Acute Restraint Stress Augments 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Neurotoxicity via Increased Toxin Uptake into the Brain in C57BL/6 Mice

Neurosci Bull. 2018 Oct;34(5):849-853. doi: 10.1007/s12264-018-0254-2. Epub 2018 Jul 9.

Abstract

As an environmental risk factor, psychological stress may trigger the onset or accelerate the progression of Parkinson's disease (PD). Here, we evaluated the effects of acute restraint stress on striatal dopaminergic terminals and the brain metabolism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which has been widely used for creating a mouse model of PD. Exposure to 2 h of restraint stress immediately after injection of a low dose of MPTP caused a severe loss of striatal dopaminergic terminals as indicated by decreases in the dopamine transporter protein and dopamine levels compared with MPTP administration alone. Both striatal 1-methyl-4-phenylpyridinium ion (MPP+) and MPTP concentrations were significantly increased by the application of restraint stress. Striatal monoamine oxidase-B, which catalyzes the oxidation of MPTP to MPP+, was not changed by the restraint stress. Our results indicate that the enhanced striatal dopaminergic terminal loss in the stressed mice is associated with an increase in the transport of neurotoxin into the brain.

Keywords: Degeneration; Dopamine; Dopamine transporter; Dopaminergic neuron; MPP+; MPTP; Mouse model; Restraint stress.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / metabolism*
  • 1-Methyl-4-phenylpyridinium / metabolism*
  • Animals
  • Corpus Striatum* / drug effects
  • Corpus Striatum* / metabolism
  • Disease Models, Animal
  • Dopaminergic Neurons / drug effects*
  • MPTP Poisoning* / chemically induced
  • MPTP Poisoning* / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurotoxins / metabolism*
  • Restraint, Physical*
  • Stress, Psychological / metabolism*

Substances

  • Neurotoxins
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • 1-Methyl-4-phenylpyridinium