AI Article Synopsis
Article Abstract
Patients with Alzheimer's disease (AD) display altered functioning of cortical networks, including altered patterns of synchronous activity and a serious deficit in cholinergic septohippocampal (SH) innervation. However, the mechanisms underlying these alterations and the implication of the GABAergic SH component in AD are largely unknown. In addition, the GABAergic septohippocampal pathway (SHP) is believed to regulate synchronous hippocampal activity by controlling the activity of interneurons. Here we show, using well-characterized pathway tracing experiments, that innervation of the GABAergic SHP decreases during normal aging. Furthermore, in an AD mouse model (hAPP(Sw,Ind); J20 mice), the GABAergic SHP shows a dramatic and early onset of this decrease in 8-mo-old mice. This decline is not caused by neuronal loss, but by the reduced number and complexity of GABAergic SH axon terminals. Finally, we demonstrate that hippocampal θ and γ rhythm power spectra are markedly diminished in 8-mo-old behaving mice expressing mutated hAPP. In addition to the well-known loss of cholinergic input to the hippocampus in AD, these data suggest that the altered patterns of synchronous activity seen in patients with AD could be caused by the loss of GABAergic SH axons, which modulate hippocampal network activities.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1096/fj.12-208413 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Selective Medial Septum Lesions in Healthy Rats Induce Longitudinal Changes in Microstructure of Limbic Regions, Behavioral Alterations, and Increased Susceptibility to Status Epilepticus.
Mol Neurobiol
October 2024
Departamento de Neurobiologia Conductual y Cognitiva, Instituto de Neurobiologia, Universidad Nacional Autonoma de Mexico, Campus UNAM-Juriquilla, 76230, Queretaro, Mexico.
Septo-hippocampal pathway, crucial for physiological functions and involved in epilepsy. Clinical monitoring during epileptogenesis is complicated. We aim to evaluate tissue changes after lesioning the medial septum (MS) of normal rats and assess how the depletion of specific neuronal populations alters the animals' behavior and susceptibility to establishing a pilocarpine-induced status epilepticus.
View Article and Find Full Text PDFMaternal choline supplementation protects against age-associated cholinergic and GABAergic basal forebrain neuron degeneration in the Ts65Dn mouse model of Down syndrome and Alzheimer's disease.
Neurobiol Dis
November 2023
Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, USA; NYU Neuroscience Institute, New York University Grossman School of Medicine, New York, NY, USA; Department of Psychiatry, New York University Grossman School of Medicine, New York, NY, USA; Department of Neuroscience & Physiology, New York University Grossman School of Medicine, New York, NY, USA. Electronic address:
Article Synopsis
- Down syndrome (DS) is caused by an extra chromosome 21 and is linked to intellectual disabilities and age-related neurodegeneration, including Alzheimer's disease characteristics.
- A study using the Ts65Dn mouse model found that maternal choline supplementation (MCS) significantly protects vulnerable brain cells called basal forebrain cholinergic neurons (BFCNs) from degeneration.
- MCS also improved the health of another type of neuron, parvalbumin neurons, and showed overall neuroprotective effects, suggesting it could be a beneficial early treatment for those with DS and potentially for aging individuals as well.
Basal forebrain cholinergic neurons are vulnerable in a mouse model of Down syndrome and their molecular fingerprint is rescued by maternal choline supplementation.
FASEB J
June 2023
Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York, USA.
Basal forebrain cholinergic neuron (BFCN) degeneration is a hallmark of Down syndrome (DS) and Alzheimer's disease (AD). Current therapeutics in these disorders have been unsuccessful in slowing disease progression, likely due to poorly understood complex pathological interactions and dysregulated pathways. The Ts65Dn trisomic mouse model recapitulates both cognitive and morphological deficits of DS and AD, including BFCN degeneration and has shown lifelong behavioral changes due to maternal choline supplementation (MCS).
View Article and Find Full Text PDFCompensatory remodeling of a septo-hippocampal GABAergic network in the triple transgenic Alzheimer's mouse model.
J Transl Med
April 2023
Department of Pharmacology, University of North Carolina, Chapel Hill, NC, 27599, USA.
Background: Alzheimer's disease (AD) is characterized by a progressive loss of memory that cannot be efficiently managed by currently available AD therapeutics. So far, most treatments for AD that have the potential to improve memory target neural circuits to protect their integrity. However, the vulnerable neural circuits and their dynamic remodeling during AD progression remain largely undefined.
View Article and Find Full Text PDFThe impact of selective and non-selective medial septum stimulation on hippocampal neuronal oscillations: A study based on modeling and experiments.
Neurobiol Dis
May 2023
Bio-Imaging Lab, University of Antwerp, Antwerp, Belgium; Institute of Computer Science, Foundation for Research and Technology Hellas, Heraklion, Crete, Greece. Electronic address:
Alzheimer's disease (AD) is a neurodegenerative disorder with a rising socioeconomic impact on societies. The hippocampus (HPC), which plays an important role in AD, is affected in the early stages. The medial septum (MS) in the forebrain provides major cholinergic input to the HPC and has been shown to play a significant role in generating oscillations in hippocampal neurons.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!