Burrows et al.

Burrows et al.

            While reading Burrows et al., it was interesting to see the gene-environment interactions when knocking out mGlu5 and introducing environmental enrichment. The authors postulate “EE has been shown to upregulate NMDAR subunits” and this is demonstrated by the fact that EE seems to ameliorate schizophrenia related symptoms when the mGlu5 gene, another glutamate receptor is knocked out. mGlu5 tends to regulate the toxicity of glutamate and too much glutamate could be the cause for many of these schizophrenia like symptoms.

            It is interesting to see though that when NMDA antagonists such as MK-801 are introduced, EE seems to actually worsen symptoms of schizophrenia. For example, in the photo-beam arena, following the light being turned on, the KO mice in the environmental enrichment condition actually exhibited more locomotive activity, characteristic of schizophrenia. Similarly, in the pre pulse inhibition test, KO mice in the experimental condition were not able to inhibit their startle response as mice in other conditions. Both of these tasks involved the administration of MK-801 indicating NMDA receptor function can be impaired by the manipulation.

            Overall, I think Burrows et al. do a good job using supporting evidence for their model of environmental enrichment ameliorating schizophrenia-related symptoms in mGlu5 knockout mice. They demonstrate that glutamate toxicity has potential for schizophrenia etiology, i.e. support for the glutamate hypothesis. However, there are many variables involved. Environmental enrichment upregulates NMDA receptor subunits to prevent toxicity but also the function of knocking out a glutamate receptor impairs NMDA function implying that the system somehow works in concert.