Brain Abnormality Linked to Psychiatric Disorders
New research on mice shows that the loss of a protein called MeCP2 in a specific group of inhibitory neurons in the brain produces almost all features associated with Rett syndrome.
Babies (mostly girls) born with Rett syndrome may seem normal at first, but mental and motor development slows down or stops between three months and three years of age. This may include loss of speech, learning difficulties and balance and walking problems. Some symptoms mimic those of autism.
Inhibitory (gamma-amino-butyric-acid [GABA]-ergic) neurons account for only 15 to 20 percent of the total number of neurons in the brain. However, losing MeCP2 reduces the number of enzymes required to produce the neurotransmitter GABA and in turn creates a 30 to 40 percent reduction in levels of this neurotransmitter, which greatly alters neuron communication.
Previous research has shown that expression of these enzymes is also lower in some patients with autism, schizophrenia and bipolar disorder, said Dr. Hsiao-Tuan Chao, an M.D./Ph.D. postdoctoral fellow.
“This tells us a lot about what is going on in the brains of people with Rett syndrome, autism or even schizophrenia,” said Chao.
Chao made the discovery by developing a mouse model that allowed scientists to remove MeCP2 from only the GABAergic neurons.
“This study taught us that an alteration in the signal from GABAergic neurons is sufficient to produce features of autism and other neuropsychiatric disorders,” said Dr. Huda Zoghbi, a Howard Hughes Medical Institute investigator and director of the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital.
Chao, a Ph.D student in Zoghbi’s laboratory, added, “We did this study thinking that perhaps all we would see was a few symptoms of Rett syndrome.”
“Strikingly, we saw that removing MeCP2 solely from GABAergic neurons reproduced almost all the features of Rett syndrome, including cognitive deficits, breathing difficulties, compulsive behavior, and repetitive stereotyped movements. The study tells us that MeCP2 is a key protein for the function of these neurons.”
After the scientists realized that the key factor was the GABAergic neurons, they wanted to know how the missing MeCP2 affected the function of these neurons. It was then that Chao figured out that losing MeCP2 caused the GABAergic neurons to release less GABA.
“A child is born healthy. She starts to grow and then begins to lose developmental milestones. Communication between neurons is impaired, in part due to reduced signals from GABAergic neurons.”
This study is published in the current issue of the journal Nature.
Source: Baylor College of Medicine
Pedersen, T. (2018). Brain Abnormality Linked to Psychiatric Disorders. Psych Central. Retrieved on April 1, 2020, from https://psychcentral.com/news/2010/11/14/brain-abnormality-linked-to-psychiatric-disorders/20786.html