The effects of preweaning manganese exposure on spatial learning ability and p-CaMKIIα level in the hippocampus

Neurotoxicology. 2016 Jan:52:98-103. doi: 10.1016/j.neuro.2015.11.013. Epub 2015 Nov 23.

Abstract

Background: The effects and mechanisms of preweaning Manganese (Mn) exposure on cognitive dysfunction remain unclear.

Objective: This study evaluated the effects of preweaning Mn exposure on spatial learning and memory as well as the protein expression of CaMKIIα and p-CaMKIIα.

Methods: We treated neonate rats with Mn(2+) doses of 0 (control group), 10, 20 and 30mg of Mn(2+) per kg body weight (Mn-exposed groups) over postnatal day (PND) 1-21 by intraperitoneal injection. The ability of spatial learning and memory was tested on PND 22 using the Morris water maze (MWM), while the protein expressions of CaMKIIα and p-CaMKIIα in the hippocampus were evaluated by Western blotting. The levels of Mn in the blood and hippocampus were measured by inductively coupled plasma-mass spectrometry (ICP-MS).

Results: The rats in Mn-exposed groups showed a significant delay in spatial learning ability on the third day of the MWM without dose-dependent differences, but there was no effect on the spatial memory ability. p-CaMKIIα, but not CaMKIIα protein expression significantly reduced in the Mn-exposed group.

Conclusion: These findings suggested that the inhibition of p-CaMKIIα could be one of the mechanisms involved in the occurrence of Mn-induced cognitive impairments.

Keywords: Hippocampus; Manganese; Neonate rats; P-CaMKIIα; Spatial learning and memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / biosynthesis
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
  • Dose-Response Relationship, Drug
  • Female
  • Hippocampus / drug effects*
  • Hippocampus / metabolism*
  • Locomotion / drug effects
  • Male
  • Manganese / blood
  • Manganese / metabolism
  • Manganese / toxicity*
  • Maze Learning / drug effects
  • Phosphorylation / drug effects
  • Rats
  • Spatial Learning / drug effects*
  • Spatial Learning / physiology

Substances

  • Manganese
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2