Long‐term nucleus basalis cholinergic depletion induces attentional deficits and impacts cortical neurons and BDNF levels without affecting the NGF synthesis

Abstract

Basal forebrain cholinergic neurons (BFCNs) represent the main source of cholinergic innervation to the cortex and hippocampus and degenerate early in Alzheimer's disease (AD) progression. Phenotypic maintenance of BFCNs depends on levels of mature nerve growth factor (mNGF) and mature brain-derived neurotrophic factor (mBDNF), produced by target neurons and retrogradely transported to the cell body.

Cholinergic basal forebrain system degeneration underlies postural instability/gait difficulty and attention impairment in Parkinson's disease

“…The remarkable role of cBF in both attention and gait stability is extensively described in animal experiments [44] and in vivo studies [21,45,46]. The volume and gray matter density in cBF, especially the NBM, were associated with attentional function [45,46] One intriguing finding is that PIGD score significantly correlated with cBF FWf and cholinergic projection in the parietal region, but not with FWf in the fiber tract or cholinergic projection in the other regions.…”

“…A significant correlation between cBF degeneration and PIGD score was found in PD, which was mediated by attentional function. The remarkable role of cBF in both attention and gait stability is extensively described in animal experiments [44] and in vivo studies [21, 45, 46]. The volume and gray matter density in cBF, especially the NBM, were associated with attentional function [45, 46], step length and step velocity [47].…”

Recent advances in cholinergic mechanisms: A preface for the ISCM2022 special issue

“…These results may have clinical significance because they provide important insights into the underlying mechanisms that may contribute to individuals expressing the ApoE4 allele as a key genetic risk factor for late-onset AD (Rai et al, 2023). The study on basal forebrain cholinergic neurons (BFCNs) by Orciani et al (2022) reveals that long-lasting cholinergic deprivation negatively affects cognitive performance and reduces the levels of BDNF, GABAergic, and glutamatergic markers. Of special significance is that the longterm cholinergic component does not appear to affect the biosynthesis of nerve growth factor, as is the case in AD pathology, thus highlighting the important role of its regulation in the AD brain (Orciani et al, 2022).…”

“…The study on basal forebrain cholinergic neurons (BFCNs) by Orciani et al. (2022) reveals that long‐lasting cholinergic deprivation negatively affects cognitive performance and reduces the levels of BDNF, GABAergic, and glutamatergic markers. Of special significance is that the long‐term cholinergic component does not appear to affect the biosynthesis of nerve growth factor, as is the case in AD pathology, thus highlighting the important role of its regulation in the AD brain (Orciani et al., 2022).…”