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.

Females exhibit higher GluA2 levels and outperform males in active place avoidance despite increased amyloid plaques in TgF344-Alzheimer’s rats

“…Mitigation of memory deficits resulted in increased GluA1 and GluA2 levels in the 3xTg-AD mouse model, suggesting that AMPA receptors play a critical role in synaptic plasticity and memory 67 . Nevertheless, GluA2 is significantly expressed in the human post-mortem hippocampus of AD patients relative to controls, specifically in the stratum moleculare of the DG 68 .…”

Females outperform males in spatial learning despite increased amyloid plaques and microgliosis in a TgF344-AD rat model of Alzheimer’s disease

“…Also, mitigation of memory deficits resulted in increased GluA1 and GluA2 levels in the 3xTg-AD mouse model, suggesting that AMPA receptors play a critical role in maintaining synaptic plasticity and memory [41]. While these finding support a critical role for GluA2 in synaptic plasticity, GluA2 is significantly expressed in the human post-mortem hippocampus of AD patients relative to controls, specifically in the stratum moleculare of the DG [54].…”

Roles of traditional chinese medicine regulating neuroendocrinology on AD treatment

“…Accumulation of toxic substances in AD will damage receptor function, resulting in calcium imbalance and excitability toxicity. In the end, these will cause autophagy and apoptosis of neurons ( 103 ). Tenuifolin (TEN), the main component of Polygala tenuifolia, has neuroprotective performance.…”