Serotonin 2C receptor regulates memory in mice and folks: Implications for Alzheimer’s disease

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Researchers at Baylor Faculty of Treatment, the College of Cambridge within the U.Ok. and taking part institutions ranking confirmed that serotonin 2C receptor within the mind regulates memory in of us and animal units. The findings, printed within the journal Science Advances, no longer easiest provide unusual insights into the factors inquisitive about wholesome memory but moreover in prerequisites associated to memory loss, cherish Alzheimer’s disease, and counsel unusual avenues for cure.

“Serotonin, a compound produced by neurons within the midbrain, acts as a neurotransmitter, passing messages between mind cells,” acknowledged co-corresponding author Dr. Yong Xu, professor of pediatrics—weight loss program and partner director for classic sciences at the USDA/ARS Younger of us’s Nutrition Learn Center at Baylor.

“Serotonin-producing neurons reach out to more than one mind areas alongside side the hippocampus, a local a truly grand for transient- and prolonged-term memory.”

Serotonin communicates messages to mind cells by binding to receptors on the cell surface, which signal the receiving cell to persist with it a obvious process.

On this gape, the Xu lab, with expertise in classic and genetic animal review, and the human genetics lab of co-corresponding author Dr. I. Sadaf Farooqi, professor of metabolism and medicine at the College of Cambridge, centered on serotonin 2C receptors, which would possibly very nicely be abundantly cloak within the mind’s ventral hippocampal CA1 space (vCA1), investigating the position of the receptor in memory in folks and animal units.

“We had previously identified five participants carrying variants of the serotonin 2C receptor gene (HTR2C) that create immoral kinds of the receptor,” Farooqi acknowledged. “Of us with these uncommon variants showed essential deficits on memory questionnaires. These findings led us to analyze the affiliation between HTR2C variants and memory deficits in animal units.”

The crew genetically engineered mice to mimic the human mutation. When the researchers ran behavioral tests on these mice to imagine their memory, they chanced on that each and each males and females with the non-functional gene showed diminished memory design close when when in contrast with the unmodified animals.

“After we mixed the human files and the mouse files, we chanced on compelling proof connecting non-functional mutations of the serotonin receptor 2C with memory deficits in folks,” Xu acknowledged.

The animal units moreover enabled the crew to dig deeper into how the receptor mediates memory. They chanced on a mind circuit that begins within the midbrain the attach serotonin-producing neurons are situated. These neurons mission to the vCA1 space, which has abundant serotonin 2C receptors.

“When neurons within the midbrain reaching out to neurons within the vCA1 space open serotonin, the neurotransmitter binds to its receptor signaling these cells to shatter adjustments that support the mind consolidate memories,” Xu acknowledged.

Importantly, the researchers moreover chanced on that this serotonin-associated neural circuit is broken in a mouse model of Alzheimer’s disease. “The neural circuit within the Alzheimer’s disease animal model can’t open enough serotonin into the vCA1 space that could ought to bind to its receptor within the downstream neurons to signal the adjustments required to consolidate a memory,” Xu acknowledged.

Nonetheless, it is that you are going to be ready to imagine to avoid this lack of serotonin and at once activate the downstream serotonin receptor by administering a serotonin analog, lorcaserin, a compound that selectively activates the serotonin 2C receptor in these cells.

“We tested this blueprint in our animal model and were enraged to search out that the animals handled with the serotonin analog improved their memory,” Xu acknowledged. “We hope our findings support further review to imagine the ticket of serotonin analogs within the cure of Alzheimer’s disease.”

More files:
Hesong Liu et al, Neural circuits expressing the serotonin 2C receptor regulate memory in mice and folks, Science Advances (2024). DOI: 10.1126/sciadv.adl2675.

Serotonin 2C receptor regulates memory in mice and folks: Implications for Alzheimer’s disease (2024, June 28)
retrieved 29 June 2024

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