The Suprachiasmatic Nucleus at 50: Looking Back, Then Looking Forward

Journal of Biological Rhythms, Journal Year: 2024, Volume and Issue: 39(2), P. 135 - 165

Published: Feb. 16, 2024

It has been 50 years since the suprachiasmatic nucleus (SCN) was first identified as central circadian clock and 25 last overview of developments in field published Journal Biological Rhythms. Here, we explore new mechanisms concepts that have emerged subsequent years. Since 1997, methodological developments, such luminescent fluorescent reporter techniques, revealed intricate relationships between cellular network-level mechanisms. In particular, specific neuropeptides arginine vasopressin, vasoactive intestinal peptide, gastrin-releasing peptide key players synchronization rhythms within SCN. The discovery multiple oscillators governing behavioral physiological significantly advanced our understanding clock. interaction neurons glial cells found to play a crucial role regulating these Furthermore, properties SCN network vary across ontogenetic stages. application cell type–specific genetic manipulations components functional input-output system their correlation with functions. This review concludes high-risk effort identifying open questions challenges lie ahead.

Language: Английский

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Circadian Rhythms and Astrocytes: The Good, the Bad, and the Ugly

Annual Review of Neuroscience, Journal Year: 2023, Volume and Issue: 46(1), P. 123 - 143

Published: Feb. 28, 2023

This review explores the interface between circadian timekeeping and regulation of brain function by astrocytes. Although astrocytes regulate neuronal activity across many time domains, their cell-autonomous clocks exert a particular role in controlling longer-term oscillations function: maintenance sleep states ordering wakefulness. is most evident central pacemaker, suprachiasmatic nucleus, where molecular clock suffices to drive daily cycles behavior. In Alzheimer's disease, impairments accompany cognitive decline. mouse models disturbances accelerate astroglial activation other pathologies, suggesting that functions protect homeostasis. cancer, treatment morning has been associated with prolonged survival, gliomas have rhythms gene expression drug sensitivity. Thus, fast becoming critical elucidating reciprocal astrocytic-neuronal interactions health disease.

Language: Английский

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The Mammalian Circadian Time-Keeping System

Journal of Huntington s Disease, Journal Year: 2023, Volume and Issue: 12(2), P. 91 - 104

Published: April 25, 2023

Our physiology and behavior follow precise daily programs that adapt us to the alternating opportunities challenges of day night. Under experimental isolation, these rhythms persist with a period approximately one (circadian), demonstrating their control by an internal autonomous clock. Circadian time is created at cellular level transcriptional/translational feedback loop (TTFL) in which protein products Period Cryptochrome genes inhibit own transcription. Because accumulation slow delayed, system oscillates spontaneously ∼24 hours. This cell-autonomous TTFL controls cycles gene expression all major tissues underpin our metabolic programs. In turn, innumerable clocks are coordinated central pacemaker, suprachiasmatic nucleus (SCN) hypothalamus. When isolated slice culture, SCN its dependent neural activity indefinitely, operating as "a clock dish". vivo, synchronized solar direct innervation from specialized retinal photoreceptors. circadian cycle action potential firing signals SCN-generated hypothalamic brain stem targets, co-ordinate downstream autonomic, endocrine, behavioral (feeding) cues synchronize sustain distributed network. therefore pervades every biological organization, molecules society. Understanding mechanisms offers important mitigate consequences disruption, so prevalent modern societies, arise shiftwork, aging, neurodegenerative diseases, not least Huntington's disease.

Language: Английский

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Astrocytic modulation of neuronal signalling

Frontiers in Network Physiology, Journal Year: 2023, Volume and Issue: 3

Published: June 1, 2023

Neuronal signalling is a key element in neuronal communication and essential for the proper functioning of CNS. Astrocytes, most prominent glia brain play role modulating at molecular, synaptic, cellular, network levels. Over past few decades, our knowledge about astrocytes their has evolved from considering them as merely glue that provides structural support to neurons, elements. Astrocytes can regulate activity neurons by controlling concentrations ions neurotransmitters extracellular milieu, well releasing chemicals gliotransmitters modulate activity. The aim this review summarise main processes through which are function. We will systematically distinguish between direct indirect pathways affect all Lastly, we summarize pathological conditions arise once these impaired focusing on neurodegeneration.

