<scp>GABA</scp>ergic signaling in the rat pineal gland

Hou, Yu; Benitez, Sergio Gonzalo; Jung, Seung Ryoung; Altamirano, Luz E. Farias; Kruse, Martin; Seo, Jong Bae; Koh, Duk Su; Muñoz, Estela M.; Hille, Bertil

doi:10.1111/jpi.12328

Cited by 14 publications

(10 citation statements)

References 53 publications

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“…Our data show that all dividing cells expressed Pax6 during this same developmental window, indicating that Pax6+ precursor cells produce the pinealocyte lineage. We also noted that Pax6-expressing cells were still present in the adult gland, distributed evenly across the organ (Figs 2C 1 –2C 4 and 3E 1 –3E 3 ) [42]. Many of the Pax6+ cells in the adult pineal gland also expressed detectable levels of vimentin (Fig 3E 1 –3E 3 ), suggesting the possibility that they may also generate astroglial cells.…”

Section: Resultsmentioning

confidence: 83%

Cellular Basis of Pineal Gland Development: Emerging Role of Microglia as Phenotype Regulator

2016

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The adult pineal gland is composed of pinealocytes, astrocytes, microglia, and other interstitial cells that have been described in detail. However, factors that contribute to pineal development have not been fully elucidated, nor have pineal cell lineages been well characterized. We applied systematic double, triple and quadruple labeling of cell-specific markers on prenatal, postnatal and mature rat pineal gland tissue combined with confocal microscopy to provide a comprehensive view of the cellular dynamics and cell lineages that contribute to pineal gland development. The pineal gland begins as an evagination of neuroepithelium in the roof of the third ventricle. The pineal primordium initially consists of radially aligned Pax6+ precursor cells that express vimentin and divide at the ventricular lumen. After the tubular neuroepithelium fuses, the distribution of Pax6+ cells transitions to include rosette-like structures and later, dispersed cells. In the developing gland all dividing cells express Pax6, indicating that Pax6+ precursor cells generate pinealocytes and some interstitial cells. The density of Pax6+ cells decreases across pineal development as a result of cellular differentiation and microglial phagocytosis, but Pax6+ cells remain in the adult gland as a distinct population. Microglial colonization begins after pineal recess formation. Microglial phagocytosis of Pax6+ cells is not common at early stages but increases as microglia colonize the gland. In the postnatal gland microglia affiliate with Tuj1+ nerve fibers, IB4+ blood vessels, and Pax6+ cells. We demonstrate that microglia engulf Pax6+ cells, nerve fibers, and blood vessel-related elements, but not pinealocytes. We conclude that microglia play a role in pineal gland formation and homeostasis by regulating the precursor cell population, remodeling blood vessels and pruning sympathetic nerve fibers.

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Section: Resultsmentioning

confidence: 83%

Cellular Basis of Pineal Gland Development: Emerging Role of Microglia as Phenotype Regulator

2016

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“…The functional roles of GABA and glutamate in the pineal gland remain an area of active study, as regards the roles they play in controlling melatonin synthesis [ 34 , 47 – 50 ]. Our studies document expression in pinealocytes and astrocytes and expand on current knowledge of the distribution of genes that mediate GABA and glutamate signaling by detailing the subtypes in which they are expressed ( S11 Fig ), introducing a new layer of complexity.…”

Section: Discussionmentioning

confidence: 99%

Single-cell RNA sequencing of the mammalian pineal gland identifies two pinealocyte subtypes and cell type-specific daily patterns of gene expression

