Pramipexole ameliorates cognitive deficits in aged mice after sevoflurane anesthesia by upregulating dopamine D2 receptors in parvalbumin interneuron of the hippocampus.
Pramipexole ameliorates cognitive deficits in aged mice after sevoflurane anesthesia by upregulating dopamine D2 receptors in parvalbumin interneuron of the hippocampus.
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Original abstract
Pramipexole (PPX), dopamine D2/D3 receptor agonist, exhibits neuroprotective effects in patients with restless legs syndrome and Parkinson's disease. The present study aimed to investigate the cellular and molecular mechanisms underlying PPX treatment in memory and cognitive impairments induced by sevoflurane anesthesia in the aged mice. Aged mice received 2-h daily exposures to 60% oxygen, either with or without 3% sevoflurane, for three consecutive days. For interventional evaluation, PPX was administered intraperitoneally 1 h before sevoflurane exposure on three consecutive days. After the behavioral tests, hippocampal tissues were harvested from the mice for histochemical and biochemical examinations. Ex vivo electrophysiology was used to assess the activity of pyramidal neurons, while in vivo electrophysiology to evaluate changes in neural oscillations in the hippocampus of mice. PPX attenuated glial cell activation, reversed the downregulation of parvalbumin (PV) expression, rescued the reduction in the activity of PV interneuron and the imbalance of local neuronal excitatory/inhibitory, reversed the reduction in gamma oscillations, and ameliorated the downregulation of dopamine D2 receptors in the hippocampus after repeated sevoflurane exposure in aged mice. Our findings suggest that PPX confers neuroprotection, at least in part, by attenuating neuroinflammation and PV interneuron dysfunction via upregulation of hippocampal dopamine D2 receptors, thereby ameliorating memory and cognitive deficits.