Deciphering the Functions of Raphe-Hippocampal Serotonergic and Glutamatergic Circuits and Their Deficits in Alzheimer's Disease.

Int J Mol Sci

Hubei Clinical Research Center for Alzheimer's Disease, Brain Science and Advanced Technology Institute, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China.

Published: January 2025


Category Ranking

98%

Total Visits

921

Avg Visit Duration

2 minutes

Citations

20

Article Abstract

Subcortical innervation of the hippocampus by the raphe nucleus is essential for emotional and cognitive control. The two major afferents from raphe to hippocampus originate from serotonergic and glutamatergic neurons, of which the serotonergic control of hippocampal inhibitory network, theta activity, and synaptic plasticity have been extensively explored in the growing body of literature, whereas those of glutamatergic circuits have received little attention. Notably, both serotonergic and glutamatergic circuits between raphe and hippocampus are disrupted in Alzheimer's disease (AD), which may contribute to initiation and progression of behavioral and psychological symptoms of dementia. Thus, deciphering the mechanism underlying abnormal raphe-hippocampal circuits in AD is crucial to prevent dementia-associated emotional and cognitive symptoms. In this review, we summarize the anatomical, neurochemical, and electrophysiological diversity of raphe nuclei as well as the architecture of raphe-hippocampal circuitry. We then elucidate subcortical control of hippocampal activity by raphe nuclei and their role in regulation of emotion and cognition. Additionally, we present an overview of disrupted raphe-hippocampal circuits in AD pathogenesis and analyze the available therapies that can potentially be used clinically to alleviate the neuropsychiatric symptoms and cognitive decline in AD course.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11818420PMC
http://dx.doi.org/10.3390/ijms26031234DOI Listing

Publication Analysis

Top Keywords

serotonergic glutamatergic
12
glutamatergic circuits
12
alzheimer's disease
8
emotional cognitive
8
raphe hippocampus
8
control hippocampal
8
raphe-hippocampal circuits
8
raphe nuclei
8
circuits
5
raphe
5

Similar Publications

Adsorption behavior and neurotoxic synergy of thallium and polystyrene microplastics in Caenorhabditis elegans.

Aquat Toxicol

September 2025

State Environmental Protection Key Laboratory of Environmental Pollution Health Risk Assessment, South China Institute of Environmental Sciences, Ministry of Ecology and Environment, Guangzhou 510655, China. Electronic address:

Microplastics (MPs) have emerged as ubiquitous environmental contaminants, while thallium (Tl), a highly toxic metalloid, is gaining attention as a novel pollutant due to its increasing release from electronic waste and mining activities. These pollutants frequently coexist in aquatic environments; however, their combined effects at environmentally relevant concentrations remain poorly understood. In this study, the adsorption behavior and joint neurotoxicity of polystyrene (PS) microplastics and Tl were systematically evaluated using Caenorhabditis elegans as a model organism.

View Article and Find Full Text PDF

Biological, Psychosocial, and Microbial Determinants of Childhood-Onset Obsessive-Compulsive Disorder: A Narrative Review.

Children (Basel)

August 2025

Departamento de Microbiología, Universidad de Málaga, 29071 Málaga, Spain.

The etiology of obsessive-compulsive disorder (OCD) remains incompletely understood, but it is widely recognized as the result of a complex interplay among multiple contributing mechanisms, often emerging during childhood. This narrative review synthesizes current evidence on the etiology of childhood-onset OCD, with particular focus on whether GM alterations are involved in the pathophysiological mechanisms underlying the disorder. Specifically, the review first examines both biological and psychosocial determinants of OCD, and then explores the role of the gut microbiome (GM), including the potential of psychobiotics as a novel therapeutic approach.

View Article and Find Full Text PDF

Neuroendocrine Effects of Hyperprolactinemia: Focus on Dopamine and Serotonin Systems.

Endocr Metab Immune Disord Drug Targets

August 2025

Formulation Scientist(R&D), LNK International Inc., Hauppauge, New York, 11788, United States.

Hyperprolactinemia is characterized by unusually high levels of prolactin, a hormone primarily known for regulating reproductive functions. However, studies have shown that prolactin has also a significant impact on various neurotransmitter systems in the brain. This review examined the intricate relationship between hyperprolactinemia and neurotransmission, with a particular emphasis on the dopaminergic and serotonergic systems.

View Article and Find Full Text PDF

Endocannabinoids, depression, and treatment resistance: Perspectives on effective therapeutic interventions.

Psychiatry Res

August 2025

Department of Neuroscience, Imaging and Clinical Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti-Pescara, Italy; Department of Pharmacy, Pharmacology and Clinical Sciences, University of Hertfordshire, Herts, UK.

Depression is a prevalent and heterogeneous disorder with significant personal and social consequences. The rise of treatment-resistant depression (TRD) challenges traditional approaches and underscores the need for a broader neurobiological perspective. When monoaminergic modulation proves insufficient, clinical guidelines increasingly turn to non-monoaminergic interventions such as neuromodulation techniques and glutamatergic agents, which operate through distinct mechanisms.

View Article and Find Full Text PDF

Chlorpyrifos (CPF) is one of the most widely used pesticides globally, despite being strictly regulated and banned in several developed countries. It remains in use across many developing and underdeveloped nations. While its primary mechanism of action is acetylcholinesterase inhibition, multiple preclinical and clinical studies have reported developmental and cognitive alterations at lower doses that do not trigger this mechanism.

View Article and Find Full Text PDF