Week 6 Articles

Both the Burrows and Ayhan papers properly follow up the last week papers regarding animal modeling of schizophrenia.  The conversation continues with an in depth look at the temporal effects of DISC1 expression during developmental periods and the next step in establishing the role of environmental influence with a genetic predisposition to developing psychiatric disorder.  The Ayhan paper presented a sound argument, but I was preferential to reading about the potential of environmental influences that was discussed in the Burrows paper.

The Ayhan paper showed that increased expression of DISC1 functions in inducing a later onset of schizophrenic symptoms, but that this effect is dependent on when specifically expression is varied during development.  Over expression of hDISC1 was administered in prenatal, postnatal and pre+postnatal cohorts and the results of many interactions were presented succinctly in a table.  Prenatal development was discussed as the migratory stages of the interneurons while postnatal would be the finalizing stages of neural differentiation.  The most outstanding effect of prenatal administration was a decrease in total brain volume, while postnatal overexpression of DISC1 led to more behavioral changes.  Knowing that the onset of symptoms is predominantly post-adolescence it was fitting that the next paper I read was prepared to factor in the environmental influence on modulating symptoms.

The Burrows paper did a nice job bringing together genetically predisposed glutamatergic signaling dysfunction and the grounds for environmental influence on the development of illness.  The knockout of mGlu5 had clear implications in disrupting NMDAr inhibitory signaling and symptomatically presented as hyperactivity, a significant PPI deficit and increased latency to escape in the water maze.  Burrows used the knockout in conjunction with an enriched housing environment to demonstrate a method of resilience to the mentioned symptoms in modeling psychiatric disorder.  An environmental involvement in the onset of human schizophrenia has been very convincing.  The enriched environment consisted of larger exploratory spaces, a number of novel stimuli and a regiment for extra activity throughout the week.  Addition of the NMDAr antagonist MK-801 touched more specifically on the tight relationship between the two receptors, and provided further evidence for the potentiating effects of a modulated environment.