C3 zone were investigated with respect to their cutaneous and muscle afferent input in barbiturate-anaesthetized cats. Climbing fibre responses were recorded from single cerebellar cortical Purkinje cells on natural stimulation of the skin and on electrical stimulation of nerves to m. biceps brachii, m. triceps brachii and to nine muscles acting as dorsal or palmar flexors of the paw (and, in some cases, the digits). The analysis was focused on the functional organization of convergence between cutaneous and muscle afferents onto single olivary neurons. Cutaneous receptive fields on the dorsal side of the paw and on the digits were generally associated with moderate to strong input from dorsal flexors, but little or no input from palmar flexors or proximal muscles. Receptive fields on the ventral side of the paw and forearm were associated with relatively strong input from biceps and palmar flexors. Climbing fibres with cutaneous receptive fields extending on the ulnar side of the paw and forearm usually received strong input from the triceps and moderate to strong input from dorsal flexors, whereas input from the palmar flexors was weak or lacking. In conclusion, the results indicate that the cutaneous receptive fields in many cases are associated with input from muscles the action of which would tend to move the receptive field towards a stimulus applied to the skin.
|
|
| 4. |
- Kamme, Fredrik, et al.
(författare)
-
Biphasic Expression of the Fos and Jun Families of Transcription Factors Following Transient Forebrain Ischaemia in the Rat. Effect of Hypothermia
- 1995
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 7:10, s. 2007-2016
-
Tidskriftsartikel (refereegranskat)abstract
- Transient global ischaemia induces the expression of immediate early genes. Using in situ hybridization, the expression of c‐fos, fosB, fra‐1, fra‐2, c‐jun and junB was studied after 15 min of normothermic and hypothermia (33°C) transient forebrain ischaemia in the rat, induced by common carotid occlusion combined with systemic hypotension. Two phases of induction of the immediate early genes were observed. The early phase, peaking at 1–2 h of reperfusion, was dominated by marked expression in the dentate gyrus. The second phase, with maximal expression at 12–36 h of reperfusion, was observed particularly in the vulnerable CA1 and CA3 regions. Hypothermia increased the early induction of one of the genes studied, signifying a differential effect of hypothermia upon the signal transduction mechanisms activating these genes. The late induction occurred earlier after hypothermic than after normothermic ischaemia. The early expression of immediate early genes is due to the rapid activation of cytosolic response elements caused by the ischaemic insult. We suggest that the late induction is a stress signal for activation of repair processes, analogous to the cellular response seen after UV light‐induced DMA damage. The relatively fast induction of the immediate early genes following hypothermic ischaemia may reflect a faster resumption of normal intracellular signalling, enhancing neuronal recovery.
|
|
| 5. |
- Leanza, G, et al.
(författare)
-
Selective immunolesioning of the basal forebrain cholinergic system disrupts short-term memory in rats
- 1996
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 8:7, s. 1535-4154
-
Tidskriftsartikel (refereegranskat)abstract
- Selective depletion of nerve growth factor receptor-bearing neurons in the basal forebrain cholinergic system nuclei by the immunotoxin 192 IgG-saporin offers a new and highly useful tool for the study of the role of the forebrain cholinergic system in cognitive functions. In the present study, we have tested the effects of 192 IpG-saporin in an operant delayed matching-to-position task which has previously been used to discriminate between delay-dependent learning impairments and delay-independent disturbances of non-mnemonic processes. Rats were first trained to criterion performance and then received intraventricular injections of 5 microg of 192 IgG-saporin 4 weeks prior to a second testing session. Rats with 192 IgG-saporin lesions displayed a significant delay-dependent decline in performance compared to normal controls, indicating a deficit in short-term memory. Administration of the muscarinic blocker scopolamine (0.5 mg/kg, i.p.) produced more pronounced impairment in the performance of the normal control rats across all delays, and induced further impairment also in animals with 192 IgG-saporin lesions. These effects were not observed following control injections of methyl scopolamine, suggesting that the impairment induced by scopolamine was due to the blockade of central muscarinic receptors. No improvement in performance was observed in either group following systemic treatment with the muscarinic cholinergic agonist arecoline (1.00 mg/kg). Biochemical and morphological analyses confirmed the selective and severe (>90-95%) depletion of cholinergic neurons throughout the septal-diagonal band area and the nucleus basalis region by the intraventricular 192 IgG-saporin treatment. Although the immunotoxin was observed to produce additional damage to the cerebellar Purkinje cells, no gross motor abnormalities were observed that could contribute to the effects on accuracy in the task used here. In conclusion, the results show that selective combined lesions of the basal forebrain cholinergic neurons in the septal-diagonal band area and nucleus basalis produce long-lasting impairments in short-term memory, thus providing further support for a role of this system in cognitive functions.
|
|
| 6. |
- Leanza, G, et al.
