Clonidine ameliorates cognitive impairment induced by chronic cerebral hypoperfusion via up-regulation of the GABABR1 and GAD67 in hippocampal CA1 in rats

• Bilateral common carotid artery occlusion (2VO) induced cognitive deficit in rats.
• Clonidine could improve the cognitive deficits in rats induced by 2VO.
• 2VO decreased the level of GABABR1 and GAD67 in hippocampal CA1 in rats.
• Clonidine reversed the decrease in GABABR1 and GAD67 induced by 2VO in CA1 of rats.

Chronic cerebral hypoperfusion may cause cognitive impairment, but the underlying neurobiological mechanism is poorly understood. In this study, we investigated whether clonidine, an α2-adrenergic receptor agonist, could play neuroprotective role against chronic ischemic brain injury and the potential mechanism. Rats were subjected to permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO). Three weeks later, rats were administrated with 0.05 mg/kg clonidine (intraperitoneal injection, i.p.) for 7 days. Cognitive function was evaluated by Morris water maze (MWM). Immunofluorescence and western blots were used to detect the protein levels. Our results showed that the cognitive function was partially impaired, and the expression of neuronal nuclei (NeuN), glutamic acid decarboxylase 67 (GAD67) and γ-aminobutyric acid-B receptor 1 (GABABR1) in hippocampal CA1 area was attenuated after 2VO, which were not observed in CA3 and dentate gyrus (DG). Administration of 0.05 mg/kg clonidine (i.p.) for 7 days could improve cognitive function and the expression of NeuN, GAD67 and GABABR1 in CA1, but did not affect the protein levels in CA3 and DG. These findings demonstrated that clonidine could ameliorate cognitive deficits and neuronal impairment induced by chronic cerebral hypoperfusion via up-regulation of GABABR1 and GAD67 in hippocampal CA1.