Alterations in dendritic GABAB receptor expression in an Alzheimer's disease mouse model

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 GABAB receptors (Niere, 2016). Metabotropic, GABAB 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 GABAB1 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 GABAB1 subunit expression in AD mice as compared to wildtypes (p<0.01). CONCLUSIONS: The data indicates increases in GABAB1 receptor subunits in AD while highlighting a potential avenue in which transsynaptic signaling is disrupted in early stages of AD.