A Hoshi1,2, A Tsunoda1, T Yamamoto1, M Tada3, A Kakita3, Y Ugawa1,4. 1. Department of Neurology, Fukushima Medical University, Fukushima, Japan. 2. IMS Shin Katsushika Royal Clinic, Tokyo, Japan. 3. Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan. 4. Fukushima Global Medical Science Center, Advanced Clinical Research Center, Fukushima Medical University, Fukushima, Japan.
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.
AIMS: Glutamateneurotoxicity 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 humanAD 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 humanAD 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: Shelley L Forrest; Jordan Hanxi Kim; Daniel R Crockford; Katharine Huynh; Rosie Cheong; Samantha Knott; Madison A Kane; Lars M Ittner; Glenda M Halliday; Jillian J Kril Journal: Neurochem Res Date: 2022-08-05 Impact factor: 4.414
Authors: Maria I Alvarez-Vergara; Alicia E Rosales-Nieves; Rosana March-Diaz; Guiomar Rodriguez-Perinan; Nieves Lara-Ureña; Clara Ortega-de San Luis; Manuel A Sanchez-Garcia; Miguel Martin-Bornez; Pedro Gómez-Gálvez; Pablo Vicente-Munuera; Beatriz Fernandez-Gomez; Miguel A Marchena; Andrea S Bullones-Bolanos; Jose C Davila; Rocio Gonzalez-Martinez; Jose L Trillo-Contreras; Ana C Sanchez-Hidalgo; Raquel Del Toro; Francisco G Scholl; Eloisa Herrera; Martin Trepel; Jakob Körbelin; Luis M Escudero; Javier Villadiego; Miriam Echevarria; Fernando de Castro; Antonia Gutierrez; Alberto Rabano; Javier Vitorica; Alberto Pascual Journal: Nat Commun Date: 2021-05-25 Impact factor: 14.919