OPINION: This week Nature published a very interesting and possibly groundbreaking study on schizophrenia. It doesn’t mention MECP2 but it does talk about the role of the pruning process in the brain. The way our brains develop is by creating a bunch of new connections and then trimming away the ones that are not needed or helpful. The article suggests that schizophrenia develops when the pruning process goes too far in some parts of the brain. This is also consistent in some earlier reports that did suggest that certain defects in MECP2 were implicated in early onset schizophrenia.
Too much or too little MeCP2 activity has also been connected to a number of other conditions, such as Sjogren syndrome, Lupus, some cases of Angelman syndrome, some cases of intellectual disability and autism not consistent with Rett or MECP2 duplication syndrome, Hirschsprung syndrome, and others. High or low levels of MeCP2 also appear to promote or inhibit the growth of tumors in prostate and colon cancer.
As learning about Rett syndrome and MECP2 duplication syndrome may be critical for learning about the normal function of the MeCP2 protein and MECP2 gene, hopefully as well as for successfully treating these syndromes, the role of MECP2 in all of these other conditions may prove critical to our understanding. In addition, the growing list of MECP2-realted disorders provides an additional rationale for research on Rett and MECP2 duplication because learning to regulate MeCP2 successfully may result in benefits to a much larger group of individuals than the relatively small numbers affected directly by Rett or duplication syndrome.
Getting back to the schizophrenia study and pruning. Some attention has already been given to the role of MeCP2 in regulating something called 5hmc and HLA (Human Leukocyte Antigen). This may suggest at least part of the reason that MeCP2 influences both the connection of neurons and the immune system. It may also suggest what might be going on in the regression that affects individuals with Rett syndrome and MECP2 Duplication Syndrome.
During the first couple of years of life more and more connections are being made in the brain. Around that time serious pruning starts to preferentially keep some pathways and eliminate less essential ones. Low MeCP2 activity may lead to this pruning process going way too far and pruning away important pathways that are needing to maintain skills and build new ones in Rett syndrome. In MECP2 duplication syndrome, too much MeCP2 activity may inhibit pruning and so that more and more connections are made overwhelming the system and eventually resulting in regression when the the brain is no longer able to selective activate the relevant connections. Of course, these scenarios are pure speculation, but insight into what is really happening may be greatly aided by trying to look at the big picture and learning from all the MECP2 related research.
Of course, good research requires focus, and researchers must maintain their primary focus on their own areas, but looking outward once in awhile at the the big picture may prove very useful.