Brain Abnormality Linked to Psychiatric Disorders

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Brain Abnormality Linked to Psychiatric Disorders

By Traci Pedersen Associate News Editor

Reviewed by M. Grohol, Psy.D. on November 13, 2010

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 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