Mirtazapine has a therapeutic potency in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of Parkinson’s disease

Abstract

BackgroundMirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), shows multiple pharmacological actions such as inhibiting presynaptic α2 noradrenaline receptor (NAR) and selectively activating 5-hydroxytriptamine (5-HT) 1A receptor (5-HT1AR). Mirtazapine was also reported to increase dopamine release in the cortical neurons with 5-HT dependent manner. To examine whether mirtazapine has a therapeutic potency in Parkinson’s disease (PD), we examined this compound in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice model of PD.ResultsMale C57BL/6 mice were subjected to MPTP treatment to establish a PD model. Mirtazapine was administered once a day for 3 days after MPTP treatment. MPTP-induced motor dysfunction, assessed by beam-walking and rota-rod tests, was significantly improved by administration of mirtazapine. Biochemical examinations by high performance liquid chromatography and western blot analysis suggested mirtazapine facilitated utilization of dopamine by increasing turnover and protein expression of transporters, without affecting on neurodegenerative process by MPTP. These therapeutic effects of mirtazapine were reduced by administration of WAY100635, an inhibitor for 5HT1AR, or of clonidine, a selective agonist for α2-NAR, or of prazosin, an inhibitor for α1-NAR, respectively.ConclusionOur results showed mirtazapine had a therapeutic potency against PD in a mouse model. Because PD patients sometimes show depression together, it will be a useful drug for a future PD treatment.

Beyond muscles: The untapped potential of creatine

“…Systemic administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to mice [16,161–166] or non-human primates [167–169] is a well-accepted model of PD. Matthews et al [16] examined the neuroprotective effects of creatine in the mouse model of MPTP-induced PD.…”

Role of Immunity and Inflammation in the Pathophysiology of Neurodegenerative Diseases

“…One of the most widely used neurotoxin animal models is the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model, which mimics the biochemical changes that occur in PD [43,44]. MPTP specifically targets the neurons involved in PD, and causes apoptosis of dopaminergic cells in the substancia nigra.…”

Interdependent adrenergic receptor regulation of Arc and Zif268 mRNA in cerebral cortex

“…[37–40] and preclinical models suggest that they have cooperative roles in conferring therapeutic effects [20–22]. The α 2 -AR antagonist, mirtazipine, has anxiolytic and antidepressant effects in rodent models that require α 1 or β -AR signaling [21, 22].…”

“…The α 2 -AR antagonist, mirtazipine, has anxiolytic and antidepressant effects in rodent models that require α 1 or β -AR signaling [21, 22]. Similarly, mirtazapine improves motor dysfunction in a mouse model of Parkinson's disease that depends upon concurrent α 1 -AR stimulation [20]. In light of our findings, these therapeutic effects may rely on an α 2 -AR regulation of IEG expression that depends on α 1 or β-AR signaling,…”

“…In contrast to α 2 -AR, the role that α 1 and β-AR play in regulating basal Arc expression, however, has not been examined. Moreover, although ARs frequently work in coordinated manner to regulate plasticity [20–22], how α 1 , α 2 and β-AR integrate their signaling to modulate Arc and Zif268 has not been well studied.…”