Alzheimer's Disease-associated Region-specific Decrease of Vesicular Glutamate Transporter Immunoreactivity in the Medial Temporal Lobe and Superior Temporal Gyrus

被引:1
作者
Wood, Oliver W. G. [1 ,2 ]
Walby, Josh [1 ,2 ]
Yeung, Jason H. [1 ,2 ]
Ke, Stephen [1 ,2 ]
Palpagama, Thulani H. [1 ,2 ]
Turner, Clinton [3 ]
Waldvogel, Henry J. [1 ,2 ]
Faull, Richard L. M. [1 ,2 ]
Kwakowsky, Andrea [1 ,2 ,4 ,5 ]
机构
[1] Univ Auckland, Ctr Brain Res, Auckland, New Zealand
[2] Univ Auckland, Fac Med & Hlth Sci, Dept Anat & Med Imaging, Auckland, New Zealand
[3] Auckland City Hosp, Dept Anat Pathol, LabPlus, Auckland, New Zealand
[4] Univ Galway, Galway Neurosci Ctr, Sch Med, Pharmacol & Therapeut, Galway, Ireland
[5] Ollscoilna Gaillimhe Univ Galway, Galway Neurosci Ctr, Sch Med, Pharmacol & Therapeut, Galway H91 W5P7, Ireland
关键词
Alzheimer's disease; vesicular glutamate transporters; VGLUT1; VGLUT2; human brain; PYRAMIDAL NEURONS; TERMINALS VGLUT1; DOWN-REGULATION; HUMAN BRAIN; ADULT; NEUROTRANSMITTER; EXPRESSION; SUBICULUM; RELEASE; TARGET;
D O I
10.1016/j.neuroscience.2024.03.027
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
disease (AD) is a progressive neurodegenerative disorder for which there are very limited treatment options. Dysfunction of the excitatory neurotransmitter system is thought to play a major role in the pathogenesis of this condition. Vesicular glutamate transporters (VGLUTs) are key to controlling the quantal release of glutamate. Thus, expressional changes in disease can have implications for aberrant neuronal activity, raising the possibility of a therapeutic target. There is no information regarding the expression of VGLUTs in the human medial temporal lobe in AD, one of the earliest and most severely affected brain regions. This study aimed to quantify and compare the layer -specific expression of VGLUT1 and VGLUT2 between control and AD cases in the hippocampus, subiculum, entorhinal cortex, and superior temporal gyrus. Free-floating fluorescent immunohistochemistry was used to label VGLUT1 and VGLUT2 in the hippocampus, subiculum, entorhinal cortex, and superior temporal gyrus. Sections were imaged using laser -scanning confocal microscopy and transporter densitometric analysis was performed. VGLUT1 density was not significantly different in AD tissue, except lower staining density observed in the dentate gyrus stratum moleculare ( p = 0.0051). VGLUT2 expression was not altered in the hippocampus and entorhinal cortex of AD cases but was significantly lower in the subiculum ( p = 0.015) and superior temporal gyrus ( p = 0.0023). This study indicates a regionally specific vulnerability of VGLUT1 and VGLUT2 expression in the medial temporal lobe and superior temporal gyrus in AD. However, the causes and functional consequences of these disturbances need to be further explored to assess VGLUT1 and VGLUT2 as viable therapeutic targets. (c) 2024 The Author(s). Published by Elsevier Inc. on behalf of IBRO. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
引用
收藏
页码:75 / 87
页数:13
相关论文
共 52 条
[21]   Down-regulation of vesicular glutamate transporters precedes cell loss and pathology in Alzheimer's disease [J].
Kirvell, Sara L. ;
Esiri, Margaret ;
Francis, Paul T. .
JOURNAL OF NEUROCHEMISTRY, 2006, 98 (03) :939-950
[22]   Molecular characterization of selectively vulnerable neurons in Alzheimer's disease [J].
Leng, Kun ;
Li, Emmy ;
Eser, Rana ;
Piergies, Antonia ;
Sit, Rene ;
Tan, Michelle ;
Neff, Norma ;
Li, Song Hua ;
Rodriguez, Roberta Diehl ;
Suemoto, Claudia Kimie ;
Leite, Renata Elaine Paraizo ;
Ehrenberg, Alexander J. ;
Pasqualucci, Carlos A. ;
Seeley, William W. ;
Spina, Salvatore ;
Heinsen, Helmut ;
Grinberg, Lea T. ;
Kampmann, Martin .
NATURE NEUROSCIENCE, 2021, 24 (02) :276-287
[23]  
Liguz-Lecznar M, 2007, ACTA NEUROBIOL EXP, V67, P207, DOI 10.55782/ane-2007-1649
[24]  
Lopez JAS, 2019, HAND CLINIC, V167, P231, DOI 10.1016/B978-0-12-804766-8.00013-3
[25]  
Mai J.K., 2015, Atlas of the Human Brain, V4th
[26]   VGLUT1 functions as a glutamate/proton exchanger with chloride channel activity in hippocampal glutamatergic synapses [J].
Martineau, Magalie ;
Guzman, Raul E. ;
Fahlke, Christoph ;
Klingauf, Jurgen .
NATURE COMMUNICATIONS, 2017, 8
[27]   The subiculum: Unique hippocampal hub and more [J].
Matsumoto, Nobuyoshi ;
Kitanishi, Takuma ;
Mizuseki, Kenji .
NEUROSCIENCE RESEARCH, 2019, 143 :1-12
[28]   Vesicular Glutamate Transporter Changes in the Cortical Default Mode Network During the Clinical and Pathological Progression of Alzheimer's Disease [J].
Mi, Zhiping ;
Abrahamson, Eric E. ;
Ryu, Angela Y. ;
Malek-Ahmadi, Michael ;
Kofler, Julia K. ;
Fish, Kenneth N. ;
Sweet, Robert A. ;
Villemagne, Victor L. ;
Schneider, Julie A. ;
Mufson, Elliott J. ;
Ikonomovic, Milos D. .
JOURNAL OF ALZHEIMERS DISEASE, 2023, 94 (01) :227-246
[29]   Amyloid-β(1-42) peptide induces rapid NMDA receptor-dependent alterations at glutamatergic synapses in the entorhinal cortex [J].
Olajide, Olayemi Joseph ;
Chapman, Clifton Andrew .
NEUROBIOLOGY OF AGING, 2021, 105 :296-309
[30]   Glutamate transport and storage in synaptic vesicles [J].
Özkan, ED ;
Ueda, T .
JAPANESE JOURNAL OF PHARMACOLOGY, 1998, 77 (01) :1-10