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| 2. |
- Bakalkin, Georgy, et al.
(author)
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Coordinated expression of the renin-angiotensin genes in the lumbar spinal cord : Lateralization and effects of unilateral brain injury
- 2021
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In: European Journal of Neuroscience. - : John Wiley & Sons. - 0953-816X .- 1460-9568. ; 54:4, s. 5560-5573
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Journal article (peer-reviewed)abstract
- In spite of its apparent symmetry, the spinal cord is asymmetric in its reflexes and gene expression patterns including leftward expression bias of the opioid and glutamate genes. To examine whether this is a general phenomenon for neurotransmitter and neurohormonal genes, we here characterized expression and co-expression (transcriptionally coordinated) patterns of genes of the renin-angiotensin system (RAS) that is involved in neuroprotection and pathological neuroplasticity in the left and right lumbar spinal cord. We also tested whether the RAS expression patterns were affected by unilateral brain injury (UBI) that rewired lumbar spinal neurocircuits. The left and right halves of the lumbar spinal cord were analysed in intact rats, and rats with left- or right-sided unilateral cortical injury, and left- or right-sided sham surgery. The findings were (i) lateralized expression of the RAS genes Ace, Agtr2 and Ren with higher levels on the left side; (ii) the asymmetry in coordination of the RAS gene expression that was stronger on the right side; (iii) the decay in coordination of co-expression of the RAS and neuroplasticity-related genes induced by the right-side but not left-side sham surgery and UBI; and (iv) the UBI-induced shift to negative regulatory interactions between RAS and neuroplasticity-related genes on the contralesional spinal side. Thus, the RAS genes may be a part of lateralized gene co-expression networks and have a role in a side-specific regulation of spinal neurocircuits.
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| 3. |
- Bazzurro, V., et al.
(author)
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Involvement of GABA(A) receptors containing alpha(6) subtypes in antisecretory factor activity on rat cerebellar granule cells studied by two-photon uncaging
- 2022
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In: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 56:5, s. 4505-4513
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Journal article (peer-reviewed)abstract
- The antisecretory factor (AF) is an endogenous protein that counteracts intestinal hypersecretion and various inflammation conditions in vivo. It has been detected in many mammalian tissues and plasma, but its mechanisms of action are largely unknown. To study the pharmacological action of the AF on different GABA(A) receptor populations in cerebellar granule cells, we took advantage of the two-photon uncaging method as this technique allows to stimulate the cell locally in well-identified plasma membrane parts. We compared the electrophysiological response evoked by releasing a caged GABA compound on the soma, the axon initial segment and neurites before and after administering AF-16, a 16 amino acids long peptide obtained from the amino-terminal end of the AF protein. After the treatment with AF-16, we observed peak current increases of varying magnitude depending on the neuronal region. Thus, studying the effects of furosemide and AF-16 on the electrophysiological behaviour of cerebellar granules, we suggest that GABA(A) receptors, containing the alpha(6) subunit, may be specifically involved in the increase of the peak current by AF, and different receptor subtype distribution may be responsible for differences in this increase on the cell.
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| 4. |
- Binder, Luisa B., et al.
(author)
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Neuro-immune interactions in health and disease: Insights from FENS-Hertie 2022 Winter School
- 2024
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In: European Journal of Neuroscience. - : WILEY. - 0953-816X .- 1460-9568.
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Journal article (other academic/artistic)abstract
- In a great partnership, the Federation of European Neuroscience Societies (FENS) and the Hertie Foundation organized the FENS-Hertie 2022 Winter School on 'Neuro-immune interactions in health and disease'. The school selected 27 PhD students and 13 postdoctoral fellows from 20 countries and involved 14 faculty members experts in the field. The Winter School focused on a rising field of research, the interactions between the nervous and both innate and adaptive immune systems under pathological and physiological conditions. A fine-tuned neuro-immune crosstalk is fundamental for healthy development, while disrupted neuro-immune communication might play a role in neurodegeneration, neuroinflammation and aging. However, much is yet to be understood about the underlying mechanisms of these neuro-immune interactions in the healthy brain and under pathological scenarios. In addition to new findings in this emerging field, novel methodologies and animal models were presented to foment research on neuro-immunology. The FENS-Hertie 2022 Winter School provided an insightful knowledge exchange between students and faculty focusing on the latest discoveries in the biology of neuro-immune interactions while fostering great academic and professional opportunities for early-career neuroscientists from around the world.
