“It turns out that the Hoxb8 gene in question plays an important role in the development of immune cells known as microglia, which reside in the brain. Studies in which the researchers labeled Hoxb8 cells found that they show up in the brain exclusively in bone marrow-derived microglia. When they transplanted healthy bone marrow from control mice into the mutant animals, normal microglia made it to the animals' brains in about four weeks' time and many of the animals then stopped their incessant grooming, allowing their hair to grow back in, within three months of the procedure.”Microglia is a type of glial cell that acts as the first and main form of active immune defense in the central nervous system. During the process of blood cellular formation, some hematopoietic stem cells, which are any cells within the bone marrow whose function is to produce blood cells, give rise to microglia. According to Mario Capecchi of Howard Hughes Medical Institute and University of Utah School of Medicine, hox genes are heavily involved in hematopoietic stem cells, which are critical for the proper number and placement of embryonic segment structures, such as legs, antennae, and eyes.
Capecchi explains that “the classic job of microglia, which outnumber neurons in the brain, is to scan the brain for problems […] When they find that something is wrong -- maybe a pathogen has invaded or there has been a stroke -- they change their shape to infiltrate the area and "clean up the mess." Amazingly, microglia can scan the whole brain in only an hour.
These cells maneuver around the brain and make stops at active neuronal synapses monitoring brain activity. From this research, Capecchi believes that microglia may also regulate neural activity and when it is unable to, as in the case of Hoxb8 mutants, pathologies like OCD-like behaviors may result. The exact way in which microglia controls brain activity is not yet known; however these findings suggest that the immune system may have a larger role in mental health disorders. Capecchi states:
"we have provided strong support for the hypothesis that the excessive pathological grooming behavior exhibited by Hoxb8 mutant mice is caused by a defect in microglia. That a behavioral deficit could be corrected by bone marrow transplantation is indeed surprising. The therapeutic implications of our study on amelioration of neurological behavioral deficits in humans have not escaped us."Capecchi explains that a connection exists between the immune system and disorders such as depression, autism, Alzheimer's, OCD and schizophrenia, but it has never been entirely clear. This study should lead to more exciting discoveries in how microglia can affect neural activity and behavior. Perhaps our vast knowledge of the immune system could lead to more discoveries and treatments for mental illness.
Compulsive Behavior in Mice Cured by Bone Marrow Transplant
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