Alterations of GABA B Receptors in the APP/PS1 Mouse Model of Alzheimer's Disease

Document Type

Article

Publication Date

10-23-2020

Publication Title

Neurobiology of Aging

Volume

97

First page number:

129

Last page number:

143

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive decline of memory and cognitive function. The disease is characterized by the presence of amyloid plaques, tau tangles, altered inflammatory signaling, and alterations in numerous neurotransmitter signaling systems, including γ-aminobutyric acid (GABA). Given the extensive role of GABA in regulating neuronal activity, a careful investigation of GABA-related changes is needed. Further, given persistent inflammation has been demonstrated to drive AD pathology, the presence of GABA B receptor expressed on glia that serve a role regulation of the immune response adds to potential implications of altered GABA in AD. There has not previously been a systematic evaluation of GABA-related changes in an amyloid model of AD that specifically focuses on examining changes in GABA B receptors. In the present study, we examined alterations in several GABA-specific targets in the APP/PS1 mouse model at different ages. In the 4-month-old cohort, no significant deficits in spatial learning and memory or alterations in any of the GABAergic targets were observed compared with wild-type controls. However, we identified significant alterations in several GABA-related targets in the 6-month-old cohort that exhibited spatial learning deficits that include changes in glutamic acid decarboxylase 65, GABA transporter type 3, and GABA B receptors protein and mRNA levels. This was the same cohort at which learning and memory deficits and significant amyloid pathology was observed. Overall, our study provides evidence of altered GABAergic signaling in an amyloid model of AD at a time point consistent with AD-related deficits.

Keywords

APP/PS1; GABA; GABA B receptors; Microglia; Alzheimer's disease; Amyloid-beta

Disciplines

Gerontology | Neuroscience and Neurobiology

Language

English

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