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| 5. |
- Carvalho, Liliana S., et al.
(author)
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Unilateral brain injury to pregnant rats induces asymmetric neurological deficits in the offspring
- 2021
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In: European Journal of Neuroscience. - : John Wiley & Sons. - 0953-816X .- 1460-9568. ; 53:11, s. 3621-3633
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Journal article (peer-reviewed)abstract
- Effects of environmental factors may be transmitted to the following generation, and cause neuropsychiatric disorders including depression, anxiety, and posttraumatic stress disorder in the offspring. Enhanced synaptic plasticity induced by environmental enrichment may be also transmitted. We here test the hypothesis that the effects of brain injury in pregnant animals may produce neurological deficits in the offspring. Unilateral brain injury (UBI) by ablation of the hindlimb sensorimotor cortex in pregnant rats resulted in the development of hindlimb postural asymmetry (HL-PA), and impairment of balance and coordination in beam walking test in the offspring. The offspring of rats with the left UBI exhibited HL-PA before and after spinal cord transection with the contralesional (i.e., right) hindlimb flexion. The right UBI caused the offspring to develop HL-PA that however was cryptic and not-lateralized; it was evident only after spinalization, and was characterized by similar occurrence of the ipsi- and contralesional hindlimb flexion. The HL-PA persisted after spinalization suggesting that the asymmetry was encoded in lumbar spinal neurocircuits that control hindlimb muscles. Balance and coordination were affected by the right UBI but not the left UBI. Thus, the effects of a unilateral brain lesion in pregnant animals may be intergenerationally transmitted, and this process may depend on the side of brain injury. The results suggest the existence of left-right side-specific mechanisms that mediate transmission of the lateralized effects of brain trauma from mother to fetus.
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| 7. |
- Estévez-Silva, Héctor M., et al.
(author)
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Pridopidine modifies disease phenotype in a SOD1 mouse model of amyotrophic lateral sclerosis
- 2022
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In: European Journal of Neuroscience. - : John Wiley & Sons. - 0953-816X .- 1460-9568. ; 55:5, s. 1356-1372
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Journal article (peer-reviewed)abstract
- Amyotrophic lateral sclerosis (ALS) is a lethal and incurable neurodegenerative disease due to the loss of upper and lower motor neurons, which leads to muscle weakness, atrophy, and paralysis. Sigma-1 receptor (σ-1R) is a ligand-operated protein that exhibits pro-survival and anti-apoptotic properties. In addition, mutations in its codifying gene are linked to development of juvenile ALS pointing to an important role in ALS. Here, we investigated the disease-modifying effects of pridopidine, a σ-1R agonist, using a delayed onset SOD1 G93A mouse model of ALS. Mice were administered a continuous release of pridopidine (3.0 mg/kg/day) for 4 weeks starting before the appearance of any sign of muscle weakness. Mice were monitored weekly and several behavioural tests were used to evaluate muscle strength, motor coordination and gait patterns. Pridopidine-treated SOD1 G93A mice showed genotype-specific effects with the prevention of cachexia. In addition, these effects exhibited significant improvement of motor behaviour 5 weeks after treatment ended. However, the survival of the animals was not extended. In summary, these results show that pridopidine can modify the disease phenotype of ALS-associated cachexia and motor deficits in a SOD1 G93A mouse model.
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| 8. |
- Fischi-Gomez, E., et al.
(author)
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Ultrahigh field in vivo characterization of microstructural abnormalities in the orbitofrontal cortex and amygdala in autism
- 2021
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In: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 54:6, s. 6229-6236
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Journal article (peer-reviewed)abstract
- There are currently no biomarkers for autism spectrum disorder (ASD). This neurodevelopmental condition has previously been associated with histopathological findings, including increased neuronal packing density in the amygdala, abnormal laminar cytoarchitecture and increased average neuronal density in the prefrontal cortex. The present study examined whether new brain imaging technologies could reveal in vivo, in adults with ASD, the manifestation of previously described histopathological changes. Using quantitative mapping at ultrahigh field (7 Tesla), we show that we can observe microstructural alterations in the right lateral orbitofrontal cortex and the bilateral amygdala in adult individuals with ASD in vivo. These imaging alterations point to an abnormal laminar cytoarchitecture and to an increased neuronal density, similar to what has been previously described in post-mortem data in ASD. Our data demonstrate that it is possible to visualize, in vivo and at the individual level, alterations of cortical and subcortical microstructure in ASD. Future studies will be needed to extend these findings to a larger group of individuals and evaluate their association with symptomatology as well as their specificity among the different neurodevelopmental disorders.
