Distinct circuits and molecular targets of the paraventricular hypothalamus decode visceral and somatic pain

Neuron, Год журнала: 2024, Номер unknown

Опубликована: Сен. 1, 2024

Язык: Английский

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Circadian Mechanisms in Brain Fluid Biology

Circulation Research, Год журнала: 2024, Номер 134(6), С. 711 - 726

Опубликована: Март 14, 2024

The brain is a complex organ, fundamentally changing across the day to perform basic functions like sleep, thought, and regulating whole-body physiology. This requires symphony of nutrients, hormones, ions, neurotransmitters more be properly distributed maintain homeostasis throughout 24 hours. These solutes are both by blood cerebrospinal fluid. Cerebrospinal fluid contents distinct from general circulation because regulation at barriers including choroid plexus, glymphatic system, blood-brain barrier. In this review, we discuss overlapping circadian (≈24-hour) rhythms in biology barriers. Our goal for reader gain fundamental understanding alongside an interactions between these fluids timing system. Ultimately, review will provide new insight into how alterations finely tuned clocks may lead pathology.

Язык: Английский

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Neuronal and glial vulnerability of the suprachiasmatic nucleus in tauopathies: evidence from human studies and animal models

Molecular Neurodegeneration, Год журнала: 2024, Номер 19(1)

Опубликована: Янв. 10, 2024

Tauopathies, a group of neurodegenerative diseases that includes Alzheimer's disease, commonly lead to disturbances in sleep-wake patterns and circadian rhythm disorders. The rhythm, recurring 24-hour cycle governing human biological activity, is regulated by the hypothalamic suprachiasmatic nucleus (SCN) endogenous transcriptional-translational feedback loops. Surprisingly, little attention has been given investigating tauopathy-driven neuropathology SCN repercussions gene dysfunction brain affected tauopathies. This review aims provide an overview current literature on vulnerability tauopathies humans. Emphasis placed elucidating neuronal glial changes contributing widespread disruption molecular clock. Furthermore, this identifies areas knowledge requiring further investigation.

Язык: Английский

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Targeting vulnerable microcircuits in the ventral hippocampus of male transgenic mice to rescue Alzheimer-like social memory loss

Military Medical Research, Год журнала: 2024, Номер 11(1)

Опубликована: Март 11, 2024

Abstract Background Episodic memory loss is a prominent clinical manifestation of Alzheimer’s disease (AD), which closely related to tau pathology and hippocampal impairment. Due the heterogeneity brain neurons, specific roles different neurons in terms their sensitivity accumulation contribution AD-like social remain unclear. Therefore, further investigation necessary. Methods We investigated effects by Tandem mass tag proteomic phosphoproteomic analysis, behavioural tests, electrophysiology, immunofluorescence staining vivo optical fibre recording GCaMP6f iGABASnFR. Additionally, we utilized optogenetics administered ursolic acid (UA) via oral gavage examine these agents on mice. Results The results analyses revealed characteristics ventral CA1 (vCA1) under both physiological conditions pathology. As progressively accumulated, vCA1, especially its excitatory parvalbumin (PV) were fully filled with mislocated phosphorylated (p-Tau). This finding was not observed for dorsal (dCA1). overexpression human (hTau) PV mimicked accumulation, significantly inhibited neuronal excitability suppressed distinct discrimination-associated firings within vCA1. Photoactivating vCA1 at rhythms time windows efficiently ameliorated tau-impaired memory. Notably, 1 month UA administration decreased autophagy transcription factor EB (TFEB)-dependent manner restored microcircuit ameliorate Conclusion study elucidated protein phosphoprotein networks between dCA1 highlighted susceptibility accumulation. our novel findings regarding efficacy reducing load targeting may provide promising strategy treating AD future.

