Invited Review: A neural clockwork for encoding circadian time

2002 ◽  
Vol 92 (1) ◽  
pp. 401-408 ◽  
Author(s):  
Erik D. Herzog ◽  
William J. Schwartz
Keyword(s):  
Nervous System ◽  
Single Cell ◽  
Suprachiasmatic Nucleus ◽  
Biological Rhythms ◽  
Anterior Hypothalamus ◽  
Circadian Clocks ◽  
Circadian Pacemaker ◽  
Environmental Light ◽  
Circadian Time ◽  
Oscillatory Mechanism

10.1152/japplphysiol.00836.2001.—Many daily biological rhythms are governed by an innate timekeeping mechanism or clock. Endogenous, temperature-compensated circadian clocks have been localized to discrete sites within the nervous systems of a number of organisms. In mammals, the master circadian pacemaker is the bilaterally paired suprachiasmatic nucleus (SCN) in the anterior hypothalamus. The SCN is composed of multiple single cell oscillators that must synchronize to each other and the environmental light schedule. Other tissues, including those outside the nervous system, have also been shown to express autonomous circadian periodicities. This review examines 1) how intracellular regulatory molecules function in the oscillatory mechanism and in its entrainment to environmental cycles; 2) how individual SCN cells interact to create an integrated tissue pacemaker with coherent metabolic, electrical, and secretory rhythms; and 3) how such clock outputs are converted into temporal programs for the whole organism.

4. Shedding light on the clock

2017 ◽  
pp. 45-61
Author(s):  
Russell G. Foster ◽  
Leon Kreitzman
Keyword(s):  
Nervous System ◽  
Autonomic Nervous System ◽  
Physical Exercise ◽  
Circadian Clock ◽  
Suprachiasmatic Nucleus ◽  
Human Body ◽  
Circadian Clocks ◽  
Autonomic Nervous ◽  
Over Time ◽  
Daily Patterns

Most circadian clocks make use of a sun-based mechanism as the primary entraining signal to lock the internal day to the astronomical day. For nearly four billion years, dawn and dusk has been the main zeitgeber that allows entrainment. Circadian clocks are not exactly 24 hours. So to prevent daily patterns of activity and rest from freerunning over time, light can reset the clock. ‘Shedding light on the clock’ explains that the main circadian clock has been located in the suprachiasmatic nucleus in the hypothalamus. This also regulates the activity of the autonomic nervous system, but there are clocks in virtually every cell in the human body. Other zeitgebers include food, physical exercise, and temperature.

scholarly journals The suprachiasmatic nucleus: age-related decline in biological rhythms

2016 ◽  
Vol 66 (5) ◽  
pp. 367-374 ◽  
Author(s):  
Takahiro J. Nakamura ◽  
Nana N. Takasu ◽  
Wataru Nakamura
Keyword(s):  
Suprachiasmatic Nucleus ◽  
Biological Rhythms ◽  
Age Related

Effect of somatostatin on circadian rhythms of firing and 2-deoxyglucose uptake in rat suprachiasmatic slices

1993 ◽  
Vol 265 (5) ◽  
pp. R1199-R1204 ◽  
Author(s):  
T. Hamada ◽  
S. Shibata ◽  
A. Tsuneyoshi ◽  
K. Tominaga ◽  
S. Watanabe
Keyword(s):  
Circadian Rhythm ◽  
Vasoactive Intestinal Polypeptide ◽  
Phase Changes ◽  
Circadian Clocks ◽  
Constant Darkness ◽  
Phase Resetting ◽  
Firing Activity ◽  
Light Pulses ◽  
Circadian Time

In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus appears to act as a circadian clock. The SCN vasoactive intestinal polypeptide-like immunoreactive neurons, which may act to mediate photic information in the SCN, receive input from neurons immunoreactive for somatostatin (SST). Therefore we investigated the role of SST as a transmitter for entrainment by analyzing the phase-resetting effect of SST on the circadian rhythm of SCN firing activity. Perfusion of SST increased 2-deoxyglucose uptake at circadian time (CT) 18, but not at CT6. A 1-h or 15-min treatment with SST produced phase delays when it was administered at CT13-14 and phase advances at CT22-23. Thus SST-induced phase changes are similar to those for light pulses to animals under constant darkness. The present findings suggest that SST is a transmitter for mediating information of entrainment to circadian clocks within the SCN.

scholarly journals Single cell transcriptomic analysis of diffuse large B cells in cerebrospinal fluid of central nervous system lymphoma

