How Does Maternal Separation Affect the Cerebellum? Assessment of the Oxidative Metabolic Activity and Expression of the c-Fos Protein in Male and Female Rats

Cerebellum. 2020 Feb;19(1):68-77. doi: 10.1007/s12311-019-01087-5.

Abstract

Early life stress increases the risk of abnormal brain development, and it is associated with psychological disorders. Maternal separation is an established animal model of early life stress that produces changes in the development of the central nervous system. The objective of this study was to evaluate the effect of maternal separation on the rat cerebellum, both behaviourally and physiologically. We used 32 rats, males (n = 8) and females (n = 7), subjected to maternal separation for 21 days and a control group (9 males and 8 females). Spatial reference memory was assessed using the Morris water maze, and brain metabolic activity and the expression of an immediate early gene were determined, respectively, using the histochemical technique of cytochrome c oxidase and the immunocytochemistry of c-Fos. Results showed that both groups successfully performed the spatial memory task. Although there were no behavioural differences, the experimental group showed lower metabolic activity in the medial nucleus of the cerebellum, as well as fewer c-Fos-positive cells in the three deep nuclei of the cerebellum. These decreases could contribute to the emotional or behavioural impairments reported in maternal separation subjects.

Keywords: Cerebellum; Cytochrome c oxidase; Early life stress; Maternal separation; c-Fos.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cerebellum / metabolism*
  • Female
  • Gene Expression Regulation, Developmental*
  • Male
  • Maternal Deprivation*
  • Maze Learning / physiology
  • Oxidative Stress / physiology*
  • Proto-Oncogene Proteins c-fos / biosynthesis*
  • Proto-Oncogene Proteins c-fos / genetics
  • Random Allocation
  • Rats
  • Rats, Wistar

Substances

  • Proto-Oncogene Proteins c-fos