Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death among epilepsy patients, occurring even more frequently in cases with anti-epileptic drug resistance. Despite some advancements in characterizing SUDEP, the underlying mechanism remains incompletely understood. This review summarizes the latest advances in our understanding of the pathogenic mechanisms of SUDEP, in order to identify possible targets for the development of new strategies to prevent SUDEP. Based on our previous research along with the current literature, we focus on the role of sleep-disordered breathing (SDB) and its related neural mechanisms to consider the possible roles of monoaminergic neurons in the modulation of respiration during sleep and the occurrence of SUDEP. Overall, this review suggests that targeting the monoaminergic neurons is a promising approach to preventing SUDEP. The proposed roles of SDB and related monoaminergic neural mechanisms in SUDEP provide new insights for explaining the pathogenesis of SUDEP.
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http://dx.doi.org/10.1016/j.biopha.2022.112983 | DOI Listing |
Neurotox Res
January 2025
Molecular Neuropsychiatry Section, Intramural Research Program, NIH/ NIDA, 21224, Baltimore, MD, U.S.A.
To identify factors involved in methamphetamine (METH) neurotoxicity, we comprehensively searched for genes which were differentially expressed in mouse striatum after METH administration using differential display (DD) reverse transcription-PCR method and sequent single-strand conformation polymorphism analysis, and found two DD cDNA fragments later identified as mRNA of Nedd4 (neural precursor cell expressed developmentally downregulated 4) WW domain-binding protein 5 (N4WBP5), later named Nedd4 family-interacting protein 1 (Ndfip1). It is an adaptor protein for the binding between Nedd4 of ubiquitin ligase (E3) and target substrate protein for ubiquitination. Northern blot analysis confirmed drastic increases in Ndfip1 mRNA in the striatum after METH injections, and in situ hybridization histochemistry showed that the mRNA expression was increased in the hippocampus and cerebellum at 2 h-2 days, in the cerebral cortex and striatum at 18 h-2 days after single METH administration.
View Article and Find Full Text PDFJ Comp Neurol
January 2025
Graduate Program in Molecular and Systems Pharmacology, Emory University, Atlanta, Georgia, USA.
Glutamate delta receptor 1 (GluD1) is a unique synaptogenic molecule expressed at excitatory and inhibitory synapses. The lateral habenula (LHb), a subcortical structure that regulates negative reward prediction error and major monoaminergic systems, is enriched in GluD1. LHb dysfunction has been implicated in psychiatric disorders such as depression and schizophrenia, both of which are associated with GRID1, the gene that encodes GluD1.
View Article and Find Full Text PDFEnteroendocrine cells (EECs) are a rare cell type of the intestinal epithelium. Various subtypes of EECs produce distinct repertoires of monoamines and neuropeptides which modulate intestinal motility and other physiologies. EECs also possess neuron-like properties, suggesting a potential vulnerability to ingested environmental neurotoxicants.
View Article and Find Full Text PDFBrain Res
December 2024
Geriatric Department, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China. Electronic address:
Since the discovery of orexin/hypocretin, numerous studies have accumulated evidence demonstrating its key role in various aspects of neuromodulation, including addiction, motivation, and arousal. This paper focuses on the projection of orexin neurons to specific target brain regions through distinct neural pathways to regulate sleep and arousal. We provide a detailed discussion of the projection mechanisms of orexin neurons to downstream neurons, particularly emphasizing their activation of monoaminergic and cholinergic neurons associated with arousal.
View Article and Find Full Text PDFFASEB J
December 2024
Laboratory of Exercise Biochemistry and Neuroendocrinology, Institute of Health and Sport Sciences, University of Tsukuba, Tsukuba, Japan.
Exercise activates the dorsal hippocampus that triggers synaptic and cellar plasticity and ultimately promotes memory formation. For decades, these benefits have been explored using demanding and stress-response-inducing exercise at moderate-to-vigorous intensities. In contrast, our translational research with animals and humans has focused on light-intensity exercise (light exercise) below the lactate threshold (LT), which almost anyone can safely perform with minimal stress.
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