Accelerated aging of the GABAergic septohippocampal pathway and decreased hippocampal rhythms in a mouse model of Alzheimer's disease
Open accessAbstract
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.—Rubio, S. E., Vega‐Flores, G., Martínez, A., Bosch, C., Pérez‐Mediavilla, A., del Río, J., Gruart, A., Delgado‐García, J. M., Soriano, E., Pascual, M. Accelerated aging of the GABAergic septohippocampal pathway and decreased hippocampal rhythms in a mouse model of Alzheimer's disease. FASEB J. 26, 4458–4467 (2012). www.fasebj.org
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Transgenic mice with AD-like pathology have reduced gamma power, and in one model this reduction precedes cognitive impairment and amyloid plaque formation.
“Transgenic mice with AD-like pathology were found to have reduced gamma power that, in one model, precedes cognitive impairment and amyloid plaque formation [21,22].”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [22]
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- Authors
- Rubio, S. E., Vega‐Flores, G., Martínez, A., Bosch, C., Pérez‐Mediavilla, A., Río, J. D., Gruart, A., Delgado‐García, J. M., Soriano, E., & Pascual, M.
- Affiliations
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Universidad Pablo de Olavide (ES)
- Developmental Neurobiology and Regeneration Laboratory Institute for Research in Biomedicine Barcelona Spain
- Centro de Investigación Biomédica en Red para Enfermedades Neurodegenerativas Madrid Spain
- Division of Neurosciences Pablo de Olavide University Seville Spain
- Corresponding author
- Pascual, Marta
- ORCID
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2012-07-26
- Volume
- 26
- Issue
- 11
- Pages
- 4458-4467
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2144901851
- Cited by
- 98
- References
- 60
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 6 · 2023: 7 · 2022: 5 · 2021: 9 · 2020: 13 · 2019: 6 · 2018: 6 · 2017: 6 · 2016: 11 · 2015: 3 · 2014: 5 · 2013: 8 · 2012: 1
- FWCI
- 3.65
- Type
- journal article
- Language
- en
- Open access
- green
- zenodo.org
- Licence
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
- Funders
- Institute for Research in Biomedicine
- Ministry of Science and Innovation, New Zealand (BFU2008‐3980)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- Alzheimer's disease, theta oscillations, gamma oscillations, normal aging, interneurons, cholinergic innervation, mouse model
- MeSH terms
- Aging, Alzheimer Disease, Animals, Disease Models, Animal, Hippocampus, Male, Mice, Inbred C57BL, Mice, Neurologic Mutants, Mice, Transgenic, Septal Nuclei, Theta Rhythm, Amyloid beta-Protein Precursor, Mice, GABAergic Neurons
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