2020 ◽  
Author(s):  
Haoyu Ruan ◽  
Zhe Wang ◽  
Yue Zhai ◽  
Ying Xu ◽  
Linyu Pi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
B Cells ◽  
B Cell ◽  
Single Cell ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Great Promise ◽  
Leptomeningeal Involvement

AbstractDiffuse large B-cell lymphoma (DLBCL) is the predominant type of central nervous system lymphoma (CNSL) including primary CNSL and secondary CNSL. Diffuse large B cells in cerebrospinal fluid (CSF-DLBCs) have offered great promise for the diagnostics and therapeutics of CNSL leptomeningeal involvement. To explore the distinct phenotypic states of CSF-DLBCs, we analyzed the transcriptomes of 902 CSF-DLBCs from six CNSL-DLBCL patients using single-cell RNA sequencing technology. We defined CSF-DLBCs based on abundant expression of B-cell markers, as well as the enrichment of cell proliferation and energy metabolism pathways. CSF-DLBCs within individual patients exhibited monoclonality with similar variable region of light chains (VL) expression. It is noteworthy that we observed some CSF-DLBCs have double classes of VL (lambda and kappa) transcripts. We identified substantial heterogeneity in CSF-DLBCs, and found significantly greater among-patient heterogeneity compared to among-cell heterogeneity within a given patient. The transcriptional heterogeneity across CSF-DLBCs is manifested in cell cycle state and cancer-testis antigens expression. Our results will provide insight into the mechanism research and new diagnostic direction of CNSL-DLBCL leptomeningeal involvement.

scholarly journals Single-cell immune repertoire and transcriptome sequencing reveals that clonally expanded and transcriptionally distinct lymphocytes populate the aged central nervous system in mice

2021 ◽  
Vol 288 (1945) ◽  
pp. 20202793
Author(s):  
Alexander Yermanos ◽  
Daniel Neumeier ◽  
Ioana Sandu ◽  
Mariana Borsa ◽  
Ann Cathrin Waindok ◽  
...  
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Nervous System ◽  
B Cells ◽  
Single Cell ◽  
Somatic Hypermutation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cell Receptor ◽  
The Central Nervous System

Neuroinflammation plays a crucial role during ageing and various neurological conditions, including Alzheimer's disease, multiple sclerosis and infection. Technical limitations, however, have prevented an integrative analysis of how lymphocyte immune receptor repertoires and their accompanying transcriptional states change with age in the central nervous system. Here, we leveraged single-cell sequencing to simultaneously profile B cell receptor and T cell receptor repertoires and accompanying gene expression profiles in young and old mouse brains. We observed the presence of clonally expanded B and T cells in the central nervous system of aged male mice. Furthermore, many of these B cells were of the IgM and IgD isotypes, and had low levels of somatic hypermutation. Integrating gene expression information additionally revealed distinct transcriptional profiles of these clonally expanded lymphocytes. Our findings implicate that clonally related T and B cells in the CNS of elderly mice may contribute to neuroinflammation accompanying homeostatic ageing.

scholarly journals Microglia response following acute demyelination is heterogeneous and limits infiltrating macrophage dispersion

2020 ◽  
Vol 6 (3) ◽  
pp. eaay6324 ◽  
Author(s):  
Jason R. Plemel ◽  
Jo Anne Stratton ◽  
Nathan J. Michaels ◽  
Khalil S. Rawji ◽  
Eric Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Sciatic Nerve ◽  
Single Cell ◽  
Peripheral Inflammation ◽  
Macrophage Response ◽  
Single Cell Rna Sequencing ◽  
Privileged Status ◽  
The Central Nervous System

Microglia and infiltrating macrophages are thought to orchestrate the central nervous system (CNS) response to injury; however, the similarities between these cells make it challenging to distinguish their relative contributions. We genetically labeled microglia and CNS-associated macrophages to distinguish them from infiltrating macrophages. Using single-cell RNA sequencing, we describe multiple microglia activation states, one of which was enriched for interferon associated signaling. Although blood-derived macrophages acutely infiltrated the demyelinated lesion, microglia progressively monopolized the lesion environment where they surrounded infiltrating macrophages. In the microglia-devoid sciatic nerve, the infiltrating macrophage response was sustained. In the CNS, the preferential proliferation of microglia and sparse microglia death contributed to microglia dominating the lesion. Microglia ablation reversed the spatial restriction of macrophages with the demyelinated spinal cord, highlighting an unrealized macrophages-microglia interaction. The restriction of peripheral inflammation by microglia may be a previously unidentified mechanism by which the CNS maintains its “immune privileged” status.

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