Altered expression of glutamate transporter-1 and water channel protein aquaporin-4 in human temporal cortex with Alzheimer's disease.

Abstract

AIMS:

Glutamate neurotoxicity plays an important role in the pathogenesis of various neurodegenerative disorders. Many studies have demonstrated that glutamate transporter-1 (GLT-1), the dominant astrocytic glutamate transporter, is significantly reduced in the cerebral cortex of patients with Alzheimer's disease (AD), suggesting that glutamate-mediated excitotoxicity might contribute to the pathogenesis of AD. In a previous study, we have demonstrated marked alterations in the expression of the astrocytic water channel protein aquaporin-4 (AQP4) in relation to amyloid β deposition in human AD brains. As a functional complex, GLT-1 and AQP4 in astrocytes may play a neuroprotective role in the progression of AD pathology. However, few studies have examined the correlation between the expression of GLT-1 and that of AQP4 in human AD brain.

METHODS:

Here, using immunohistochemistry with antibodies against GLT-1 and AQP4, we studied the expression levels and distribution patterns of GLT-1 in areas showing various patterns of AQP4 expression in autopsied temporal lobes from eight patients with AD and five controls without neurological disorders.

RESULTS:

GLT-1 staining in the control group was present throughout the neocortex as uniform neuropil staining with co-localized AQP4. The AD group showed a significant reduction in GLT-1 expression, whereas cortical AQP4 immunoreactivity was more intense in the AD group than in the control group. There were two different patterns of GLT-1 and AQP4 expression in the AD group: (i) uneven GLT-1 expression in the neuropil where diffuse but intense AQP4 expression was evident, and (ii) senile plaque-like co-expression of GLT-1 and AQP4.

CONCLUSIONS:

These findings suggest disruption of glutamate/water homoeostasis in the AD brain.

• Authors: A Hoshi, A Tsunoda, T Yamamoto, M Tada, A Kakita, Y Ugawa
• Journal: Neuropathology and applied neurobiology (Neuropathol Appl Neurobiol) Vol. 44 Issue 6 Pg. 628-638 (10 2018) ISSN: 1365-2990 [Electronic] England
• PMID: 29405337 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 British Neuropathological Society.

Chemical References

• Aquaporin 4
• Excitatory Amino Acid Transporter 2

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (metabolism, pathology)
• Aquaporin 4 (metabolism)
• Excitatory Amino Acid Transporter 2 (metabolism)
• Female
• Humans
• Male
• Middle Aged
• Temporal Lobe (metabolism, pathology)