Conditions

ADHD Possibly Caused By A Miswiring Of Brain Region Linked To Dopamine And Addiction

ADHD
A team of neuroscientists who studied miswiring in the brain's reward system believe their findings may help explain ADHD. Photo courtesy of Shutterstock.

With recent advances in neuroimaging techniques, neuroscientists have made swift progression in recent years. Among their observations, the dopamine system, which prepares the brain to think and move, also functions to help the brain anticipate reward, and for this reason it has been identified in studies of addiction.

Now, a team of neuroscientists who designed a series of animal experiments to study miswiring in the brain's dopamine system believe findings from their experiments may increase understanding of the underlying causes of attention deficit hyperactivity disorder (ADHD). "This miswiring of dopaminergic neurons in mice results in hyperactivity and attention deficits," said Dr. Anders Nykjaer, a neuroscientist at Mayo Clinic in Florida and at Aarhus University in Denmark and the new study's senior investigator.

Dopaminergic neurons regulate pleasure, motivation, reward, and cognition, and for this reason scientists often investigate them when taking a close look at addiction and its effects on the brain. Yet, recent studies have implicated these same neurons in the development of ADHD. In an effort to better understand the development and regeneration of neuronal circuits, Nykjaer and his team began by examining the dopaminergic neurons. Soon, they uncovered a receptor system that is critical for correct wiring, during embryonic development, of the dopaminergic brain area.

The SorCS2 receptor operates as a molecular switch that seems to regulate opposing effects created by proBDNF, a neuronal growth factor that is commonly thought to support the survival of nerve cells. What ProBDNF actually does, though, is help select those cells that are most beneficial to the nervous system, while eliminating those that are less favorable. These opposing functions of ProBDNF, regulated by the molecular switch of SorCS2, fine-tune the neuronal network.

Exploring SorCS2 in experiments conducted on mice, Nykjaer and his colleagues discovered that some cells in mice deficient in SorCS2 are unresponsive to proBDNF and have dysfunctional contacts between dopaminergic neurons.

"SorCS2 is produced as a single-chain protein — one long row of amino acids — but it can be cut into two chains to perform a different function,” said Nykjaer in a press release. “While the single-chain receptor is essential to tell the neuron that it is time to stop growing, the two-chain form tells cells… to die when they should." Unfortunately, if damage occurs to a nerve in the peripheral nervous system, these cells will die, preventing efficient regeneration. Nykjaer and his team believe it may be possible to develop medicines to prevent this division of SorCS2 and prevent nerve damage while also thwarting resulting conditions, including, possibly, ADHD.

 

Source: Nykjaer A, Glerup S, Olsen D, et al. SorCS2 Regulates Dopaminergic Wiring and Is Processed into an Apoptotic Two-Chain Receptor in Peripheral Glia. Neuron. 2014.

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