Serotonin 2C receptor regulates reminiscence in mice and people: Implications for Alzheimer’s illness

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Researchers at Baylor Faculty of Medication, the College of Cambridge within the U.Okay. and participating establishments have proven that serotonin 2C receptor within the mind regulates reminiscence in folks and animal fashions. The findings, revealed within the magazine Science Advances, now not handiest supply new insights into the criteria taken with wholesome reminiscence but in addition in prerequisites related to reminiscence loss, like Alzheimer’s illness, and recommend novel avenues for remedy.

“Serotonin, a compound produced by way of neurons within the midbrain, acts as a neurotransmitter, passing messages between mind cells,” mentioned co-corresponding creator Dr. Yong Xu, professor of pediatrics—vitamin and affiliate director for fundamental sciences on the USDA/ARS Youngsters’s Diet Analysis Heart at Baylor.
“Serotonin-producing neurons achieve out to a couple of mind areas together with the hippocampus, a area very important for short- and long-term reminiscence.”
Serotonin communicates messages to mind cells by way of binding to receptors at the mobile floor, which sign the receiving mobile to hold on a definite job.
On this find out about, the Xu lab, with experience in fundamental and genetic animal research, and the human genetics lab of co-corresponding creator Dr. I. Sadaf Farooqi, professor of metabolism and medication on the College of Cambridge, excited about serotonin 2C receptors, that are abundantly provide within the mind’s ventral hippocampal CA1 area (vCA1), investigating the position of the receptor in reminiscence in people and animal fashions.
“We had in the past recognized 5 people wearing variants of the serotonin 2C receptor gene (HTR2C) that produce faulty types of the receptor,” Farooqi mentioned. “Folks with those uncommon variants confirmed important deficits on reminiscence questionnaires. Those findings led us to research the affiliation between HTR2C variants and reminiscence deficits in animal fashions.”

The staff genetically engineered mice to imitate the human mutation. When the researchers ran behavioral exams on those mice to guage their reminiscence, they discovered that each women and men with the non-functional gene confirmed diminished reminiscence recall in comparison with the unmodified animals.
“After we blended the human information and the mouse information, we discovered compelling proof connecting non-functional mutations of the serotonin receptor 2C with reminiscence deficits in people,” Xu mentioned.
The animal fashions additionally enabled the staff to dig deeper into how the receptor mediates reminiscence. They found out a mind circuit that starts within the midbrain the place serotonin-producing neurons are situated. Those neurons challenge to the vCA1 area, which has plentiful serotonin 2C receptors.
“When neurons within the midbrain attaining out to neurons within the vCA1 area unlock serotonin, the neurotransmitter binds to its receptor signaling those cells to make adjustments that assist the mind consolidate recollections,” Xu mentioned.
Importantly, the researchers additionally discovered that this serotonin-associated neural circuit is broken in a mouse type of Alzheimer’s illness. “The neural circuit within the Alzheimer’s illness animal type can not unlock enough serotonin into the vCA1 area that may want to bind to its receptor within the downstream neurons to sign the adjustments required to consolidate a reminiscence,” Xu mentioned.
On the other hand, it’s conceivable to avoid this loss of serotonin and immediately turn on the downstream serotonin receptor by way of administering a serotonin analog, lorcaserin, a compound that selectively turns on the serotonin 2C receptor in those cells.
“We examined this technique in our animal type and have been excited to search out that the animals handled with the serotonin analog stepped forward their reminiscence,” Xu mentioned. “We are hoping our findings inspire additional research to guage the worth of serotonin analogs within the remedy of Alzheimer’s illness.”

Additional information:
Hesong Liu et al, Neural circuits expressing the serotonin 2C receptor keep watch over reminiscence in mice and people, Science Advances (2024). DOI: 10.1126/sciadv.adl2675. www.science.org/doi/10.1126/sciadv.adl2675

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Baylor Faculty of Medication

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Serotonin 2C receptor regulates reminiscence in mice and people: Implications for Alzheimer’s illness (2024, June 28)
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