Intranasal exposure of manganese induces neuroinflammation and disrupts dopamine metabolism in the striatum and hippocampus

Neurosci Lett. 2020 Nov 1:738:135344. doi: 10.1016/j.neulet.2020.135344. Epub 2020 Sep 1.

Abstract

Prolonged exposure to manganese (Mn) may lead to toxic effects on the central nervous system (CNS). The mechanisms underlying neuronal death from exposure to Mn are not well understood but undoubtedly involve inflammatory processes. The aim of this study was to explore the effects of long-lasting intranasal Mn exposure in rats focusing on inflammatory processes and catecholamine (dopamine, norepinephrine) levels in the striatum and hippocampus. It was found that intranasal administration by instillation of MnCl2 solution once a day for 90 days leads to impaired movement and gait. We also observed that Mn concentration increased in the hippocampus (by 30 %) and in the striatum (by 220 %), dopamine (24 %) and DOPAC (35 %) were reduced in the striatum, and dopamine (190 %) and DOPAC (220 %) levels increased with simultaneously norepinephrine reduction (30 %) in the hippocampus. Observation of cytokine mRNA revealed increased expression of both assayed cytokines (IL-1β and TNF-α) in the hippocampus. There was a 3-fold increase in the expression of IBA-1 mRNA, 2-fold increase in NFκB mRNA, and dramatic reduction in IkB mRNA in the striatum. Taken together, intranasal exposure to a high dose of MnCl2 induces neuroinflammation and neurotransmission disturbance, but the effects are specific for each studied brain region.

Keywords: Dopamine; Manganese; Manganism; Neuroinflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Dopamine / metabolism*
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Inflammation / metabolism*
  • Interleukin-1beta / metabolism
  • Male
  • Manganese / administration & dosage*
  • Motor Activity / drug effects
  • Norepinephrine / metabolism
  • Rats
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • Manganese
  • Dopamine
  • Norepinephrine