Amyloid-β (Aβ) drives the synaptic impairment and dendritic spine loss characteristic of Alzheimer's disease (AD), but how Aβ affects actin cytoskeleton remains unknown contentious. The actin-binding protein, cofilin-1 (cof1), is a major regulator dynamics in spines, subject to phospho-regulation by multiple pathways, including Rho-associated protein kinase (ROCK) pathway. While cof1 implicated as driver synaptotoxicity early phases AD pathophysiology, questions remain about molecular...

The sequence of cellular dysfunctions in preclinical Alzheimer's disease must be understood if we are to plot new therapeutic routes. Hippocampal neuronal hyperactivity is one the earliest events occurring during stages both humans and mouse models. most common hypothesis describes amyloid-β accumulation as triggering factor but effects this cascade leading cognitive decline remain unclear. In mice, previously showed that amyloid-β-dependent TRPA1 channel activation triggers hippocampal...

Fluorescent staining of astrocytes without damaging or interfering with normal brain functions is essential for intravital microscopy studies. Current methods involved either transgenic mice local intracerebral injection sulforhodamine 101. Transgenic rat models rarely exist, and in mice, a backcross GFAP may be difficult. Local injections fluorescent dyes are invasive. Here, we propose non-invasive, specific ubiquitous method to stain vivo. This based on iv applicable rats from postnatal...

Excessive synaptic loss is thought to be one of the earliest events in Alzheimer's disease (AD). However, key mechanisms that maintain plasticity synapses during adulthood or initiate synapse dysfunction AD remain unknown. Recent studies suggest astrocytes contribute functional changes observed and play a major role but behavior involvement early phases remained largely undefined.We measure astrocytic calcium activity mouse CA1 hippocampus stratum radiatum both global population at single...

Gene transfer into muscle by electroporation with low-voltage and long-pulse (LV/LP, 100 V/50 msec) currents was shown to be more efficient than simple intramuscular DNA injection. Nevertheless, transgene expression declined from day 7 only reached 10% of the maximum 3 weeks after electroporation. We have optimized conditions including voltage, pulse number, amount injected luciferaseencoding plasmid in tibialis anterior muscle. Using high-voltage short-pulse (HV/SP, 900 V/100 mu sec)...

The substantia nigra pars reticulata (SNr) is a major output nucleus of the basal ganglia circuitry particularly sensitive to pathological dopamine depletion. Indeed, hyperactivity SNr neurons known be responsible for some motor disorders characteristic Parkinson's disease. neuronal processing dysfunction well understood but, paradoxically, role astrocytes in regulation activity has rarely been considered. We thus investigated influence disruption dopaminergic transmission on plastic changes...

Using a monoclonal antibody that recognizes specifically high polysialylated form of N-CAM (high PSA N-CAM), the temporal and spatial expression this molecule was studied in developing spinal cord neural crest derivatives mouse truncal region. Temporal analyzed on immunoblots dorsal root ganglia (DRGs) extracts microdissected at different developmental stages. Analysis ratio to total indicated sialylation desialylation are independently regulated from polypeptide chains N-CAM. Motoneurons,...

Abstract In spermatozoa, voltage‐dependent calcium channels (VDCC) have been involved in different cellular functions like acrosome reaction (AR) and sperm motility. Multiple types of VDCC are present their relative contribution is still a matter debate. Based mostly on pharmacological studies, low‐voltage‐activated (LVA‐CC), responsible the inward current spermatocytes, were described as essential for AR sperm. The development Ca V 3.1 or 3.2 null mice provided opportunity to evaluate...

Before synaptogenesis, early excitability implicating voltage-dependent and transmitter-activated channels is known to be crucial for neuronal development. We previously showed that preplate (PP) neurons of the mouse neocortex express functional Na + as embryonic day 12. In this study, we investigated role these in signaling during embryonic-day-13 mice, activation with veratridine induced a large Ca 2+ response throughout neocortex, even cell populations lack channel. This -dependent...

Spontaneous calcium activity can be detected in embryonic mouse cortical slices as fluorescence intensity variations, the presence of a fluorescent indicator. Current methods to detect and quantify these variations depend heavily on experimenters whose judgement may interfere with measurement. In present work, we developed new software called CalSignal for automatic detection tracking cellular bodies quantification spontaneous time-series confocal images. Analysis 28 neocortical revealed...

Alterations of excitatory synaptic function are the strongest correlate to pathologic disturbance cognitive ability observed in early stages Alzheimer9s disease (AD). This feature is driven by amyloid-β oligomers (Aβos) and propagates from neuron neuron. Here, we investigated mechanism which Aβos affect synapses how these alterations propagate surrounding healthy neurons. We used complementary techniques ranging electrophysiological recordings molecular biology confocal microscopy primary...

Summary We show that mouse neural crest cells cultured in a serum-deprived chemically defined medium on appropriate culture substrata can be induced to express neuronal phenotype. The uncommitted mesenchymal intermediate filament protein such as vimentin, but not the usual markers receptor sites for tetanus toxin or neurofilaments. In medium, neurofilaments characterized after few hours culture. Furthermore, these acquire tetrodotoxin-sensitive voltage-dependent Na+ channels and generate...

The substantia nigra pars reticulata (SNr) is a major output nucleus of the basal ganglia, delivering inhibitory efferents to relay nuclei thalamus. Pathological hyperactivity SNr neurons known be responsible for some motor disorders e.g. in Parkinson's disease. One way restore this pathological activity electrically stimulate one input, excitatory subthalamic (STN), which has emerged as an effective treatment parkinsonian patients. neuronal network and signal processing ganglia are well...

Summary In the embryonic brain, post‐mitotic cortical neurons migrate from their place of origin to final location. Various external factors such as hormones, neurotransmitters or peptides regulate migration. To date, however, only a few studies have investigated effects these on electrical properties newly formed neurons. The aim present study was determine whether glutamate and brain‐derived neurotrophic factor (BDNF), known neuronal cell migration, could modulate currents through...

Abstract Background The sequence of cellular dysfunctions in preclinical Alzheimer’s disease must be understood if we are to plot new therapeutic routes. Hippocampal neuronal hyperactivity is one the earliest events occurring during stages both humans and mouse models. most common hypothesis describes amyloid β accumulation as triggering factor but effects such cascade leading cognitive decline remain unclear. In mice, previously showed that β-dependent TRPA1 channel activation triggers...