Adult-onset focal expression of mutated human tau in the hippocampus impairs spatial working memory of rats.

Behavioural Brain Research
Martina L MustrophJulio J Ramirez

Abstract

Tauopathy in the hippocampus is one of the earliest cardinal features of Alzheimer's disease (AD), a condition characterized by progressive memory impairments. In fact, density of tau neurofibrillary tangles (NFTs) in the hippocampus strongly correlates with severity of cognitive impairments in AD. In the present study, we employed a somatic cell gene transfer technique to create a rodent model of tauopathy by injecting a recombinant adeno-associated viral vector with a mutated human tau gene (P301L) into the hippocampus of adult rats. The P301L mutation is causal for frontotemporal dementia with parkinsonism-17 (FTDP-17), but it has been used for studying memory effects characteristic of AD in transgenic mice. To ascertain if P301L-induced mnemonic deficits are persistent, animals were tested for 6 months. It was hypothesized that adult-onset, spatially restricted tau expression in the hippocampus would produce progressive spatial working memory deficits on a learned alternation task. Rats injected with the tau vector exhibited persistent impairments on the hippocampal-dependent task beginning at about 6 weeks post-transduction compared to rats injected with a green fluorescent protein vector. Histological analysis of brains f...Continue Reading

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Citations

Apr 24, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Raphaëlle CaillierezMorvane Colin
Aug 16, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Alexander H StephanBen A Barres
Feb 24, 2015·Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology·Ronghao YuRuiwang Huang
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Sep 28, 2017·Reviews in the Neurosciences·Ahmed A MoustafaMichael Hornberger
Jun 22, 2017·Scientific Reports·Xinghua LiuXiaochuan Wang
Nov 11, 2019·Acta Neuropathologica Communications·Alexander J MoszczynskiKathryn Volkening
Jun 28, 2019·Frontiers in Neuroanatomy·Marco LuppiMatteo Cerri
Dec 18, 2020·Frontiers in Neurology·Michael J StrongKathryn Volkening

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