by Henry H. Ong
Abnormal signaling of dopamine – an important neurotransmitter – is implicated in brain disorders such as schizophrenia. Knowing the underlying molecular mechanisms may lead to novel treatments for schizophrenia.
Olga Dadalko, Aurelio Galli, Ph.D., Kevin Niswender, M.D., Ph.D., and colleagues have reported a promising new mechanism of disrupted dopamine signaling in the June 10 issue of The Journal of Neuroscience.
Their previous work showed insulin-resistance arising from diabetes or obesity leads to dopamine dysfunction through impairment of the enzyme Akt, although the molecular mechanism is not known. In their current work, they investigate the protein complex mTORC2, a known regulator of Akt, as a possible mechanism.
Using a mouse model, the investigators show abnormal mTORC2 signaling in the dorsal striatum brain region leads to hyperactivity and amphetamine hypersensitivity, hallmarks of schizophrenia animal models, caused in part by increased D2 dopamine receptor expression and activity of the enzyme ERK1/2.
This work strongly implicates dysfunction of mTORC2 signaling as a possible molecular mechanism of schizophrenia that warrants further investigation.
This research was supported by National Institutes of Health Grant DA038058.
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