Differences in Synaptic Dysfunction Between rTg4510 and APP/PS1 Mouse Models of Alzheimer’s Disease

Autor: Geoffrey Tombaugh, Simon Gelman, Afshin Ghavami, Jonathan D. Palma
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
medicine.medical_specialty
Biophysics
Hippocampus
Mice
Transgenic
tau Proteins
Hippocampal formation
Neurotransmission
Synaptic Transmission
Presenilin
03 medical and health sciences
Amyloid beta-Protein Precursor
Mice
0302 clinical medicine
Alzheimer Disease
Internal medicine
mental disorders
medicine
Amyloid precursor protein
Presenilin-1
Animals
Humans
Analysis of Variance
biology
synaptic dysfunction
General Neuroscience
tauopathy
Age Factors
Excitatory Postsynaptic Potentials
Long-term potentiation
General Medicine
Amyloidosis
electrophysiology
Electric Stimulation
Psychiatry and Mental health
Clinical Psychology
Disease Models
Animal
030104 developmental biology
Endocrinology
Synaptic plasticity
Mutation
Synapses
Excitatory postsynaptic potential
biology.protein
Geriatrics and Gerontology
030217 neurology & neurosurgery
Research Article
Zdroj: Journal of Alzheimer's Disease
ISSN: 1875-8908
1387-2877
Popis: Genetically modified mice have provided insights into the progression and pathology of Alzheimer's disease (AD). Here, we have examined two mouse models of AD: the rTg4510 mouse, which overexpresses mutant human Tau gene, and the APP/PS1 mouse, which overexpresses mutant human genes for amyloid precursor protein and presenilin 1. Both models exhibit deficits in hippocampal function, but comparative analyses of these deficits are sparse. We used extracellular field potential recordings in hippocampal slices to study basal synaptic transmission (BST), paired-pulse facilitation (PPF), and long-term potentiation (LTP) at the Schaffer collateral-CA1 pyramidal cell synapses in both models. We found that 6-7, but not 2-3-month-old rTg4510 mice exhibited reduced pre-synaptic activation (fiber volley (FV) amplitude, ∼50%) and field excitatory post-synaptic potential (fEPSP) slope (∼40%) compared to wild-type controls. In contrast to previous reports, BST, when controlled for FV amplitude, was not altered in rTg4510. APP/PS1 mice (2-3 mo and 8-10 mo) had unchanged FV amplitude compared to wild-type controls, while fEPSP slope was reduced by ∼34% in older mice, indicating a deficit in BST. PPF was unchanged in 8-10-month-old APP/PS1 mice, but was reduced in 6-7-month-old rTg4510 mice. LTP was reduced only in older rTg4510 and APP/PS1 mice. Our data suggest that BST deficits appear earlier in APP/PS1 than in rTg4510, which exhibited no BST deficits at the ages tested. However, FV and synaptic plasticity deficits developed earlier in rTg4510. These findings highlight fundamental differences in the progression of synaptic pathology in two genetically distinct models of AD.
Databáze: OpenAIRE
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