engleski

Cholinergic and cognitive deficits in streptozotocin-induced rat model of sporadic Alzheimer’s disease

Introduction: Rats treated intracerebroventricularly with streptozotocin (STZ-icv) have been proposed as a model for sporadic Alzheimer’s disease (sAD).We aimed to characterize the STZ-icv dose- and post-treatment time-dependency of cognitive impairment and cholinergic deficit in the brain of the STZ-icv rat model. Material and methods: Male Wistar rats were given STZ (0.3, 1 and 3 mg/kg dose) or vehicle (controls) icvand sacrificed one, three, six or nine months afterwards. Cognitive functions were tested by Passive Avoidance Test.Acetylcholinesterase (AChE) activity was measured in hippocampus (HPC) and cortex (CTX) by Ellman’s method. Protein expression of muscarinic cholinergic receptor M1 in HPC and CTX was measured by Western blot analysis.Data were analysed by Kruskal-Wallis and Mann-Whitney U test (p<0.05). Results: STZ-icv rats exhibit significant cognitive decline, emphasized with higher doses (-45% to -90%). AChE activity in the STZ-icv (3 mg/kg) treated rats was significantly elevated in HPC after one (+20%) and nine (+32%) months.One and 3 mg STZ dose significantly altered the expression of muscarinic M1 receptors three months after the injection, found increased in CTX (+82, 89% and +67, 83%) and decreased in HPC (-18, 06% and 15, 01%). After 9 months, the expression of M1 receptor in CTX was decreased with all three STZ doses (-22, 5%/0.3 mg/kg, -20, 39%/1 mg/kg and -18, 34%/3 mg/kg). Conclusion: Results suggest long-term cognitive deficits which tend to correlate with observed cholinergic deficit at the highest STZ dose regimen, varying from the acute changes, followed by normalization and finally progressive decompensation effects. Acknowledgements: Supported by UKF and MZOS

sporadic Alzheimer’s disease; streptozotocin; cognitive deficit; cholinergic transmission

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