PERfect Day: reversible and dose‐dependent control of circadian time‐keeping in the mouse suprachiasmatic nucleus by translational switching of PERIOD2 protein expression DOI Creative Commons
David McManus, Andrew P. Patton, Nicola J. Smyllie

et al.

European Journal of Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 19, 2024

Abstract The biological clock of the suprachiasmatic nucleus (SCN) orchestrates circadian (approximately daily) rhythms behaviour and physiology that underpin health. SCN cell‐autonomous time‐keeping revolves around a transcriptional/translational feedback loop (TTFL) within which PERIOD (PER1,2) CRYPTOCHROME (CRY1,2) proteins heterodimerise suppress trans‐activation their encoding genes ( Per1,2 ; Cry1,2 ). To explore its contribution to time‐keeping, we used adeno‐associated virus–mediated translational switching express PER2 (tsPER2) in organotypic slices carrying bioluminescent TTFL reporters. Translational requires provision non‐canonical amino acid, alkyne lysine (AlkK), for protein expression. Correspondingly, AlkK, but not vehicle, induced constitutive expression tsPER2 neurons reversibly dose‐dependently suppressed pPer1 ‐driven transcription PER‐deficient Per1 , 2 ‐null) SCN, illustrating potency negative regulation TTFL. Constitutive tsPER2, however, failed initiate oscillations arrhythmic SCN. In rhythmic, PER‐competent AlkK reduced amplitude PER2‐reported as inhibition by progressively damped also lengthened period neuronal calcium rhythms. Following wash‐out remove regained period. Furthermore, retained pre‐washout phase: removal did phase‐shift Given tsCRY1 can regulate period, reset phase CRY‐deficient these results reveal overlapping distinct properties CRY1 emphasise utility functions proteins.

Language: Английский

Circadian Mechanisms in Brain Fluid Biology DOI Open Access
Velia S. Vizcarra, Ryann M. Fame, Lauren M. Hablitz

et al.

Circulation Research, Journal Year: 2024, Volume and Issue: 134(6), P. 711 - 726

Published: March 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.

Language: Английский

Citations

6
Distinct circuits and molecular targets of the paraventricular hypothalamus decode visceral and somatic pain DOI Creative Commons
Yongchang Li,

Fu‐Chao Zhang,

Di Li

et al.

Neuron, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

Citations

6
Neuronal and glial vulnerability of the suprachiasmatic nucleus in tauopathies: evidence from human studies and animal models DOI Creative Commons
Gowoon Son, Thomas C. Neylan, Lea T. Grinberg

et al.

Molecular Neurodegeneration, Journal Year: 2024, Volume and Issue: 19(1)

Published: Jan. 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.

Language: Английский

Citations

4
Targeting vulnerable microcircuits in the ventral hippocampus of male transgenic mice to rescue Alzheimer-like social memory loss DOI Creative Commons
Huiyang Lei, Guilin Pi, Ting He

et al.

Military Medical Research, Journal Year: 2024, Volume and Issue: 11(1)

Published: March 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.

Language: Английский

Citations

4
Transcriptomic Plasticity of the Circadian Clock in Response to Photoperiod: A Study in Male Melatonin-Competent Mice DOI Creative Commons
Olivia Cox, Manuel A. Giannoni‐Guzmán, Jean‐Philippe Cartailler

et al.

Journal of Biological Rhythms, Journal Year: 2024, Volume and Issue: 39(5), P. 423 - 439

Published: Aug. 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

Language: Английский

Citations

4
Intestinal Foxl1+ cell-derived CXCL12 maintains epithelial homeostasis by modulating cellular metabolism DOI

Mayu Yagita-Sakamaki,

Takayoshi Ito, Taiki Sakaguchi

et al.

International Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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

Language: Английский

Citations

0
The Intricate Relationship Between Circadian Rhythms and Gastrointestinal Peptides in Obesity DOI
Filipe M. Ribeiro,

Luiz Arnaldo,

Lana Passos

et al.

Peptides, Journal Year: 2025, Volume and Issue: unknown, P. 171356 - 171356

Published: Feb. 1, 2025

Language: Английский

Citations

0
Selective changes in vasopressin neurons and astrocytes in the suprachiasmatic nucleus of Prader–Willi syndrome subjects DOI Creative Commons
Felipe Corrêa‐da‐Silva, Jari B. Berkhout,

PC Schouten

et al.

Journal of Neuroendocrinology, Journal Year: 2025, Volume and Issue: unknown

Published: March 8, 2025

The hypothalamic suprachiasmatic nucleus (SCN) hosts the central circadian pacemaker and regulates daily rhythms in physiology behavior. SCN is composed of peptidergic neuron populations expressing arginine vasopressin (AVP) vasoactive intestinal polypeptide (VIP), as well glial cells. Patients with Prader-Willi Syndrome (PWS) commonly experience disturbances, which are particularly evident their sleep/wake patterns. Using publicly available single-cell RNA sequencing data, we assessed cell-type specificity PWS-causative genes murine SCN, revealed differential presence PWS-related neural subpopulations. We then investigated neurons cells using immunohistochemistry postmortem hypothalami PWS subjects matched controls. profiled characterized by AVP VIP, astroglia fibrillary acid protein (GFAP), microglia marked ionized calcium-binding adapter molecule 1 (Iba1) NADPH oxidase 2 (NOX2). Our analysis an increased total number, neuronal density, relative staining intensity AVP-containing compared to controls while VIP-containing were unaltered. In contrast, GFAP-expressing astroglial significantly lower subjects. Moreover, did not detect any differences between Collectively, our findings show that selectively affects astrocytes SCN. As each these cell can affect rhythmicity biological clock machinery, disruption may contribute disturbances patients PWS.

Language: Английский

Citations

0
Ticking Brain: Circadian Rhythm as a New Target for Cerebroprotection DOI

Shuaili Xu,

Milan Jia,

Jiaqi Guo

et al.

Stroke, Journal Year: 2024, Volume and Issue: 55(9), P. 2385 - 2396

Published: July 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

Language: Английский

Citations

3
Dysregulation of the Suprachiasmatic Nucleus Disturbs the Circadian Rhythm and Aggravates Epileptic Seizures by Inducing Hippocampal GABAergic Dysfunction in C57BL/6 Mice DOI
Xiaoshan Liang, Xiaotao Liang,

Yun-Yan Zhao

et al.

Journal of Pineal Research, Journal Year: 2024, Volume and Issue: 76(5)

Published: July 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.

Language: Английский

Citations

3