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Alterations in dendritic GABA B receptor expression in an Alzheimer’s disease mouse model
Author(s) -
McArdle Colin J,
Niere Farr,
Uneri Ayse,
RaabGraham Kimberly F
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.058557
Subject(s) - gabab receptor , neuroscience , biology , synaptic plasticity , metabotropic receptor , long term potentiation , microbiology and biotechnology , receptor , glutamate receptor , gabaa receptor , biochemistry
Background Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by memory deficits and cognitive decline. Major hallmarks that occur during early stages of disease progression include amyloid beta plaque, neurofibrillary tangles, and synaptic loss. The mechanisms that particularly govern synaptic loss, however, remain under investigation. Local, dendritic mRNA translation is critical in maintaining proper synaptic architecture as well as engagement with presynaptic terminals. A master regulator of this process is controlled by mammalian target of rapamycin complex 1 (mTORC1), whose activity has shown to be significantly increased in AD patients as well as respective animal models. Increases in mTORC1 activity have consequently shown to upregulate the translation of various downstream synaptic proteins, one of those being GABA B receptors (Niere, 2016). Metabotropic, GABA B receptors are critical in maintaining slow, sustained inhibition throughout the central nervous system. However, their significance towards synaptic function is understudied in the context of AD. Methods Our study utilized immunocytochemistry and microscopy to determine changes in GABA B1 receptor subunit expression in hippocampal dissociated neurons. Additionally, APP/PS1 transgenic mice were used as our model for AD. Results Immunocytochemical results indicate approximately a 22% increase in dendritic GABA B1 subunit expression in AD mice as compared to wildtypes (p<0.01). Conclusions The data indicates increases in GABA B1 receptor subunits in AD while highlighting a potential avenue in which transsynaptic signaling is disrupted in early stages of AD.