Summary: Researchers have found that the serotonin 2C receptor in the brain plays a critical role in regulating memory in humans and animal models. This discovery provides insights into conditions associated with memory loss, such as Alzheimer’s disease, and suggests new avenues of treatment.
Mutations in the serotonin 2C receptor gene cause memory deficits, but serotonin analogs such as lorcaserin can improve memory by activating these receptors. This discovery opens the door to potential new treatments for Alzheimer’s and other memory-related disorders.
Key facts:
- Serotonin 2C receptors are critical for memory consolidation.
- Mutations in the serotonin 2C receptor gene lead to memory deficits.
- Serotonin analogs may improve memory in Alzheimer’s models.
Source: Baylor College of Medicine
Researchers at Baylor College of Medicine, the University of Cambridge in the UK and collaborating institutions have found that the serotonin 2C receptor in the brain regulates memory in humans and animal models.
The findings are published in the journal scientific advances, Not only will they provide new insights into what’s involved in healthy memory, but also into conditions associated with memory loss, such as Alzheimer’s disease, and suggest new avenues for treatment.
“Serotonin, a compound produced by neurons in the midbrain, acts as a neurotransmitter to transmit messages between brain cells,” said co-corresponding author Dr. Yong Shu, professor of pediatrics – associate director of nutrition and basic sciences at the USDA/ARS Pediatric Nutrition Research Center at Baylor.
“Serotonin-producing neurons reach many brain regions, including the hippocampus, which is important for short- and long-term memory.”
Serotonin sends messages to brain cells by binding to receptors on the cell surface, signaling the receptor cell to perform a specific activity. In this study, Xu’s lab has expertise in basic and genetic animal studies and Dr. Sadaf Faruqi, a professor of metabolism and medicine at the University of Cambridge, whose human genetics lab focused on the serotonin 2C receptor. The receptor, which is predominantly located in the ventral hippocampal CA1 region (vCA1) of the brain, has investigated its role in memory in humans and animal models.
“We have previously identified five individuals who carry variants of the serotonin 2C receptor gene.HTR2C) that produce defective receptor forms,” Faruqi said.
“People with these rare variants show significant deficits on memory questionnaires. These findings led us to investigate the relationship between them HTR2C Differences and memory deficits in animal models.
The team genetically engineered mice to mimic the human mutation. When the researchers conducted behavioral tests on these mice to assess their memory, they found that both males and females with the disabled gene had reduced memory compared to non-mutated animals.
“By combining human data and mouse data, we found compelling evidence linking inactivating mutations of serotonin receptor 2C to memory impairment in humans,” Xu said.
Animal models also allowed the team to further investigate how a receptor transmits memory. They discovered a brain circuit that begins in the midbrain, where the neurons that produce serotonin are located. These neurons project to the vCA1 region, which has an abundance of serotonin 2C receptors.
“When the neurons in the midbrain reach the neurons in the vCA1 region and release serotonin, the neurotransmitter binds to the receptor, and these cells make changes that help the brain consolidate memories,” he said.
Importantly, the researchers also found that this serotonin-related neural circuit was affected in a mouse model of Alzheimer’s disease.
“The neural circuit in the Alzheimer’s disease animal model cannot release enough serotonin in the vCA1 region to signal the changes needed to consolidate memory, which needs to bind to receptors in downstream neurons,” Xu said.
However, it is possible to overcome this serotonin deficiency by directly activating the downstream serotonin receptor, and the serotonin analog lorcaserin can be used to selectively activate the serotonin 2C receptor in these cells.
“We tested this strategy in our animal model and were very pleased to find that animals treated with serotonin analogs improved their memory,” he said.
“We hope that our findings will encourage further studies to evaluate the value of serotonin analogs in the treatment of Alzheimer’s disease.”
Other contributors to this work include Hesong Liu, Yang He, Hailan Liu, Bass Brewers, Nayin, Catherine Lawler, Julia M. Keogh, Ilana Henning, Dong-Ki Lee, Meng Yu, Longlong Tu, Nan Zhang, Christine M. They include Conde. , Junying Han, Zili Yan, Nikolas A. Scarcelli, Lan Liao, Jianming Xu, Qingchun Tong, Hui Zheng, Zheng Sun, Yongjie Yang, Chunmei Wang and Yanlin He. The authors are affiliated with one of the following institutions: Baylor College of Medicine, Texas Children’s Hospital, University of Cambridge, Texas Health Science Center at Houston, and Louisiana State University.
So memory and neuroscience research news
Author: Taylor Barnes
Source: Baylor College of Medicine
Contact: Taylor Barnes – Baylor College of Medicine
Image: Image credited to Neuroscience News.
Preliminary study: Open Access.
“Neuronal circuits expressing the serotonin 2C receptor regulate memory in mice and humans.” by Yong Shu et al Advances in science
Draft
Neuronal circuits expressing the serotonin 2C receptor regulate memory in mice and humans.
Memory loss is a hallmark of Alzheimer’s disease (AD). Post-mortem studies in rats and humans suggest that serotonin (5-hydroxytryptamine, 5-HT) plays a role in memory, but the underlying mechanism is unknown. Here, the 5-HT 2C receptor (5-HT2CR) Managing memory.
Transgenic mice expressing their bodies HTR2C Mutations in hippocampal ventral CA1 (vCA1) neurons show impaired plasticity and reduced memory. Additionally, 5-HT neurons project to and innervate vCA1 neurons.
Disruption of 5-HT synthesis or deletion of 5-HT in vCA1-projecting neurons2CRs impairs neural plasticity and memory in vCA1. We show that selective 5-HT2CR agonist, lorcaserin, improves synaptic plasticity and memory in AD mouse model.
In sum, we show that hippocampal 5-HT.2CR signaling regulates memory, which may inform the use of 5-HT2CR agonists in the treatment of dementia.