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Glycogen Synthase Kinase 3β; Inhibiton Improves Diabetes‐induced Cognitive Deficits in Type‐2 Diabetic Rats
Author(s) -
Datusalia Ashok Kumar,
Sharma Shyam Sunder
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.661.5
Subject(s) - endocrinology , neuroinflammation , medicine , hippocampus , morris water navigation task , type 2 diabetes , diabetes mellitus , neuroprotection , glutamate receptor , glycogen synthase , glucose homeostasis , streptozotocin , glycogen , insulin resistance , inflammation , receptor
Challenges to neural homeostasis in diabetes may produce different responses and damage in CNS and alteration in many measures of cognition in diabetes. This study was carried out to investigate the effect of GSk3β inhibitor (SB216763; SB) on diabetes‐induced cognitive deficit and its mechanism of neuroprotection in type 2 diabetic (T2D) rats. High fat diet with STZ was used to develop T2D in rats. Rats were tested for place navigation, fear & spatial memory using behavioral paradigms on 9, 12, 15 & 18 week after induction of T2D. Brain regions were tested for biochemical and neurotransmitter level. Treatment with SB was given from 15 week to 18 week at 3 doses 0.3, 0.6 & 1.2 mg/kg. T2D rats showed cognitive deficits after 15 week duration of diabetes and continue on 18th week compared to control. Further, elevated brain GABA level was observed after 15th week in T2D rats. Reduced glutamate level was also observed in T2D rats. Treatment with SB (0.6 mg/kg) for 3 weeks improved the diabetes‐induced cognitive deficits in passive avoidance, Y‐maze and MWM test. Improvement in memory also supported with decrease in GABA level and increased glutamate level. Administration of SB in diabetic rats also showed reduction in neuroinflammation in hippocampus and cortex. Improvement in cognitive deficits in diabetic rats by GSK3β inhibitor was attributed to reversal of neurotransmitters changes and reduction of neuroinflammation.