Signaling within the pineal gland: A parallelism with the central nervous system

Altamirano, Luz E. Farias; Freites, Carlos Leandro; Vásquez, Elena; Muñoz, Estela M.

doi:10.1016/j.semcdb.2018.11.004

Cited by 6 publications

(13 citation statements)

References 118 publications

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“…The pineal gland (PG) is an unpaired organ located in the roof of the diencephalon, associated with the third ventricle ( Kiecker, 2018 ; Moller and Baeres, 2002 ). This secretory CVO is the primary source of melatonin (MEL), which is a time-cue hormone that is conserved across species, including humans ( Arendt, 2003 ; Farias Altamirano et al, 2019 ; Maronde and Stehle, 2007 ). The PG synthesizes MEL in its main cell type, the pinealocytes, and releases it into the blood and CSF at night, which synchronizes physiology and behavior to the prevailing environmental light-dark conditions ( Lee et al, 2020 ; Mays et al, 2018 ; Simonneaux and Ribelayga, 2003 ; Tan et al, 2016 ; Yu et al, 2016 ).…”

Section: Pineal Gland: a Secretory Circumventricular Organmentioning

confidence: 99%

Microglia in Circumventricular Organs: The Pineal Gland Example

Muñoz

2022

ASN Neuro

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The circumventricular organs (CVOs) are unique areas within the central nervous system. They serve as a portal for the rest of the body and, as such, lack a blood-brain barrier. Microglia are the primary resident immune cells of the brain parenchyma. Within the CVOs, microglial cells find themselves continuously challenged and stimulated by local and systemic stimuli, even under steady-state conditions. Therefore, CVO microglia in their typical state often resemble the activated microglial forms found elsewhere in the brain as they are responding to pathological conditions or other stressors. In this review, I focus on the dynamics of CVO microglia, using the pineal gland as a specific CVO example. Data related to microglia heterogeneity in both homeostatic and unhealthy environments are presented and discussed, including those recently generated by using advanced single-cell and single-nucleus technology. Finally, perspectives in the CVO microglia field are also included. Summary Statement Microglia in circumventricular organs (CVOs) continuously adapt to react differentially to the diverse challenges they face. Herein, I discuss microglia heterogeneity in CVOs, including pineal gland. Further studies are needed to better understand microglia dynamics in these unique brain areas.

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Section: Pineal Gland: a Secretory Circumventricular Organmentioning

confidence: 99%

Microglia in Circumventricular Organs: The Pineal Gland Example

Muñoz

2022

ASN Neuro

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“…Melatonin (MEL), N ‐acetyl‐5‐methoxytryptamine, is a hormone synthesized and secreted mainly by the pineal gland 10,11 . It is released overnight following a circadian cycle and functions as a biological synchronizer.…”

Section: Introductionmentioning

confidence: 99%

“…Melatonin (MEL), N-acetyl-5-methoxytryptamine, is a hormone synthesized and secreted mainly by the pineal gland. 10,11 It is released overnight following a circadian cycle and functions as a biological synchronizer. Remarkably, MEL is also produced in various organs where MEL-synthesizing enzymes are found: retina, ovaries, gastrointestinal tract, immune system, salivary glands, and gingiva.…”

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confidence: 99%

Melatonin protects gingival mesenchymal stem cells and promotes differentiation into osteoblasts

