Effects of diabetes mellitus on astrocyte GFAP and glutamate transporters in the CNS

Glia. 2004 Nov 1;48(2):166-78. doi: 10.1002/glia.20068.


Diabetes mellitus increases the risk of central nervous system (CNS) disorders such as stroke, seizures, dementia, and cognitive impairment. The cellular mechanisms responsible for the increased risk of these disorders are incompletely understood. Astrocytes are proving critical for normal CNS function, and alterations in their activity could contribute to diabetes-related disturbances in the brain. We examined the effects of streptozotocin (STZ)-induced diabetes in rats on the level of the astrocyte intermediate filament protein, glial fibrillary acidic protein (GFAP), number of astrocytes, and levels of the astrocyte glutamate transporters, glutamate transporter-1 (GLT-1) and glutamate/aspartate transporter (GLAST), in the cerebral cortex, hippocampus, and cerebellum by Western blotting (WB) and immunohistochemistry (IH). Studies were carried out at 4 and 8 weeks of diabetes duration. Diabetes resulted in a significant decrease in GFAP protein levels (WB) in the hippocampus and cerebellum at 4 weeks and in the cerebral cortex, hippocampus and cerebellum by 8 weeks. Attenuated GFAP immunoreactivity (IH) was evident in the hippocampus, cerebellum and white matter regions such as the corpus callosum and external capsule at both 4 and 8 weeks of diabetes. Astrocyte cell counts of adjacent sections immunoreactive for S-100B were not different between control and diabetic animals. No significant differences were noted in astrocyte glutamate transporter levels in the cerebral cortex, hippocampus, or cerebellum at either time period (WB, IH). With the expanding list of astrocyte functions in the CNS, the role of astrocytes in diabetes-induced CNS disorders clearly warrants further investigation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Transport System X-AG / metabolism
  • Animals
  • Astrocytes / metabolism*
  • Brain / metabolism*
  • Brain / pathology
  • Brain / physiopathology
  • Brain Diseases / etiology
  • Brain Diseases / metabolism*
  • Brain Diseases / physiopathology
  • Cell Count
  • Cerebellum / metabolism
  • Cerebellum / pathology
  • Cerebellum / physiopathology
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Cerebral Cortex / physiopathology
  • Diabetes Complications / metabolism*
  • Diabetes Complications / pathology
  • Diabetes Complications / physiopathology
  • Diabetes Mellitus, Experimental / complications
  • Disease Models, Animal
  • Down-Regulation / physiology
  • Excitatory Amino Acid Transporter 2 / metabolism*
  • Glial Fibrillary Acidic Protein / metabolism*
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Hippocampus / physiopathology
  • Immunohistochemistry
  • Intermediate Filament Proteins / metabolism
  • Male
  • Rats
  • Rats, Wistar


  • Amino Acid Transport System X-AG
  • Excitatory Amino Acid Transporter 2
  • Glial Fibrillary Acidic Protein
  • Intermediate Filament Proteins