Balancing trophic and apoptotic cues is critical for development and regeneration of neuronal circuits.
SorCS2 is a single-chain receptor in CNS neurons but is cleaved into a two-chain variant in PNS glia
..we identify SorCS2 as a proneurotrophin (proNT) receptor, mediating both trophic and apoptotic signals in conjunction with p75 NTR
SorCS2- or p75 NTR-deficient in mice caused reduced dopamine levels and metabolism and dopaminergic hyperinnervation of the frontal cortex.
SorCS2 knockouts display dopaminergic hyperinnervation and an ADHD-like behavior.
“If the gene is defective, it’s 100 percent certain that it will lead to ADHD-like symptoms in mice. But humans also have this gene and it has been suspected that it could be involved in the development of ADHD in people. The gene prevents the nerve cells in the brain’s reward system from creating the right contacts and communicating properly.. We could see that this gene is necessary for the cells’ transmitters to stop growing when they reach each other. Only few nerve cells made the right contact.
The gene in question is called sorcs2, and if this gene is defective, the brain cells do not create an important protein that aids the dopamine cells in reaching each other, and that prevents the cells from communicating with the transmitter substance dopamine.
Dopamine is related to learning and rewarding; it motivates us for a certain behaviour and rewards us when we succeed. It is meant to promote behaviour that promotes our welfare and survival. Without dopamine it would be much harder to learn from our surroundings. We wouldn’t know in the same way what meaningful behaviour is.”“At the same time, the absence of dopamine also causes attention to be more scattered and sporadic. And that’s what the researchers have found in the mice that have the defective gene.
It’s long been assumed that ADHD in people is connected to a disturbance in the dopaminergic system [also know as the reward system]. So when researchers show that this gene contributes to the maintenance of the dopaminergic system in mice, and that gene is found in people, too, it would seem that there may be something to it, ADHD is a complex condition and research suggests that it can be caused by genetic predisposition as well as the surroundings and what goes on in early childhood. The question is how many of the people who are diagnosed with ADHD have a defect in this specific gene.
The Yale researchers worked with scientists in Denmark. The investigators found variants in the SORCS2 gene linked to the severity of alcohol withdrawal in people of European ancestry. Roughly one in 10 of them carries the variants, the findings showed. The identified gene variants could affect the ability of heavy drinkers to adjust to the abrupt elimination of alcohol. Heavy drinkers can develop shakes, nausea, headaches, anxiety and changes in blood pressure when going through alcohol withdrawal. In extreme cases, people could have seizures, the study authors explained.