Summary: Researchers have discovered that the serotonin 2C receptor in the brain plays a crucial role in regulating memory in both humans and animals. The discovery offers insight into diseases associated with memory loss, such as Alzheimer’s disease, and suggests new avenues for treatment.
Mutations in the serotonin 2C receptor gene lead to memory deficits, but serotonin analogs like lorcaserin could improve memory by activating these receptors. This discovery opens the door to potential new therapies for Alzheimer’s disease and other memory-related disorders.
Highlights:
- Serotonin 2C receptors are essential for memory consolidation.
- Mutations in the serotonin 2C receptor gene lead to memory deficits.
- Serotonin analogues may improve memory in Alzheimer’s models.
Source: Baylor College of Medicine
Researchers from Baylor College of Medicine, the University of Cambridge in the United Kingdom, and collaborating institutions have shown that the serotonin 2C receptor in the brain regulates memory in humans and animal models.
The results, published in the journal Scientific progress, not only provide new insights into the factors 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, transmitting messages between brain cells,” said co-corresponding author Dr. Yong Xu, professor of pediatrics-nutrition and associate director of science. fundamentals at the USDA/ARS Child Nutrition Research Center at Baylor.
“Serotonin-producing neurons extend to several regions of the brain, including the hippocampus, a region essential for short- and long-term memory. »
Serotonin communicates messages to brain cells by binding to receptors on the cell surface, which signal the receiving cell to continue a certain activity. In this study, the Xu lab, with expertise in basic and animal genetic studies, and the human genetics lab of co-corresponding author Dr. I. Sadaf Farooqi, professor of metabolism and medicine at the University of Cambridge, focused on serotonin 2C receptors, which are abundantly present in the ventral hippocampal CA1 region of the brain (vCA1), investigating the receptor’s role in memory in humans and animal models.
“We previously identified five individuals carrying variants of the serotonin 2C receptor gene (HTR2C) that produce defective forms of the receptor,” Farooqi said.
“People with these rare variants showed significant deficits on memory questionnaires. These results led us to study the association between HTR2C “Memory Variants and Deficits in Animal Models.”
The team genetically modified mice to replicate the human mutation. When the researchers performed behavioral tests on the mice to assess their memory, they found that both males and females with the nonfunctional gene had reduced memory abilities compared to unmodified animals.
“When we combined human and mouse data, we found compelling evidence linking nonfunctional mutations in the serotonin 2C receptor to memory deficits in humans,” Xu said.
Animal models also 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 are located. These neurons project to the vCA1 region, which has abundant serotonin 2C receptors.
“When neurons in the midbrain that reach neurons in the vCA1 region release serotonin, the neurotransmitter binds to its receptor, signaling these cells to make changes that help the brain consolidate memories,” Xu said.
Importantly, researchers also found that this serotonin-associated neural circuit is damaged in a mouse model of Alzheimer’s disease.
“The neural circuit in the animal model of Alzheimer’s disease cannot release enough serotonin in the vCA1 region that would need to bind to its receptor in downstream neurons to signal the changes needed for memory consolidation,” Xu said.
However, it is possible to bypass this lack of serotonin and directly activate the downstream serotonin receptor by administering a serotonin analogue, lorcaserin, a compound that selectively activates the serotonin 2C receptor in these cells.
“We tested this strategy in our animal model and were pleased to find that animals treated with the serotonin analog improved their memory,” Xu said.
“We hope that our results will encourage further studies to evaluate the value of serotonin analogues in the treatment of Alzheimer’s disease.”
Other contributors to this work 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 . , 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, University of Texas Health Science Center at Houston, and Louisiana State University.
About this news in memory and neuroscience research
Author: Taylor Barnes
Source: Baylor College of Medicine
Contact: Taylor Barnes – Baylor School of Medicine
Picture: Image credited to Neuroscience News
Original research: Free access.
“Neural circuits expressing the serotonin 2C receptor regulate memory in mice and humans” by Yong Xu et al. Scientists progress
Abstract
Neural circuits expressing the serotonin 2C receptor regulate memory in mice and humans
Memory decline is a hallmark of Alzheimer’s disease (AD). Experiments in rodents and postmortem studies in humans suggest that serotonin (5-hydroxytryptamine, 5-HT) plays a role in memory, but the underlying mechanisms are unknown. Here, we investigate the role of the 5-HT 2C receptor (5-HT2CR) in the regulation of memory.
Transgenic mice expressing a humanized HTR2C Mutations exhibit impaired plasticity of ventral hippocampal CA1 (vCA1) neurons and reduced memory. Additionally, 5-HT neurons project to and synapse on vCA1 neurons.
Disruption of 5-HT synthesis in vCA1-projecting neurons or suppression of 5-HT2CRs in vCA1 impair neuronal plasticity and memory. We show that a selective 5-HT2CThe R agonist lorcaserin improves synaptic plasticity and memory in an AD mouse model.
Cumulatively, we demonstrate that hippocampal 5-HT2CR signaling regulates memory, which may inform 5-HT use2CR agonists in the treatment of dementia.