Back to Search
Start Over
Inhibition of Reactive Astrocytes with Fluorocitrate Ameliorates Learning and Memory Impairment Through Upregulating CRTC1 and Synaptophysin in Ischemic Stroke Rats
- Source :
- Cellular and Molecular Neurobiology. 39:1151-1163
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- Ischemic stroke often causes motor and cognitive deficits. Deregulated glia gap junction communication, which is reflected by increased protein levels of glial fibrillary acidic protein (GFAP) and connexin 43 (Cx43), has been observed in ischemic hippocampus and has been associated with cognitive impairment in animal stroke models. Here, we tested the hypothesis that reactive astrocytes-mediated loss of synaptophysin (SYP) and CREB-regulated transcription coactivator 1 (CRTC1) contribute to dysfunction in glia gap junction communication and memory impairment after ischemic stroke. Male Sprague-Dawley rats were subjected to a 90-min middle cerebral artery occlusion (MCAO) with 7-day reperfusion. Fluorocitrate (1 nmol), the reversible inhibitor of the astrocytic tricarboxylic acid cycle, was injected into the right lateral ventricle of MCAO rats once every 2 days starting immediately before reperfusion. The Morris water maze was used to assess memory in conjunction with western blotting and immunostaining to detect protein expression and distribution in the hippocampus. Our results showed that ischemic stroke caused significant memory impairment accompanied by increased protein levels of GFAP and Cx43 in hippocampal tissue. In addition, the levels of several key memory-related important proteins including SYP, CRTC1, myelin basic protein and high-mobility group-box-1 were significantly reduced in the hippocampal tissue. Of note, inhibition of reactive astrocytes with fluorocitrate was shown to significantly reverse the above noted changes induced by ischemic stroke. Taken together, our findings demonstrate that inhibiting reactive astrocytes with fluorocitrate immediately before reperfusion may protect against ischemic stroke-induced memory impairment through the upregulation of CRTC1 and SYP.
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
Synaptophysin
Hippocampus
Morris water navigation task
Motor Activity
Hippocampal formation
Brain Ischemia
Rats, Sprague-Dawley
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Internal medicine
Glial Fibrillary Acidic Protein
medicine
Animals
Learning
Memory impairment
Citrates
HMGB1 Protein
Stroke
Memory Disorders
biology
Glial fibrillary acidic protein
business.industry
Myelin Basic Protein
Cell Biology
General Medicine
medicine.disease
Up-Regulation
Myelin basic protein
030104 developmental biology
Endocrinology
Astrocytes
Connexin 43
biology.protein
business
030217 neurology & neurosurgery
Transcription Factors
Subjects
Details
- ISSN :
- 15736830 and 02724340
- Volume :
- 39
- Database :
- OpenAIRE
- Journal :
- Cellular and Molecular Neurobiology
- Accession number :
- edsair.doi.dedup.....c41a3fb5d94858b69daa99ebb6ad9c76