Modulation of immunoactive levels of DSIP and blood‐brain barrier permeability by lighting and diurnal rhythm

Banks, William A.; Kastin, Abba J.; Selznick, J. K.

doi:10.1002/jnr.490140307

Cited by 31 publications

(9 citation statements)

References 22 publications

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“…The release of cytokines by different cells, as well as their recirculation within the CNS, is thought to be regulated by circadian rhythm. Circadian control of BBB permeability, CSF production, and cellular cytokine release are all suggestive of a precise spatiotemporal mechanism that controls cytokine levels in the brain and also affects neuronal activity (Agorastos et al, 2014; Banks et al, 1985; Entzian et al, 1996; Keller et al, 2009; Nilsson et al, 1992).…”

Section: Meningeal Lymphatics−glymphatics and Neuromodulation By Cytomentioning

confidence: 99%

The Meningeal Lymphatic System: A New Player in Neurophysiology

Mesquita

Kipnis

2018

Neuron

352

274

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Summary The nature of fluid dynamics within the brain parenchyma is a focus of intensive research. Of particular relevance is its participation in diseases associated with protein accumulation and aggregation in the brain, such as Alzheimer’s disease (AD). The meningeal lymphatic vessels of the central nervous system have recently been recognized as an important player in the complex circulation and exchange of soluble contents between the cerebrospinal fluid (CSF) and the interstitial fluid (ISF). In aging mammals, for example, impaired functioning of the meningeal lymphatic vessels can lead to accelerated accumulation of toxic amyloid beta protein in the brain parenchyma, thus aggravating AD-related pathology. Given that meningeal lymphatic vessels are functionally linked to paravascular influx/efflux of the CSF/ISF, and in light of recent findings that certain cytokines, classically perceived as immune molecules, exert neuromodulatory effects, it is reasonable to suggest that the activity of meningeal lymphatics could alter the accessibility of CSF-borne immune neuromodulators to the brain parenchyma, thereby altering their effects on the brain. Accordingly, in this Perspective we discuss the suggestion that the meningeal lymphatic system can be viewed as a novel player in neurophysiology.

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Section: Meningeal Lymphatics−glymphatics and Neuromodulation By Cytomentioning

confidence: 99%

The Meningeal Lymphatic System: A New Player in Neurophysiology

Mesquita

Kipnis

2018

Neuron

352

274

View full text Add to dashboard Cite

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“…The concentrations of several molecules in the CNS undergo circadian oscillations, likely because of their rhythmic entry into the CNS (Table 1). These include tumor necrosis factor alpha (TNFα) [21], leptin [22], β-amyloid [23], delta-sleep inducing peptide (DSIP) [24], and prostaglandin D2 (PGD2) [25]. When TNFα, an inflammatory cytokine, was intravenously injected into mice with an iodine label ( 125 I-TNFα), uptake into the spinal cord demonstrated a circadian rhythm [21], such that greatest TNFα uptake occurred between Zeitgeber time (ZT) 20-ZT23 (ZT0, lights on; ZT12, lights off); interestingly the same rhythmic uptake did not occur in the brain [21].…”

Section: Rhythmic Expression Of Several Secreted Molecules In the Brainmentioning

confidence: 99%

Regulation of the Blood–Brain Barrier by Circadian Rhythms and Sleep

Cuddapah

Zhang

Sehgal

2019

Trends in Neurosciences

147

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The blood-brain barrier (BBB) is an evolutionarily conserved, structural, and functional separation between circulating blood and the central nervous system (CNS). By controlling permeability into and out of the nervous system, the BBB has a critical role in the precise regulation of neural processes. Here, we review recent studies demonstrating that permeability at the BBB is dynamically controlled by circadian rhythms and sleep. An endogenous circadian rhythm in the BBB controls transporter function, regulating permeability across the BBB. In addition, sleep promotes the clearance of metabolites along the BBB, as well as endocytosis across the BBB. Finally, we highlight the implications of this regulation for diseases, including epilepsy. The Blood-Brain Barrier Is a Dynamic StructureA growing body of evidence demonstrates that the blood-brain barrier (BBB) is not a static structure, but instead is a site of active regulation. As a cellular structure that separates circulatory fluids (e.g., blood and hemolymph) from the brain, the BBB imposes strict regulation on molecules moving into and out of the central nervous system (CNS). Here, we focus on recent studies demonstrating that both circadian rhythms and sleep regulate the movement of molecules across and along the BBB.Circadian rhythms are biological processes that endogenously oscillate with a period of~24 h. This rhythm is driven by a molecular clock and can be synchronized with, but is not reliant upon, external cues (e.g., light, temperature, and feeding patterns). While the central circadian pacemaker is in the brain (e.g., the suprachiasmatic nucleus in mammals), other cells, including the cells of the BBB [1,2], have autonomous circadian rhythms driven by molecular clocks [3]. In addition, the large arteries that perfuse the brain in mammals themselves contain endogenous circadian clocks [4,5]. Critical studies originating in Drosophila melanogaster and then extended to mammals revealed that molecular clocks comprise transcriptional feedback loops. The core of this auto-regulatory loop in Drosophila involves the proteins Period (PER) and Timeless (TIM) inhibiting their own transcription at a specific time of day by acting on the transcriptional activators Clock (CLK) and Cycle (CYC) [6]. HighlightsRecent evidence from fly models reveals an endogenous circadian rhythm at the BBB. This rhythm controls function of the permeability-glycoprotein multidrug transporter, which actively pumps both endogenous and exogenous molecules out of the CNS. Function of this transporter is decreased at night, increasing permeability to multiple substrates into the brain overnight.Endocytosis is a newly appreciated important function for sleep. Endocytosis across the BBB is increased during sleep and, when inhibited, increases the need for sleep.Sleep also promotes the clearance of metabolites out of the brain along paravascular spaces. During sleep, the interstitial spaces of the brain are larger, allowing for more robust movement of metabolites from interstitial spaces ...

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“…Mathematical modeling and computer simulation techniques for understanding the total regulatory system of sleep mechanisms. 4. Techniques for the analysis of ultradian, circadian and infradian rhythms of locomotor activity, body temperature and behavioral state in animals.…”

Section: Continuous Systemic Intracerebroventricular (Icv) or Intracmentioning

confidence: 99%