summary: Researchers have discovered that serotonin 2C receptors in the brain play a key role in regulating memory in both humans and animal models. This groundbreaking discovery provides insight into conditions associated with memory loss, such as Alzheimer’s disease, and suggests new therapeutic pathways.
Mutations in the serotonin 2C receptor gene lead to memory impairment, but serotonin analogues such as lorcaserin may be able to improve memory by activating these receptors. This discovery opens the door to potential new treatments for Alzheimer’s disease and other memory-related disorders.
Key Facts:
- Serotonin 2C receptors are essential for memory consolidation.
- Mutations in the serotonin 2C receptor gene cause memory impairment.
- Serotonin analogues can improve memory in models of Alzheimer’s disease.
sauce: Baylor College of Medicine
Researchers from Baylor College of Medicine, the University of Cambridge, and collaborating institutions in the UK have found that serotonin 2C receptors in the brain control memory in humans and animal models.
The findings, published in the journal Scientific progress, It will provide new insights into factors involved in healthy memory as well as conditions associated with memory loss, such as Alzheimer’s disease, and suggest new treatment approaches.
“Serotonin, a compound produced by neurons in the midbrain, acts as a neurotransmitter, transmitting messages between brain cells,” said co-corresponding author Yong Xu, PhD, professor of pediatric nutrition and associate director for basic sciences at the USDA/Agricultural Research Service Child Nutrition Research Center at Baylor University.
“Serotonin-producing neurons are spread across multiple brain regions, including the hippocampus, a region essential for short-term and long-term memory.”
Serotonin transmits messages to brain cells by binding to receptors on the cell surface, which then signal the receiving cell to continue a specific activity. In this study, the Xu lab, with expertise in basic and genetic research in animals, and the human genetics lab of co-corresponding author I. Sadaf Farooqui, PhD, Professor of Metabolic Medicine at the University of Cambridge, focused on serotonin 2C receptors, which are abundant in the ventral hippocampal CA1 region (vCA1) of the brain, to investigate the role of the receptor in memory in humans and animal models.
“We previously identified five individuals with mutations in the serotonin 2C receptor gene (HTR2C) produces defective receptors,” Farooqui says.
“People with these rare mutations showed significant deficits in memory questionnaires. These findings lead us to HTR2C Mutations and Memory Impairment in Animal Models.”
The team genetically engineered mice to mimic the human mutation, and when the researchers performed behavioral tests to assess the mice’s memory, they found that both males and females with the non-functional gene had impaired memory compared to non-engineered mice.
“By combining our human and mouse data, we found compelling evidence linking dysfunctional mutations in serotonin receptor 2C to memory impairment in humans,” Xu said.
The animal model allowed the team to delve deeper into how the receptor mediates memory. They discovered a brain circuit that begins in the midbrain, where serotonin-producing neurons reside. These neurons project to the vCA1 region, which is rich in serotonin 2C receptors.
“When neurons in the midbrain reach neurons in the vCA1 region, the neurotransmitter releases serotonin, which binds to its receptors and causes changes in these cells, signaling them to help the brain consolidate the memory,” Xu said.
Importantly, the researchers also found that this serotonin-related neural circuitry was damaged in mouse models of Alzheimer’s disease.
“The neural circuitry in animal models of Alzheimer’s disease is unable to release enough serotonin into the vCA1 region to bind to receptors on downstream neurons to signal the changes needed to consolidate memories,” Xu said.
However, by administering the serotonin analogue lorcaserin, a compound that selectively activates the serotonin 2C receptors in these cells, it is possible to circumvent this serotonin deficiency and directly activate downstream serotonin receptors.
“We tested this strategy in animal models and were excited to find that animals given the serotonin analogues had improved memory,” Xu said.
“We hope that our findings will encourage further research to evaluate the value of serotonin analogues in treating Alzheimer’s disease.”
Other contributors to this study include Hesong Liu, Yang He, Hailan Liu, Bas Brouwers, Na Yin, Katherine Lawler, Julia M. Keogh, Elana Henning, Dong-Kee Lee, Meng Yu, Longlong Tu, Nan Zhang, Kristine M. Conde, Junying Han, Zili Yan, Nikolas A. Scarcelli, Lan Liao, Jianming Xu, Qingchun Tong, Hui Zheng, Zheng Sun, Yongjie Yang, and Chunmei Wang. and Yanlin He. The authors are affiliated with Baylor College of Medicine, Texas Children’s Hospital, University of Cambridge, University of Texas Health Science Center at Houston, and Louisiana State University.
About this Memory and Neuroscience Research News
author: Taylor Barnes
sauce: Baylor College of Medicine
contact: Taylor Barnes – Baylor College of Medicine
image: Image courtesy of Neuroscience News
Original Research: Open access.
“Serotonin 2C receptor-expressing neural circuits regulate memory in mice and humansYong Xu et al. Scientific advances
Abstract
Serotonin 2C receptor-expressing neural circuits regulate memory in mice and humans
Memory decline is a hallmark of Alzheimer’s disease (AD). Rodent experiments and human postmortem studies suggest that serotonin (5-hydroxytryptamine, 5-HT) plays a role in memory, but the underlying mechanisms are unclear. Here, we investigate how serotonin (5-HT2C receptors) (5-HT2CR) Involved in regulating memory.
Transgenic mice expressing humanized genes HTR2C The mutation impairs the plasticity of hippocampal ventral CA1 (vCA1) neurons, impairing memory. Furthermore, 5-HT neurons project to and synapse onto vCA1 neurons.
Inhibition of 5-HT synthesis or depletion of 5-HT in vCA1-projecting neurons2CR in vCA1 inhibits neuroplasticity and memory. Selective 5-HT2CThe R agonist lorcaserin improves synaptic plasticity and memory in AD mouse models.
Cumulatively, we found that hippocampal 5-HT2CR signaling regulates memory and may influence 5-HT use.2CR agonists in the treatment of dementia.