Nicotinic acetylcholine receptors mediate fast synaptic transmission in both central and peripheral nervous systems. These receptors play important roles in various physiological functions and are involved in different neurological diseases. A disruption in nicotinic receptor-mediated synaptic transmission due to the loss of nAChRs was detected in the brains of patients with Parkinson's disease and Alzheimer's disease. Although ciliary neurotrophic factor (CNTF) has been reported to promote the cholinergic properties by increasing the production and storage of acetylcholine, it is still unclear whether CNTF can enhance nicotinic synaptic neurotransmission. In this study, we found that CNTF dramatically enhanced the frequency and amplitude of nicotinic excitatory post-synaptic currents in rat superior cervical ganglion neurons maintained in a medium supplemented with nerve growth factor. Moreover, the number of neurons displaying nicotinic synaptic currents was also significantly increased by CNTF. These results suggest that CNTF could enhance nicotinic synaptic transmission via both presynaptic and postsynaptic mechanisms. The findings of this study reinforce the rationale for the usage of combinations of different neurotrophic factors for the therapy of neurodegenerative diseases.
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http://dx.doi.org/10.1002/jnr.22260 | DOI Listing |
Alzheimers Dement
December 2024
Johns Hopkins University School of Medicine, Baltimore, MD, USA
Background: Deficits in interneuron and cholinergic circuits are noted in AD pathology, yet the precise mechanisms of their contribution to cognitive decline in the disease remain elusive. Neuronal Pentraxin 2 (NPTX2), a sensitive marker for synaptic activity and AD progression, is an immediate early gene expressed by pyramidal neurons that functions at excitatory synapses on Parvalbumin interneurons (PV‐IN) to cluster AMPA receptors and strengthen circuit inhibition. NPTX2 is later shed from some synapses into the cerebrospinal fluid (CSF), where reduced NPTX2 levels inversely correlate with hippocampal volume and cognitive performance in individuals with AD/MCI.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Certara SimCyp, Berwyn, PA, USA
Background: While a number of recent anti‐amyloid antibodies demonstrated a robust reduction of amyloid biomarkers in clinical trials, the impact on functional improvement is much more variable. We hypothesize that this larger variability is driven by comedications, common genotype variants and underlying tau pathology.
Method: In a previously calibrated computational neuroscience model of ADAS‐Cog, we implemented the effect of soluble amyloid monomers and oligomers on glutamate and nicotinic AChR neurotransmission and the effect of intracellular tau oligomers on voltage‐gated Na and K+ channels and synaptic density.
Objectives: The current gold standard for immunofluorescent (IF) visualization of neuromuscular junctions (NMJs) in muscle utilizes frozen tissue sections with fluorescent conjugated antibodies to demarcate neurons and IF alpha-bungarotoxin (α-BTX) to demarcate motor endplates. Frozen tissue sectioning comes with inherent inescapable limitations, including cryosectioning artifact and limited sample shelf-life. However, a parallel approach to identify NMJs in paraffin-embedded tissue sections has not been previously described.
View Article and Find Full Text PDFJ Physiol
December 2024
Université Paris Cité, CNRS, ENS Paris Saclay, Centre Borelli UMR 9010, Paris, France.
Terminal Schwann cells (TSCs) are capable of regulating acetylcholine (ACh) release at the neuromuscular junction (NMJ). We have identified GABA as a gliotransmitter at mouse NMJs. When ACh activates α7 nicotinic ACh receptor (nAChRs) on TSCs, GABA is released and activates GABA receptors on the nerve terminal that subsequently reduce ACh release.
View Article and Find Full Text PDFCell Mol Life Sci
December 2024
Univ Angers, INSERM, CNRS, MITOVASC, Équipe CARME, SFR ICAT, F-49000 Angers, France.
Chronic elevated blood pressure impinges on the functioning of multiple organs and therefore harms body homeostasis. Elucidating the protective mechanisms whereby the organism copes with sustained or repetitive blood pressure rises is therefore a topical challenge. Here we address this issue in the adrenal medulla, the master neuroendocrine tissue involved in the secretion of catecholamines, influential hormones in blood pressure regulation.
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