Abstract
Alzheimer’s disease (AD) is a neuropathological disorder characterized by the presence and accumulation of amyloid-beta plaques and neurofibrillary tangles. Glutamate dysregulation and the concept of glutamatergic excitotoxicity have been frequently described in the pathogenesis of a variety of neurodegenerative disorders and are postulated to play a major role in the progression of AD. In particular, alterations in homeostatic mechanisms, such as glutamate uptake, have been implicated in AD. An association with excitatory amino acid transporter 2 (EAAT2), the main glutamate uptake transporter, dysfunction has also been described. Several animal and few human studies examined EAAT2 expression in multiple brain regions in AD but studies of the hippocampus, the most severely affected brain region, are scarce. Therefore, this study aims to assess alterations in the expression of EAAT2 qualitatively and quantitatively through DAB immunohistochemistry (IHC) and immunofluorescence within the hippocampus, subiculum, entorhinal cortex, and superior temporal gyrus (STG) regions, between human AD and control cases. Although no significant EAAT2 density changes were observed between control and AD cases, there appeared to be increased transporter expression most likely localized to fine astrocytic branches in the neuropil as seen on both DAB IHC and immunofluorescence. Therefore, individual astrocytes are not outlined by EAAT2 staining and are not easily recognizable in the CA1–3 and dentate gyrus regions of AD cases, but the altered expression patterns observed between AD and control hippocampal cases could indicate alterations in glutamate recycling and potentially disturbed glutamatergic homeostasis. In conclusion, no significant EAAT2 density changes were found between control and AD cases, but the observed spatial differences in transporter expression and their functional significance will have to be further explored.
Highlights
Alzheimer’s disease (AD) is the most common cause of dementia worldwide and is linked with a decline in cognitive function, behavior, and memory (McKhann et al, 1984)
We examined the region- and layer-specific expression and pattern changes of excitatory amino acid transporter 2 (EAAT2) within the hippocampus, subiculum, entorhinal cortex, and superior temporal gyrus (STG) in AD post-mortem samples compared to control, to gain a better understanding of how the glutamatergic system is altered in the disease
In comparison to control sections, the CA2 region of AD sections exhibited much stronger immunoreactivity in astrocytic main branches surrounding some of the Neuronal Nuclei (NeuN) positive cell bodies within the str. pyramidale (Figure 2B, arrows), and this difference was observed within the CA3 (Figure 2C, arrows) and the str. granulosum of the dentate gyrus (DG) (Figure 2D)
Summary
Alzheimer’s disease (AD) is the most common cause of dementia worldwide and is linked with a decline in cognitive function, behavior, and memory (McKhann et al, 1984). In the central nervous system (CNS), glutamate serves three main functions: as an excitatory neurotransmitter, as the precursor molecule in the synthesis of γ-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the CNS (Erecinska and Silver, 1990), and as a fuel for mitochondrial metabolism (Dienel, 2013; McKenna et al, 2016). It plays a central role in the regular functioning of cognition, memory, and learning, as well as overall normal brain performance (Fonnum, 1984). Due to its tight regulation in normal physiology, the disruption of glutamate homeostasis as a mechanism for neuronal damage is one of the leading hypotheses implicating the glutamatergic system in AD pathogenesis
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
