Dexmedetomidine improves functional activity of dopaminergic neurons in MPTP-treated mice

Preservation of functions in dopaminergic neurons is a potential medication strategy for Parkinson's disease (PD) during perioperative periods. An increasing number of studies have shown that Dexmedetomidine (DEX) plays a neuroprotective role in patients with neurological conditions. However, how DEX exerts its effects on dopaminergic neurons in PD remains unclear. In this research, we report that DEX enhanced the firing activity of dopaminergic neurons via activation of alpha2 (α2) adrenoceptors and inhibition of potassium channel in vitro. Furthermore, DEX (50 μg/kg) exhibited its attenuation of motor deficits and neuroprotection of dopaminergic neurons via activation of α2 adrenoceptors in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced mice model. Importantly, DEX decreased protein kinase A (PKA) expression in MPTP-treated mice, and PKA agonist counteracted the beneficial effects of DEX on motor deficits. In addition, we further confirmed that the effect of DEX in decreasing motor deficits relies on the activation of dopaminergic neurons by using the reversal method with optogenetic inhibition of dopaminergic neurons. These results demonstrated that DEX improves the functional activity of dopaminergic neurons, providing a possible neurological basis for the impact of anesthetic agents on the progression of PD.