Solá

Aguilar

Farías³

et al. 2022

Cell Biochemistry & Function

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Melatonin (MEL) has antioxidant properties and participates in osteogenic differentiation. In periodontitis, in which increased oxidative stress and bone resorption are involved, mesenchymal stem cells derived from the gingiva (GMSCs) combined with MEL could be relevant for osteogenic regeneration. In this study, we studied the antioxidant and differentiating effect of MEL on an in vitro system of GMSCs. Primary culture of GMSCs from Wistar rats was developed to evaluate differentiation into osteoblasts with an appropriate medium with or without MEL. Marker genes of mesenchymal stem cells by real time‐polymerase chain reaction, clonogenic capacity, and cell migration after wound assay were used to characterize GMSCs as mesenchymal stem cells. Alkaline phosphatase activity and the alizarin red technique were used to evaluate osteogenic activity and differentiation. MEL increased alkaline phosphatase activity and alizarin red values, promoting osteogenic differentiation. Besides this, MEL protected GMSCs in a model of cellular damage related to oxidative stress, returning viability to baseline. MEL was more effective in promoting and protecting GMSCs by the production of osteogenic cells when oxidative stress is present. This evidence supports the use of MEL as a novel bone‐regenerative therapy in periodontal diseases.

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“…In rat, the multisynaptic circadian timing system (CTS) exerts its control over the PG via nighttime release of norepinephrine (NE) from sympathetic nerve endings stemming from neurons located in the superior cervical ganglia (SCG) (1,2,4). NE binds to β1 and α1 adrenergic receptors on the pinealocyte membrane, which triggers cooperative signaling cascades that end with the transient cAMP-induced phosphorylation of nuclear CREB1 at the Ser 133 residue (pSer 133 -CREB1), as well as other related processes (4,7,8,12,22,23).…”

Section: Introductionmentioning

confidence: 99%

“…In vertebrates, the pineal gland (PG) is part of a multicentric circuit that imposes circadian rhythmicity to physiology and behavior (1, 2). Nowadays, it is widely accepted that melatonin, produced by pinealocytes at night, serves as the indole hormone responsible for disseminating this chronobiological cue (3).…”

Section: Introductionmentioning

confidence: 99%

Spatio-temporal dynamics of nuclear CREB1: what does it mean?

Altamirano

Vásquez

Freites

et al. 2022

Preprint

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In the mammalian pineal gland (PG), cyclic AMP responsive element-binding protein 1 (CREB1) participates in the nocturnal melatonin synthesis that rhythmically modulates physiology and behavior. Phosphorylation of CREB1 present in pinealocyte nuclei is one of the key regulatory steps that drives pineal transcription. The spatio-temporal dynamics of CREB1 itself within PG cell types have not yet been documented. In this study we analyzed total CREB1 via Western blot, and the dynamism of CREB1 nuclear distribution in individual rat pinealocytes using fluorescence immunohistochemistry followed by confocal laser-scanning microscopy and quantitative analysis. Total CREB1 levels remained constant in the PG throughout the light:dark cycle. The distribution pattern of nuclear CREB1 did vary, however, among different PG cells. Pinealocytes emerged as having discrete CREB1 domains within their nucleoplasm that were especially distinct. The number, size, and location of CREB1 foci fluctuated among pinealocytes, within the same PG and among Zeitgeber times. A significantly larger dispersion of CREB1-immunoreactive nuclear sites was found at night. This was not accompanied by changes in the overall transcription activity, which was mostly conserved between the light and dark phases, as shown by the expression of a particular phosphorylated form of the RNA polymerase II (RNAPII-pSer5CTD). Suppression of the nocturnal norepinephrine pulse by chronic bilateral superior cervical ganglionectomy increased CREB1 dispersion in pinealocyte nuclei, as compared to sham-derived cells. In addition, differences in CREB1 distribution were found between sham-operated and non-operated rats at early night. Together, these data suggest that in mature pinealocytes nuclear CREB1 is subjected to a dynamic spatio-temporal distribution. Further studies are necessary to elucidate the underlying mechanisms, including the role of chromatin and interchromatin elements, and to understand the impact of CREB1 reorganization in the pineal transcriptome.

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Signaling within the pineal gland: A parallelism with the central nervous system

Cited by 6 publications

References 118 publications

Microglia in Circumventricular Organs: The Pineal Gland Example

Microglia in Circumventricular Organs: The Pineal Gland Example

Melatonin protects gingival mesenchymal stem cells and promotes differentiation into osteoblasts

Spatio-temporal dynamics of nuclear CREB1: what does it mean?

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