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

  • Alba Gutiérrez-Menéndez
  • María BanqueriEmail author
  • Marta Méndez
  • Jorge L. Arias
Original Paper


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.


Cerebellum 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


maternal separation 21 male group


maternal separation 21 female group


Morris water maze


postnatal day


Funding Information

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.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Psychology, Laboratory of NeuroscienceUniversity of OviedoOviedoSpain
  2. 2.Instituto de Neurociencias del Principado de Asturias (INEUROPA)OviedoSpain

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