Would social isolation reduce frontal myelination? : Nature:Sep 2012


Childhood experiences were at one time considered the key to adult mental disorders.The focus later shifted to ‘here and now’, both in mainstream psychology as well in pharmacotherapy. Large epidemiological studies have now brought our attention back to childhood experiences, particularly those of traumatic childhood experiences.

This study reveals some of the mechanisms by which our neural architecture is shaped differently be prior experiences.It also reveals the mechanisms behind such changes.

Studies of children raised in institutions where neglect was rampant showed that deprivation correlates with alterations in white matter tracts in the medial prefrontal cortex (mPFC), which are not reversed by subsequent foster care placement (H. T. Chugan et al Local brain functional activity following early deprivation: A study of postinstitutionalized Romanian orphans. (2001)  Eluvathingal et al., Abnormal brain connectivity in children after early severe socioemotional deprivation: A diffusion tensor imaging study.2006) Animal studies also point that juvenile social experience and forebrain white matter development are linked.

It is unclear whether any effect of social experience on oligodendrocytes, that produces the myelin,  is important for the establishment of normal adult neuronal circuits and their function.

Makinodan et al  housed male mice in isolation, in standard housing conditions or in enriched environments from postnatal day 21  onwards. On day 50, isolated mice showed reduced social interaction and working memory, both of which involve the PFC, compared with control and environmentally enriched mice. In addition, myelin was thinner, oligodendrocyte morphology was less complex and expression of myelin genes was reduced on day 65 in the PFC of isolated mice. Isolation  from day 21-35 was enough to cause this. Re introducing the mice back to social environment did not improve this.

Team looked at the  signaling pathways important for oligodendrocyte maturation such as neuregulin-1–ErbB (NRG1-ErbB). Oligodendrocytes express the ErbB2 and ErbB3 receptors , and hypomyelination occurs in mice with reduced oligodendrocyte ErbB signaling or NRG1 expression. Loss of ErbB3 signaling in oligodendrocytes during the critical period for myelination mimics the effects of social isolation.

The  research show that the effects of social experience on mPFC myelination depend, at least in part, on the social experience–dependent regulation of NRG1-ErbB3 signaling. They  propose that lack of social interactions during the juvenile period leads to reduced type III NRG1 expression by mPFC neurons. This result in reduced oligodendrocyte ErbB3 signaling and thus incomplete oligodendrocyte maturation and myelination.

These findings indicate that the effects of childhood isolation and neglect on adult mental health might be caused, at least in part, by alterations in oligodendrocytes and myelin development. The signalling pathways  behind this and their genetic context  may help to understand disorders like  schizophrenia and mood disorders, which usually manifest after the juvenile period and have been linked to alterations in white matter and myelination.

summary of the article:

A critical period for social experiencedependent oligodendrocyte maturation and myelination.Makinodan M, Rosen KM, Ito S, Corfas G. Science. 2012 Sep 14;337(6100):1357-60.

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