(författare)
-
Selective lesioning of the basal forebrain cholinergic system by intraventricular 192 IgG-saporin : behavioural, biochemical and stereological studies in the rat
- 1995
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 7:2, s. 329-343
-
Tidskriftsartikel (refereegranskat)abstract
- The elucidation of the functional role of the basal forebrain cholinergic system will require access to a highly specific and efficient cholinergic neurotoxin. Recently, selective depletion of the nerve growth factor (NGF) receptor-bearing cholinergic neurons in the rat basal forebrain and a dramatic loss of cholinergic innervation in the related cortical regions have been obtained following intraventricular injection of a newly introduced immunotoxin, 192 IgG-saporin. Here we extend these initial findings and report that administration of increasing doses (1.25, 2.5, 5.0 or 10 micrograms) of the 192 IgG-saporin conjugate into the lateral ventricles of adult rats induced dose-dependent impairments in the water maze task and passive avoidance retention, but only weak and inconsistent effects on locomotor activity. These behavioural changes were paralleled by a reduction in choline acetyltransferase activity in hippocampus and several cortical areas (up to 97%) and selective depletions of NGF receptor-positive cholinergic neurons in the septal-diagonal band area and nucleus basalis magnocellularis (up to 99%). By contrast, the non-cholinergic parvalbumin-containing neurons in the septum were completely spared, and other cholinergic projection systems (such as in the striatum, thalamus, brainstem and spinal cord) were unaffected even at the highest dose. The observed changes in the water maze and passive avoidance tasks, as well as the cholinergic cell loss, were maintained up to at least 8 months following the intraventricular injection of a single dose (5 micrograms) of the immunotoxin. The results confirm the usefulness of the 192 IgG-saporin toxin for selective and profound lesions of the basal forebrain cholinergic neurons and provide further support for a role of the basal forebrain cholinergic system in cognitive functions.
|
|
| 7. |
- Remgård, Pär, et al.
(författare)
-
Calmodulin and In Vitro Regenerating Frog Sciatic Nerves : Release and Extracellular Effects
- 1995
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 7:6, s. 1386-1392
-
Tidskriftsartikel (refereegranskat)abstract
- Although calmodulin (CaM) is commonly considered to be an intracellular protein, it has been suggested lately that it is released and exerts functions extracellularly. In the present investigation this was studied in in vitro regenerating adult frog (Rana temporaria) sciatic nerves. Using a multi‐compartment incubation chamber, the non‐neuronal cells in the outgrowth region of such nerves were radiolabelled with amino acid precursors. Based on immunological criteria, these cells were shown to release CaM. When the nerves were treated with CaM, both the outgrowth of sensory axons and the injury‐induced proliferation of non‐neuronal cells were partially inhibited. The inhibitory effects occurred even when the incubation medium contained as little as 30 pM CaM. Furthermore, treatment with anti‐CaM antibodies resulted in reduced outgrowth, which suggested that during normal conditions extracellular CaM is kept at an optimal concentration. Finally, conditioned medium was found to contain several CaM‐binding proteins. The present findings may reflect an earlier unknown function of extracellular CaM in controlling various growth mechanisms in integrated tissues.
|
|
| 8. |
- Amandusson, Åsa, et al.
(författare)
-
Colocalization of oestrogen receptor immunoreactivity and preproenkephalin mRNA expression fo neurons in the superficial laminae of the spinal and medullary dorsal horn of rats
- 1996
-
Ingår i: Eur J Neurosci. - : Wiley InterScience. ; 8:11, s. 2440-2445
-
Tidskriftsartikel (refereegranskat)abstract
- A double-labelling procedure combining immunohistochemical staining with in situ hybridization using a radiolabelled cRNA probe was employed to demonstrate oestrogen receptor-like immunoreactivity and preproenkephalin-A mRNA in the medullary and spinal dorsal horn of female rats. Both markers labelled large numbers of neurons in the substantia gelatinosa and its trigeminal homologue. Many of these neurons were double-labelled, displaying both oestrogen receptor-like-immunoreactivity and preproenkephalin-A mRNA; cell counts showed that 40-60% of the of the oestrogen receptor-like-immunoreactive cells in the superficial laminae also were labelled for preproenkephalin-A mRNA, and that 60-70% of the preproenkephalin-A mRNA-labelled neurons in the same laminae displayed oestrogen receptor-like immunoreactivity. Previous studies have shown that oestrogen receptors can bind to the promoter region of the preproenkephalin-A gene, and studies on the hypothalamus have demonstrated that oestrogen regulates enkephalin expression in select neuronal populations. The present results demonstrate that enkephalinergic neurons in the superficial dorsal horn contain oestrogen receptors and suggest that oestrogen may play an important role in the modulation of sensory and nociceptive processing in the lower medulla and spinal cord.
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Korhonen, Laura, et al.
(författare)
-
Bcl-2 regulates the levels of the cysteine proteases ICH and CPP32/Yama in human neuronal precursor cells
- 1997
-
Ingår i: European Journal of Neuroscience. - Univ Uppsala, Ctr Biomed, Dept Dev Neurosci, S-75123 Uppsala, Sweden. : Wiley-Blackwell Publishing Inc.. - 0953-816X .- 1460-9568. ; 9:11, s. 2489-2496
-
Tidskriftsartikel (refereegranskat)abstract
- Members of the Bcl‐2 family are major regulators of cell death and survival. Bcl‐2 has been shown to heterodimerize with the death‐inducing protein Bax, but the mechanism of action of Bcl‐2 is not fully understood. Here we show, using the human NT‐2 neuronal cell line, that overexpression of Bcl‐2 leads to dramatic down‐regulation of the cysteine proteases ICH and CPP32/Yama, which are directly involved in cell death. In addition, the nuclear enzyme poly(ADP‐ribose) polymerase was cleaved in control cells but not in cells overexpressing Bcl‐2 following induction of apoptosis. The mRNA levels of ICH and CPP32/Yama were differentially affected by Bcl‐2 overexpression, suggesting both transcriptional and post‐transcriptional effects of the protein. These results demonstrate novel mechanisms of action of Bcl‐2 in influencing the expression of death effectors such as the cysteine proteases. The relative levels of Bcl‐2 and of various cysteine proteases ultimately determine survival and death of different cells, including neurons.
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
