ArticleMolecular neurodegeneration2010
Axotomy-induced neurotrophic withdrawal causes the loss of phenotypic differentiation and downregulation of NGF signalling, but not death of septal cholinergic neurons.
Article in Molecular neurodegeneration, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Dysregulation of neurotrophin expression in prefrontal cortex and nucleus basalis magnocellularis during and after adolescent intermittent ethanol exposure.Alcohol (Fayetteville, N.Y.) · 2024Article
- Neurotrophic Natural Products.Progress in the chemistry of organic natural products · 2024Article
- Central Facial Nervous System Biomolecules Involved in Peripheral Facial Nerve Injury Responses and Potential Therapeutic Strategies.Antioxidants (Basel, Switzerland) · 2023Review
- Neonatal ethanol causes profound reduction of cholinergic cell number in the basal forebrain of adult animals.Alcohol (Fayetteville, N.Y.) · 2021Article
- The many disguises of the signalling endosome.FEBS letters · 2018Review
- Article
- Exercise leads to the re-emergence of the cholinergic/nestin neuronal phenotype within the medial septum/diagonal band and subsequent rescue of both hippocampal ACh efflux and spatial behavior.Experimental neurology · 2016Article
- Chemogenetic Inactivation of Dorsal Anterior Cingulate Cortex Neurons Disrupts Attentional Behavior in Mouse.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Article
- Reversal of Neuronal Atrophy: Role of Cellular Immunity in Neuroplasticity and Aging.Journal of neurological disorders · 2014Article
- Loss of cholinergic phenotype in septohippocampal projection neurons: relation to brain versus peripheral IL-2 deficiency.Neuroscience letters · 2013Article
- Cholinergic abnormalities, endosomal alterations and up-regulation of nerve growth factor signaling in Niemann-Pick type C disease.Molecular neurodegeneration · 2012Article
- Transcription factor LIM homeobox 7 (Lhx7) maintains subtype identity of cholinergic interneurons in the mammalian striatum.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Article
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
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Abstract
backgroundSeptal cholinergic neurons account for most of the cholinergic innervations of the hippocampus, playing a key role in the regulation of hippocampal synaptic activity. Disruption of the septo-hippocampal pathway by an experimental transection of the fimbria-fornix drastically reduces the target-derived trophic support received by cholinergic septal neurons, mainly nerve growth factor (NGF) from the hippocampus. Axotomy of cholinergic neurons induces a reduction in the number of neurons positive for cholinergic markers in the medial septum. In several studies, the reduction of cholinergic markers has been interpreted as analogous to the neurodegeneration of cholinergic cells, ruling out the possibility that neurons lose their cholinergic phenotype without dying. Understanding the mechanism of cholinergic neurodegeneration after axotomy is relevant, since this paradigm has been extensively explored as an animal model of the cholinergic impairment observed in neuropathologies such as Alzheimer's disease.The principal aim of this study was to evaluate, using modern quantitative confocal microscopy, neurodegenerative changes in septal cholinergic neurons after axotomy and to assess their response to delayed infusion of NGF in rats.
resultsWe found that there is a slow reduction of cholinergic cells labeled by ChAT and p75 after axotomy. However, this phenomenon is not accompanied by neurodegenerative changes or by a decrease in total neuronal number in the medial septum. Although the remaining axotomized-neurons appear healthy, they are unable to respond to delayed NGF infusion.
conclusionsOur results demonstrate that at 3 weeks, axotomized cholinergic neurons lose their cholinergic phenotype without dying and down-regulate their NGF-receptors, precluding the possibility of a response to NGF. Therefore, the physiological role of NGF in the adult septal cholinergic system is to support phenotypic differentiation and not survival of neurons. This evidence raises questions about the relationship between transcriptional regulation of the cholinergic phenotype by retrograde-derived trophic signaling and the transcriptional changes experienced when retrograde transport is impaired due to neuropathological conditions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.