Язык: Английский

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Dysregulation of the Suprachiasmatic Nucleus Disturbs the Circadian Rhythm and Aggravates Epileptic Seizures by Inducing Hippocampal GABAergic Dysfunction in C57BL/6 Mice

Journal of Pineal Research, Год журнала: 2024, Номер 76(5)

Опубликована: Июль 26, 2024

ABSTRACT The interplay between circadian rhythms and epilepsy has gained increasing attention. suprachiasmatic nucleus (SCN), which acts as the master pacemaker, regulates physiological behavioral through its complex neural networks. However, exact role of SCN Bmal1 gene in development remains unclear. In this study, we utilized a lithium–pilocarpine model to induce mice simulated disturbances by creating lesions specifically knocking out neurons. We observed that pilocarpine‐induced epileptic experienced increased daytime seizure frequency, irregular oscillations core body temperature, alterations both hippocampus. Additionally, there was enhanced activation GABAergic projections from Notably, intensified activity, concomitant with hippocampal neuronal damage signaling impairment. Further analyses using Gene Expression Omnibus database set enrichment analysis indicated reduced expression patients medial temporal lobe epilepsy, potentially affecting GABA receptor pathways. Targeted deletion neurons exacerbated seizures pathology well diminished efficacy. These results underscore crucial modulating function hippocampus, aggravating severity seizures. This study provides significant insights into how rhythm can influence dysfunction highlighting therapeutic potential targeting within it management.

Язык: Английский

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Transcriptomic Plasticity of the Circadian Clock in Response to Photoperiod: A Study in Male Melatonin-Competent Mice

Journal of Biological Rhythms, Год журнала: 2024, Номер 39(5), С. 423 - 439

Опубликована: Авг. 2, 2024

Seasonal daylength, or circadian photoperiod, is a pervasive environmental signal that profoundly influences physiology and behavior. In mammals, the central clock resides in suprachiasmatic nuclei (SCN) of hypothalamus where it receives retinal input synchronizes, entrains, organismal behavior to prevailing light cycle. The process entrainment induces sustained plasticity SCN, but molecular mechanisms underlying SCN are incompletely understood. Entrainment different photoperiods persistently alters timing, waveform, period, resetting properties its driven rhythms. To elucidate novel candidate genes for photoperiod plasticity, we performed RNA sequencing on whole dissected from mice raised long (light:dark [LD] 16:8) short (LD 8:16) photoperiods. Fewer rhythmic were detected subjected general, timing gene expression rhythms was advanced 4-6 h. However, few showed significant delays, including

Язык: Английский

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Ticking Brain: Circadian Rhythm as a New Target for Cerebroprotection

Stroke, Год журнала: 2024, Номер 55(9), С. 2385 - 2396

Опубликована: Июль 16, 2024

Circadian rhythm is a master process observed in nearly every type of cell throughout the body, and it macroscopically regulates daily physiology. Recent clinical trials have revealed effects circadian variation on incidence, pathophysiological processes, prognosis acute ischemic stroke. Furthermore, core clock genes, cell-autonomous pacemakers rhythm, affect neurovascular unit-composing cells nonparallel manner after same processes ischemia/reperfusion. In this review, we discuss influence rhythms genes each unit

Язык: Английский

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Intestinal Foxl1+ cell-derived CXCL12 maintains epithelial homeostasis by modulating cellular metabolism

International Immunology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

Abstract Several mesenchymal cell populations are known to regulate intestinal stem (ISC) self-renewal and differentiation. However, the influences of signaling mediators derived from cells other than ISC niche factors on epithelial homeostasis remain poorly understood. Here, we show that host microbial metabolites, such as taurine gamma-aminobutyric acid (GABA), act PDGFRαhigh Foxl1high sub-epithelial their transcription. In addition, found CXC chemokine ligand 12 (CXCL12) produced induces cycle arrest through modulation mevalonate–cholesterol synthesis pathway, which suppresses tumor progression in ApcMin/+ mice. We identified highly express CXCL12 among colonic cells. Foxl1-cre; Cxcl12f/f mice showed an increased number Ki67+ CXCL12-induced Ca2+ mobilization facilitated phosphorylation AMPK cells, inhibits maturation sterol regulatory element-binding proteins (SREBPs) responsible for mevalonate pathway activation. Furthermore, Cxcl12 deficiency Foxl1-expressing promoted development small large intestines Collectively, these results demonstrate secreted manipulates metabolism, links prevention

Язык: Английский

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Targeting GABA signaling in type 1 diabetes and its complications- an update on the state of the art

Pharmacological Reports, Год журнала: 2025, Номер unknown

Опубликована: Янв. 21, 2025

Язык: Английский

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The Intricate Relationship Between Circadian Rhythms and Gastrointestinal Peptides in Obesity

Peptides, Год журнала: 2025, Номер unknown, С. 171356 - 171356

Опубликована: Фев. 1, 2025

Язык: Английский

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