et al. 2018

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The vertebrate pineal gland is dedicated to the production of the hormone melatonin, which increases at night to influence circadian and seasonal rhythms. This increase is associated with dramatic changes in the pineal transcriptome. Here, single-cell analysis of the rat pineal transcriptome was approached by sequencing mRNA from ~17,000 individual pineal cells, with the goals of profiling the cells that comprise the pineal gland and examining the proposal that there are two distinct populations of pinealocytes differentiated by the expression of Asmt, which encodes the enzyme that converts N-acetylserotonin to melatonin. In addition, this analysis provides evidence of cell-specific time-of-day dependent changes in gene expression. Nine transcriptomically distinct cell types were identified: ~90% were classified as melatonin-producing α- and β-pinealocytes (1:19 ratio). Non-pinealocytes included three astrocyte subtypes, two microglia subtypes, vascular and leptomeningeal cells, and endothelial cells. α-Pinealocytes were distinguished from β-pinealocytes by ~3-fold higher levels of Asmt transcripts. In addition, α-pinealocytes have transcriptomic differences that likely enhance melatonin formation by increasing the availability of the Asmt cofactor S-adenosylmethionine, resulting from increased production of a precursor of S-adenosylmethionine, ATP. These transcriptomic differences include ~2-fold higher levels of the ATP-generating oxidative phosphorylation transcriptome and ~8-fold lower levels of the ribosome transcriptome, which is expected to reduce the consumption of ATP by protein synthesis. These findings suggest that α-pinealocytes have a specialized role in the pineal gland: efficiently O-methylating the N-acetylserotonin produced and released by β-pinealocytes, thereby improving the overall efficiency of melatonin synthesis. We have also identified transcriptomic changes that occur between night and day in seven cell types, the majority of which occur in β-pinealocytes and to a lesser degree in α-pinealocytes; many of these changes were mimicked by adrenergic stimulation with isoproterenol. The cellular heterogeneity of the pineal gland as revealed by this study provides a new framework for understanding pineal cell biology at single-cell resolution.

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“…This antibody recognizes a single ∼50 kDa protein band on WBs (Benitez, Castro, Patterson, Muñoz, & Seltzer, ), and intact and degenerated nerve fibers by IHC (Hegarty, Hermes, Yang, & Aicher, ). We used this anti‐Tuj1 antibody to stain nerve fibers in the postnatal pineal gland (Ibañez Rodriguez et al, ; Yu et al, ). Staining observed here matched that of these previous studies.…”

Section: Methodsmentioning

confidence: 96%

Differential response of pineal microglia to surgical versus pharmacological stimuli

Rodriguez

Galiana

Rasmussen

et al. 2018

J of Comparative Neurology

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Microglial cells are one of the interstitial elements of the pineal gland (PG). We recently reported the pattern of microglia colonization and activation, and microglia-Pax6+ cell interactions during normal pineal ontogeny. Here, we describe the dynamics of microglia- Pax6+ cell associations and interactions after surgical or pharmacological manipulation. In adult rats, the superior cervical ganglia (SCG) were exposed, and either bilaterally excised (SCGx) or decentralized (SCGd). In the SCGx PGs, the density of Iba1+ microglia increased after surgery and returned to sham baseline levels 13 days later. Pineal microglia also responded to SCGd, a more subtle denervation. The number of clustered Iba1+/PCNA+/ED1+ microglia was higher four days after both surgeries compared to the sham-operated group. However, the number of Pax6+/PCNA− cells and the percentage of Pax6+ cells contacted by and/or phagocytosed by microglia increased significantly only after SCGx. Separate groups of rats were treated with either bacterial lipopolysaccharides (LPS) or doxycycline (DOX) to activate or inhibit pineal microglia, respectively. Peripheral LPS administration caused an increase in the number of clustered Iba1+/PCNA+/ED1+ microglial cells, and in the percentage of Pax6+ cells associated with and/or engulfed by microglia. In the LPS-treated PGs, we also noted an increase in the number of PCNA+ cells that were Iba1− within the microglial cell clusters. The density of Pax6+ cells did not change after LPS treatment. DOX administration did not influence the parameters analyzed. These data suggest that pineal microglia are highly receptive cells capable of rapidly responding in a differential manner to surgical and pharmacological stimuli.

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GABAergic signaling in the rat pineal gland

Cited by 14 publications

References 53 publications

Cellular Basis of Pineal Gland Development: Emerging Role of Microglia as Phenotype Regulator

Cellular Basis of Pineal Gland Development: Emerging Role of Microglia as Phenotype Regulator

Single-cell RNA sequencing of the mammalian pineal gland identifies two pinealocyte subtypes and cell type-specific daily patterns of gene expression

Differential response of pineal microglia to surgical versus pharmacological stimuli

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