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| 9. |
- Frost Nylén, J, et al.
(author)
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Reciprocal interaction between striatal cholinergic and low-threshold spiking interneurons - A computational study
- 2020
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In: European Journal of Neuroscience. - : Blackwell Publishing Ltd. - 0953-816X .- 1460-9568.
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Journal article (peer-reviewed)abstract
- The striatum is the main input stage of the basal ganglia receiving extrinsic input from cortex and thalamus. The striatal projection neurons (SPN) constitute 95% of the neurons in the striatum in mice while the remaining 5% are cholinergic and GABAergic interneurons. The cholinergic (ChIN) and low-threshold spiking interneurons (LTS) are spontaneously active and form a striatal subnetwork involved in salience detection and goal-directed learning. Activation of ChINs has been shown to inhibit LTS via muscarinic receptor type 4 (M4R) and LTS in turn can modulate ChINs via nitric oxide (NO) causing a prolonged depolarization. Thalamic input prefentially excites ChINs, whereas input from motor cortex favours LTS, but can also excite ChINs. This varying extrinsic input with intrinsic reciprocal, yet opposing, effects raises the possibility of a slow input-dependent modulatory subnetwork. Here, we simulate this subnetwork using multicompartmental neuron models that incorporate data regarding known ion channels and detailed morphological reconstructions. The modelled connections replicate the experimental data on muscarinic (M4R) and nitric oxide modulation onto LTS and ChIN, respectively, and capture their physiological interaction. Finally, we show that the cortical and thalamic inputs triggering the opposing modulation within the network induce periods of increased and decreased spiking activity in ChINs and LTS. This could provide different temporal windows for selective modulation by acetylcholine and nitric oxide, and the possibility of interaction with the wider striatal microcircuit.
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| 10. |
- Gregory, S., et al.
(author)
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Self-reported diabetes is associated with allocentric spatial processing in the European Prevention of Alzheimer's Dementia Longitudinal Cohort Study
- 2022
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In: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 56:10, s. 5917-5930
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Journal article (peer-reviewed)abstract
- Type 2 diabetes is a robust predictor of cognitive impairment. Impairment in allocentric processing may help identify those at increased risk for Alzheimer's disease dementia. The objective of this study was to investigate the performance of participants with and without diabetes on a task of allocentric spatial processing. This was a cross-sectional secondary data analysis study using baseline data from the European Prevention of Alzheimer's Dementia Longitudinal Cohort Study (EPAD LCS). Participants were aged 50 years and above and were free of dementia at baseline. Participants with no missing data on the variables of interest were included in this study. Our exposure variable was diabetes reported in the medical history. Our primary outcome was the Four Mountains Test (4MT), a novel task of allocentric processing. Covariates included demographics (age, sex, family history of dementia and years of education), APOE epsilon 4 carrier status, cognitive status (Clinical Dementia Rating scale), cerebrospinal fluid phosphorylated tau and amyloid-beta 1-42. Of 1324 participants (mean age = 65.95 (+/- 7.45)), 90 had diabetes. Participants with diabetes scored 8.32 (+/- 2.32) on the 4MT compared with 9.24 (+/- 2.60) for participants without diabetes. In a univariate model, diabetes was significantly associated with worse 4MT total scores (beta = -.92, p = .001), remaining significant in a fully adjusted model (beta = -.64, p = .01). Cerebrospinal fluid phosphorylated tau was significantly higher in participants with diabetes compared with those without. Novel cognitive tests, such as the 4MT, may be appropriate to identify early cognitive changes in this high-risk group. Identifying those at greatest risk for future neurodegeneration is key to prevention efforts.
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