Dataset Information

Glutamatergic receptor expression changes in the Alzheimer's disease hippocampus and entorhinal cortex.

ABSTRACT: Alzheimer's Disease (AD) is the leading form of dementia worldwide. Currently, the pathological mechanisms underlying AD are not well understood. Although the glutamatergic system is extensively implicated in its pathophysiology, there is a gap in knowledge regarding the expression of glutamate receptors in the AD brain. This study aimed to characterize the expression of specific glutamate receptor subunits in post-mortem human brain tissue using immunohistochemistry and confocal microscopy. Free-floating immunohistochemistry and confocal laser scanning microscopy were used to quantify the density of glutamate receptor subunits GluA2, GluN1, and GluN2A in specific cell layers of the hippocampal sub-regions, subiculum, entorhinal cortex, and superior temporal gyrus. Quantification of GluA2 expression in human post-mortem hippocampus revealed a significant increase in the stratum (str.) moleculare of the dentate gyrus (DG) in AD compared with control. Increased GluN1 receptor expression was found in the str. moleculare and hilus of the DG, str. oriens of the CA2 and CA3, str. pyramidale of the CA2, and str. radiatum of the CA1, CA2, and CA3 subregions and the entorhinal cortex. GluN2A expression was significantly increased in AD compared with control in the str. oriens, str. pyramidale, and str. radiatum of the CA1 subregion. These findings indicate that the expression of glutamatergic receptor subunits shows brain region-specific changes in AD, suggesting possible pathological receptor functioning. These results provide evidence of specific glutamatergic receptor subunit changes in the AD hippocampus and entorhinal cortex, indicating the requirement for further research to elucidate the pathophysiological mechanisms it entails, and further highlight the potential of glutamatergic receptor subunits as therapeutic targets.

SUBMITTER: Yeung JHY

PROVIDER: S-EPMC8549033 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Glutamate is the main excitatory neurotransmitter in the central nervous system, responsible for a plethora of cellular processes including memory formation and higher cerebral function and has been implicated in various neurological disease states. Alzheimer's disease (AD) is the leading neurodegenerative disorder worldwide and is characterized by significant cell loss and glutamatergic dysfunction. While there has been a focus on ionotropic glutamatergic receptors few studies have attempted to elucidate the pathological changes of metabotropic glutamate receptors (mGluRs) in AD. mGluRs are G-protein coupled receptors which have a wide-ranging functionality, including the regulation of neuronal injury and survival. In particular, the group I mGluRs (mGluR1 and mGluR5) are associated with ionotropic receptor activation and upregulation with resultant glutamate release in normal neuronal functioning. The mGluR subtype 1 splice variant a (mGluR1α) is the longest variant of the mGluR1 receptor, is localized to dendritic processes and is mainly plasma membrane-bound. Activation of mGluR1a has been shown to result in increased constitutive activity of ionotropic receptors, although its role in neurodegenerative and other neurological diseases is controversial, with some animal studies demonstrating potential neuroprotective properties in excito- and neurotoxic environments. In this study, the expression of mGluR1a within normal and AD human hippocampal tissue was quantified using immunohistochemistry. We found a significantly reduced expression of mGluR1α within the stratum pyramidale and radiatum of the CA1subregion, subiculum, and entorhinal cortex. This downregulation could result in potential dysregulation of the glutamatergic system with consequences on AD progression by promoting excitotoxicity, but alternatively may also be a neuroprotective mechanism to prevent mGluR1α associated excitotoxic effects. In summary, more research is required to understand the role and possible consequences of mGluR1α downregulation in the human AD hippocampus, subiculum and entorhinal cortex and its potential as a therapeutic target.

Dataset Information

Glutamatergic receptor expression changes in the Alzheimer's disease hippocampus and entorhinal cortex.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets