Methylene blue protects dopaminergic neurons against MPTP‐induced neurotoxicity by upregulating brain‐derived neurotrophic factor

Abstract

The relatively old, yet clinically used, drug methylene blue (MB) is known to possess neuroprotective properties by reducing aggregated proteins, augmenting the antioxidant response, and enhancing mitochondrial function and survival in various models of neurodegenerative diseases. In this study, we aimed to examine the effects of MB in Parkinson's disease (PD) in vivo and in vitro models by using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/1-methyl-4-phenylpyridinium (MPP ) with a focus on possible effects on induction of neurotrophic factors. Our results indicate that pretreatment with MB significantly attenuated MPTP-induced loss of dopaminergic neurons, glial cell activation, and depletion of dopamine. We also found that MB upregulated brain-derived neurotrophic factor (BDNF) and activated its downstream signaling pathways, suggesting that BDNF might be a contributor to MB-associated neuroprotection. Specific inhibition of the BDNF receptor or extracellular signal-regulated kinase (Erk) reversed the MB-mediated protection against MPP toxicity, thus implying a role for BDNF and the Erk pathway in the neuroprotective effects. Taken together, our data suggest that MB protects neurons from MPTP neurotoxicity via induction of BDNF. Further study to determine whether MB preserves dopaminergic neurons in the brains of PD patients is warranted.

Concentration-Dependent Activity of Hydromethylthionine on Cognitive Decline and Brain Atrophy in Mild to Moderate Alzheimer’s Disease

“…Since these LMTM effects are not seen in wild-type mice, they are likely to represent secondary consequences of the primary action of LMTM on tau oligomers in synaptic terminals and in mitochondria. The MT moiety (given as MTC) has been reported to affect dopaminergic function in mouse models of Parkinson's disease [43][44][45]. We have found that LMTM increases hippocampal acetylcholine levels in both tau transgenic and wild-type mice, and that this effect is also eliminated by pretreatment with a cholinesterase inhibitor [32].…”

Concentration-Dependent Activity of Hydromethylthionine on Clinical Decline and Brain Atrophy in a Randomized Controlled Trial in Behavioral Variant Frontotemporal Dementia

“…In addition to effects on pathological protein aggregation, the MT moiety has been reported to have effects on dopamine and serotonin. Bhurtel and colleagues reported that MTC (given in the oxidized MT + form as MTC at a dose of 20 mg/kg intraperitoneally) restores dopamine levels in a mouse model of Parkinson's disease using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) [70]. MPTP is not itself toxic, but produces toxicity in dopaminergic neurons via a metabolite produced by monoamine oxidase in the brain [71].…”

Mitochondria as a target for neuroprotection: role of methylene blue and photobiomodulation

“…(1-methyl-4-phenyl-1, 2, 3, 6tetrahydropyridine)-induced PD animal model to evaluate the effect of MB on dopamine cells found that MB could cause the upregulation of brainderived neurotrophic factor (BDNF) and induce the activation of its downstream signaling pathways, indicating BDNF may be one of the contributing factors for MB-mediated neuroprotection [286].…”