Melatonin Enters the Cerebrospinal Fluid through the Pineal Recess

Tricoire, H.; Locatelli, A.; Chemineau, Philippe; Malpaux, Benoît

doi:10.1210/endo.143.1.8585

Cited by 153 publications

(51 citation statements)

References 21 publications

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“…Interestingly, Mel concentration is 20 times higher in the third ventricle CSF than in plasma 53. Tricoire et al 54. further showed that Mel is released into the pineal recess (a third ventricle evagination penetrating into the pineal gland) and is then distributed throughout the ventricular system to possibly reach the periventricular binding sites.…”

Section: Discussionmentioning

confidence: 99%

Altered interactions of tryptophan metabolites in first-episode neuroleptic-naive patients with schizophrenia

et al. 2009

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Schizophrenia is characterized by complex and dynamically interacting perturbations in multiple neurochemical systems. In the past, evidence for these alterations has been collected piecemeal, limiting our understanding of the interactions among relevant biological systems. Earlier, both hyper-and hyposerotonemia were variously associated with the longitudinal course of schizophrenia, suggesting a disturbance in the central serotonin (5-hydroxytryptamine (5-HT)) function. Using a targeted electrochemistry-based metabolomics platform, we compared metabolic signatures consisting of 13 plasma tryptophan (Trp) metabolites simultaneously between first-episode neuroleptic-naive patients with schizophrenia (FENNS, n = 25) and healthy controls (HC, n = 30). We also compared these metabolites between FENNS at baseline (BL) and 4 weeks (4w) after antipsychotic treatment. N-acetylserotonin was increased in FENNS-BL compared with HC (P = 0.0077, which remained nearly significant after Bonferroni correction). N-acetylserotonin/Trp and melatonin (Mel)/serotonin ratios were higher, and Mel/N-acetylserotonin ratio was lower in FENNS-BL (all P-values < 0.0029), but not after treatment, compared with HC volunteers. All three groups had highly significant correlations between Trp and its metabolites, Mel, kynurenine, 3-hydroxykynurenine and tryptamine. However, in the HC, but in neither of the FENNS groups, serotonin was highly correlated with Trp, Mel, kynurenine or tryptamine, and 5-hydroxyindoleacetic acid (5HIAA) was highly correlated with Trp, Mel, kynurenine or 3-hydroxykynurenine. A significant difference between HC and FENNS-BL was further shown only for the Trp-5HIAA correlation. Thus, some metabolite interactions within the Trp pathway seem to be altered in the FENNS-BL patients. Conversion of serotonin to N-acetylserotonin by serotonin N-acetyltransferase may be upregulated in FENNS patients, possibly related to the observed alteration in Trp-5HIAA correlation. Considering N-acetylserotonin as a potent antioxidant, such increases in N-acetylserotonin might be a compensatory response to increased oxidative stress, implicated in the pathogenesis of schizophrenia. Molecular Psychiatry (2010) 15, 938-953;

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Section: Discussionmentioning

confidence: 99%

Altered interactions of tryptophan metabolites in first-episode neuroleptic-naive patients with schizophrenia

et al. 2009

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“…The hormone is transferred by CSF to the SCN, other hypothalamic regions, the hippocampus, and choroid plexuses, where there are high affinity MT1 receptors [56]. Lateral ventricle (LV) melatonin concentrations have been reported to be far lower than 3V melatonin concentrations; this observation has been used in part to argue that 3V melatonin is not coming from recirculation via the plasma and choroid plexuses but rather through direct secretion into the pineal recess [159,183]. Indeed, in sheep, brain melatonin concentration close to the third ventricle walls and aqueduct of Sylvius is double that of plasma [110], penetrating 8-10 mm into brain as the concentration gradually falls.…”

Section: The Need For Csf-brain Isf Exchangementioning

confidence: 99%

The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system?

et al. 2018

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Brain fluids are rigidly regulated to provide stable environments for neuronal function, e.g., low K + , Ca 2+ , and protein to optimise signalling and minimise neurotoxicity. At the same time, neuronal and astroglial waste must be promptly removed. The interstitial fluid (ISF) of the brain tissue and the cerebrospinal fluid (CSF) bathing the CNS are integral to this homeostasis and the idea of a glia-lymph or 'glymphatic' system for waste clearance from brain has developed over the last 5 years. This links bulk (convective) flow of CSF into brain along the outside of penetrating arteries, glia-mediated convective transport of fluid and solutes through the brain extracellular space (ECS) involving the aquaporin-4 (AQP4) water channel, and finally delivery of fluid to venules for clearance along peri-venous spaces. However, recent evidence favours important amendments to the 'glymphatic' hypothesis, particularly concerning the role of glia and transfer of solutes within the ECS. This review discusses studies which question the role of AQP4 in ISF flow and the lack of evidence for its ability to transport solutes; summarizes attributes of brain ECS that strongly favour the diffusion of small and large molecules without ISF flow; discusses work on hydraulic conductivity and the nature of the extracellular matrix which may impede fluid movement; and reconsiders the roles of the perivascular space (PVS) in CSF-ISF exchange and drainage. We also consider the extent to which CSF-ISF exchange is possible and desirable, the impact of neuropathology on fluid drainage, and why using CSF as a proxy measure of brain components or drug delivery is problematic. We propose that new work and key historical studies both support the concept of a perivascular fluid system, whereby CSF enters the brain via PVS convective flow or dispersion along larger caliber arteries/arterioles, diffusion predominantly regulates CSF/ISF exchange at the level of the neurovascular unit associated with CNS microvessels, and, finally, a mixture of CSF/ISF/waste products is normally cleared along the PVS of venules/veins as well as other pathways; such a system may or may not constitute a true 'circulation', but, at the least, suggests a comprehensive re-evaluation of the previously proposed 'glymphatic' concepts in favour of a new system better taking into account basic cerebrovascular physiology and fluid transport considerations.

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“…In addition to this role in daily rhythms, the melatonin signal is essential for the integration of seasonal photoperiodic changes in physiology [6], thereby determining the best time for reproduction and associated physiological and behavioural changes to occur [7].…”

Section: Introductionmentioning

confidence: 99%

Proteomic analysis of day–night variations in protein levels in the rat pineal gland

et al. 2007

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The pineal gland secretes the hormone melatonin. This secretion exhibits a circadian rhythm with a zenith during night and a nadir during day. We have performed proteome analysis of the superficial pineal gland in rats during daytime and nighttime. The proteins were extracted and subjected to 2-DE. Of 1747 protein spots revealed by electrophoresis, densitometric analysis showed the up-regulation of 25 proteins during nighttime and of 35 proteins during daytime. Thirty-seven of the proteins were identified by MALDI-TOF MS. The proteins up-regulated during the night are involved in the Krebs cycle, energy transduction, calcium binding, and intracellular transport. During the daytime, enzymes involved in glycolysis, electron transport, and also the Krebs cycle were up-regulated as well as proteins taking part in RNA binding and RNA processing. Our data show a prominent day-night variation of the protein levels in the rat pineal gland. Some proteins are up-regulated during the night concomitant with the melatonin secretion of the gland. Other proteins are up-regulated during the day indicating a pineal metabolism not related to the melatonin synthesis.

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Melatonin Enters the Cerebrospinal Fluid through the Pineal Recess

Cited by 153 publications

References 21 publications

Altered interactions of tryptophan metabolites in first-episode neuroleptic-naive patients with schizophrenia

Altered interactions of tryptophan metabolites in first-episode neuroleptic-naive patients with schizophrenia

The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system?

Proteomic analysis of day–night variations in protein levels in the rat pineal gland

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