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
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.
KeywordsCerebellum c-Fos Cytochrome c oxidase Early life stress Maternal separation
control female group
control male group
cytochrome c oxidase
dentate nucleus of the cerebellum
fastigial nucleus of the cerebellum
interposed nucleus of the cerebellum
lateral nucleus of the cerebellum
medial nucleus of the cerebellum
maternal separation 21 male group
maternal separation 21 female group
Morris water maze
This research was supported by Projects Grants of the MINECO (Ministerio de Economía y Competitividad del Gobierno de España) PSI2017-90806-REDT, PSI2017-83893-R, PSI 2015-73111-EXP, AINDACE Foundation, and BES-2014- 070562 to M.B. The funding source had no role in the design of the study, data collection, analysis, interpretation, and writing of the present manuscript.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
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