Language: Английский

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Astrocytic control of extracellular GABA drives circadian timekeeping in the suprachiasmatic nucleus

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(21)

Published: May 15, 2023

The hypothalamic suprachiasmatic nucleus (SCN) is the master mammalian circadian clock. Its cell-autonomous timing mechanism, a transcriptional/translational feedback loop (TTFL), drives daily peaks of neuronal electrical activity, which in turn control behavior. Intercellular signals, mediated by neuropeptides, synchronize and amplify TTFL rhythms across circuit. SCN neurons are GABAergic, but role GABA circuit-level timekeeping unclear. How can GABAergic circuit sustain cycles when such increased firing should become inhibitory to network? To explore this paradox, we show that slices expressing sensor iGABASnFR demonstrate oscillation extracellular ([GABA]

Language: Английский

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Glymphatic and lymphatic communication with systemic responses during physiological and pathological conditions in the central nervous system

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: Feb. 24, 2024

Abstract Crosstalk between central nervous system (CNS) and systemic responses is important in many pathological conditions, including stroke, neurodegeneration, schizophrenia, epilepsy, etc. Accumulating evidence suggest that signals for central-systemic crosstalk may utilize glymphatic lymphatic pathways. The functionally connected to the meningeal system, together these pathways be involved distribution of soluble proteins clearance metabolites waste products from CNS. Lymphatic vessels dura meninges transport cerebrospinal fluid, part collected cervical lymph nodes, where solutes coming brain (i.e., VEGFC, oligomeric α-syn, β-amyloid) might activate a inflammatory response. There also an element time since immune strongly regulated by circadian rhythms, both dynamics have been shown change during day night. Understanding mechanisms regulating brain-cervical node (CLN) signaling how it affected diurnal or rhythms fundamental find specific targets timing therapeutic interventions.

Language: Английский

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Prefrontal cortex astroglia modulate anhedonia-like behavior

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(11), P. 4632 - 4641

Published: Sept. 11, 2023

Abstract Reductions of astroglia expressing glial fibrillary acidic protein (GFAP) are consistently found in the prefrontal cortex (PFC) patients with depression and rodent chronic stress models. Here, we examine consequences PFC GFAP+ cell depletion activity enhancement on depressive-like behaviors rodents. Using viral expression diphtheria toxin receptor cells, which allows experimental these cells following administration, demonstrated that induced anhedonia-like behavior within 2 days lasting up to 8 days, but no anxiety-like deficits. Conversely, activating for 3 weeks using designer exclusively activated by drugs (DREADDs) reversed restraint stress-induced deficits, not Our results highlight a critical role cortical development anhedonia further support idea targeting treatment depression.

Language: Английский

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

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

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Estrogen‐mediated coupling via gap junctions in the suprachiasmatic nucleus

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

Published: Feb. 7, 2024

Abstract The circadian clock orchestrates many physiological and behavioural rhythms in mammals with 24‐h periodicity, through a hierarchical organisation, the central located suprachiasmatic nucleus (SCN) hypothalamus. circuits of SCN generate precision, relying on intrinsic coupling mechanisms, for example, neurotransmitters like arginine vasopressin (AVP), vasoactive intestinal peptide (VIP), neuronal gamma‐aminobutyric acid (GABA) signalling astrocytes connected by gap junctions composed connexins (Cx). In female rodents, presence estrogen receptors (ERs) dorsal suggests an influence (E2) circuit timekeeping that could regulate rhythm coupling. To investigate this, we used explants together hypothalamic neurons astrocytes. First, showed E2 stabilised amplitude when rAVPs (receptor‐associated peptides) were inhibited. However, phase delay induced VIPAC2 (VIP receptors) inhibition remained unaffected E2. We then exerted its effects via ERβ (estrogen receptor beta), resulting increased expression Cx36 Cx43 . Notably, specific both resulted significant reduction within SCN. Remarkably, restored period inhibited but not inhibition. This implies network between neurons, responsible SCN, can be reinforced conclusion, these findings provide new insights into how regulates ex vivo ERβ‐dependent manner, underscoring crucial role fortifying SCN's rhythm.

Language: Английский

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BMAL1 in Astrocytes: A Protective Role in Alzheimer’s and Parkinson’s Disease

Neuroglia, Journal Year: 2025, Volume and Issue: 6(1), P. 1 - 1

Published: Jan. 2, 2025

Astrocyte activation is a critical aspect of brain health and disease, the central circadian clock protein BMAL1 has emerged as regulator astrogliosis inflammatory gene expression. Bmal1 deletion in astrocytes reprograms endolysosomal transcriptional pathways, inducing endocytosis, lysosomal degradation, autophagic activity. This regulation proteostasis by implicates proteins neurodegenerative diseases. Studies suggest that astrocyte complex process with diverse phenotypes beyond classic markers such GFAP, exhibiting neurotoxic neuroprotective effects. Deletion shown protective effects models Alzheimer’s disease (AD) Parkinson’s (PD), influencing Aβ accumulation α-syn pathology, respectively, through state mitigates tauopathy possibly induction chaperone BAG3. These findings crucial regulating astrocytic function neuroprotection review explores relationship between dysfunction development/progression AD PD. Furthermore, it recapitulates most recent on manipulating its potential astrocytes.

Language: Английский

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