PMID- 34588956 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20211001 IS - 1662-5102 (Print) IS - 1662-5102 (Electronic) IS - 1662-5102 (Linking) VI - 15 DP - 2021 TI - EAAT2 Expression in the Hippocampus, Subiculum, Entorhinal Cortex and Superior Temporal Gyrus in Alzheimer's Disease. PG - 702824 LID - 10.3389/fncel.2021.702824 [doi] LID - 702824 AB - 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. CI - Copyright (c) 2021 Yeung, Palpagama, Wood, Turner, Waldvogel, Faull and Kwakowsky. FAU - Yeung, Jason H Y AU - Yeung JHY AD - Centre for Brain Research, Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. FAU - Palpagama, Thulani H AU - Palpagama TH AD - Centre for Brain Research, Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. FAU - Wood, Oliver W G AU - Wood OWG AD - Centre for Brain Research, Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. FAU - Turner, Clinton AU - Turner C AD - Department of Anatomical Pathology, LabPlus, Auckland City Hospital, Auckland, New Zealand. FAU - Waldvogel, Henry J AU - Waldvogel HJ AD - Centre for Brain Research, Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. FAU - Faull, Richard L M AU - Faull RLM AD - Centre for Brain Research, Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. FAU - Kwakowsky, Andrea AU - Kwakowsky A AD - Centre for Brain Research, Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. LA - eng PT - Journal Article DEP - 20210913 PL - Switzerland TA - Front Cell Neurosci JT - Frontiers in cellular neuroscience JID - 101477935 PMC - PMC8475191 OTO - NOTNLM OT - Alzheimer's disease OT - EAAT2 OT - entorhinal cortex OT - glutamate transporter OT - hippocampus OT - subiculum OT - superior temporal gyrus COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/10/01 06:00 MHDA- 2021/10/01 06:01 PMCR- 2021/01/01 CRDT- 2021/09/30 07:10 PHST- 2021/04/30 00:00 [received] PHST- 2021/08/23 00:00 [accepted] PHST- 2021/09/30 07:10 [entrez] PHST- 2021/10/01 06:00 [pubmed] PHST- 2021/10/01 06:01 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fncel.2021.702824 [doi] PST - epublish SO - Front Cell Neurosci. 2021 Sep 13;15:702824. doi: 10.3389/fncel.2021.702824. eCollection 2021.