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vGLUT1

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Pregnant women at risk of premature labor receive a single treatment with the synthetic glucocorticoid dexamethasone (DEX) between the 24th and 34th week of pregnancy to ensure adequate maturation of the fetal organs. Due to the postponement of the due date, several doses are often administered. Because purinergic signaling plays an important role in the development of the auditory brainstem, particularly the cochlear nucleus, we investigated whether repeated DEX treatments affect components of the ADP-mediated (NTPDase2 and P2Y1R) and adenosinergic (CD73 and A1R) signaling systems. To compare

Neuroscience

Differences in the synaptic function of human and murine alpha-synuclein

Jen Riba, Alexandra Stavsky, Daniel Gitler · FENS Forum 2024

Alpha-synuclein (α-syn) is an abundant presynaptic protein that associates with the surface of synaptic vesicles (SVs). It is the main component of Lewy bodies, abnormal protein aggregates that serve as a hallmark of both sporadic and familial forms of Parkinson's disease (PD). While its physiological role in the synapse remains elusive, recent studies indicate it attenuates synaptic transmission and regulates SV clustering. Specifically, when human α-syn (h-α-syn) is over-expressed in mouse neurons by viral transduction or in transgenic mice, it inhibits SV recycling and disperses the SV clus

Neuroscience

The DPYSL5 (Dihydropyrimidinase like 5) gene encodes a cytosolic protein which regulates axonal guidance and neuritic growth. We initially described two missense mutations (p.Glu41Lys, recurrent ; p.Gly47Arg) in DPYSL5 gene in nine individuals presenting intellectual disability and agenesis of the corpus callosum. Interestingly, both variants caused abnormal neuronal development and impaired interaction between DPYSL5 and MAP2 and TUBB3 proteins. Recently, a third de novo variant (p.Glu25Lys) was identified in four individuals with a similar clinical phenotype. Various studies described DPYSL5

Neuroscience

Tetanus Neurotoxin (TeNT) enters the peripheral endings of motor axons in muscles and transports to motoneuron cell bodies where transynaptically translocates to presynaptic inputs blocking inhibitory synapses. This disinhibits motoneurons causing dysregulated firing and tetanic contractions. Preferential actions on inhibitory synapses are usually explained by enrichment in the Vesicle-Associated Membrane Protein 2 isoform (VAMP2). VAMP1 and VAMP2 form part of the SNARE complex and are differentially distributed in different synapses. Nevertheless, the exact VAMP content inside synapses on mot

Neuroscience

Alzheimer’s Disease (AD) is a progressive neurological disorder that gradually deteriorates cognitive abilities and leads to the inability to carry out simple tasks. However, the molecular mechanisms and causes of this disease are still unclear. This research aims to use the proteomic signature of the 5xFAD AD mouse model to identify early changes in protein expression in the AD brain compared to the wild type. Lysates from the cerebral cortex of 3 months-old 5xFAD and wild-type mice were analysed by LC-MS/MS and investigated for protein candidates over- or under- expressed in AD mice compared

Molecular Neuroscience

Maternal high-fat diet (mHFD) during pregnancy leads to increased inflammation and oxidative stress, representing an important risk factor for fetal neurodevelopment. We have previously shown, in a mouse model of mHFD, sex-dimorphic negative outcomes in the adolescent offspring, disrupting hippocampal Bdnf-Nrf-2 crosstalk specifically in females. In this study, we hypothesize that sex-differences are still present during adulthood, affecting cognition and neurotransmission. Furthermore, we tested a maternal dietary supplementation with the antioxidant N-acetyl-cysteine (NAC) as a preventive st

Neuroscience

Immunoglobulin superfamily member 9b (IgSF9b) is a cell adhesion protein that has been linked to the etiology of several psychiatric disorders, including bipolar disorder and schizophrenia. Based on previous studies in neuronal cultures, IgSF9b was proposed to specifically regulate the structure and function of GABAergic synapses in the brain through an indirect interaction with the synaptic adhesion protein Neuroligin-2. To date, however, very little is known about the expression pattern of IgSF9b in the intact brain, and the synaptic localization of IgSF9b in different brain regions has neve

Neuroscience

Organization of excitatory afferents in the anterior part of the human thalamus

László Acsády, András Salma, Mengxing Liu et al. · FENS Forum 2024

The activity of thalamocortical neurons is largely defined by their excitatory inputs. The key determinants of excitatory afferents are the origin, complexity, and density of axon terminals. While some quantitative data are available on these aspects of glutamatergic afferents in animals, organization of excitatory inputs is unknown in the human thalamus. In this study we determined the origin, size and density of glutamatergic axon terminals in the anterior part of the human thalamus, examined their inter- and intra-nuclear heterogeneity as well and s the interindividual variability. We used

Neuroscience

Using immuno-electron microscopic methods (FIBSEM-TEM) we have previously reported PACAPergic calyceal axon terminals in the ventro-lateral capsular subdivision of the central amygdala (FENS abstract 2020, 2022) in rat. To further investigate the origin and molecular constituents of these peculiar calyceal terminals, we used fluorogold retrograde and AAV5-EF1a-DIO-hChR2(H134R)-eYFP anterograde tracing in Adcyap1-2A-cre mice and investigated its molecular signature for both presynaptic and postsynaptic components. We report here that this Calyx of Held-like giant synapse terminal has mixed glut

Neuroscience