RORalpha, a Key to the Development and Functioning of the Brain

Jolly, Sarah; Journiac, Nathalie; Garabedian, Béatrice Vernet-der; Mariani, Jean

doi:10.1007/s12311-011-0339-1

Cited by 20 publications

(16 citation statements)

References 10 publications

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“…have been posited. For example, Miller and colleagues (Miller et al 2013) referenced evidence of the role of RORA in protection against neurodegeneration in the face of oxidative stress (Jolly et al 2012). They hypothesized that RORA could modify neurodegeneration and functional abnormalities in areas of the brain associated with PTSD and related psychopathology.…”

Section: Discussionmentioning

confidence: 99%

RORA and posttraumatic stress trajectories: main effects and interactions with childhood physical abuse history

et al. 2015

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BackgroundLongitudinal studies of posttraumatic stress (PTS) have documented environmental factors as predictors of trajectories of higher, versus lower, symptoms, among them experiences of childhood physical abuse. Although it is now well-accepted that genes and environments jointly shape the risk of PTS, no published studies have investigated genes, or gene-by-environment interactions (GxEs), as predictors of PTS trajectories. The purpose of this study was to fill this gap.Methods and MaterialsWe examined associations between variants of the retinoid-related orphan receptor alpha (RORA) gene and trajectory membership among a sample of predominantly non-Hispanic Black urban adults (N = 473). The RORA gene was selected based on its association with posttraumatic stress disorder (PTSD) in the first PTSD genome wide association study. Additionally, we explored GxEs between RORA variants and childhood physical abuse history.ResultsWe found that the minor allele of the RORA SNP rs893290 was a significant predictor of membership in a trajectory of consistently high PTS, relatively to a trajectory of consistently low PTS. Additionally, the GxE of rs893290 with childhood physical abuse was significant. Decomposition of the interaction showed that minor allele frequency was more strongly associated with membership in consistently high or decreasing PTS trajectories, relative to a consistently low PTS trajectory, among participants with higher levels of childhood physical abuse.ConclusionThe results of the study provide preliminary evidence that variation in the RORA gene is associated with membership in trajectories of higher PTS and that these associations are stronger among persons exposed to childhood physical abuse. Replication and analysis of functional data are needed to further our understanding of how RORA relates to PTS trajectories.

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Section: Discussionmentioning

confidence: 99%

RORA and posttraumatic stress trajectories: main effects and interactions with childhood physical abuse history

et al. 2015

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“…Besides the cerebellum, RORα is expressed in other brain regions although its role there remains less studied. In addition to neurons, glial cells, particularly astrocytes, have been found to express RORα, possibly to regulate inflammatory and oxidative pathways (Jolly et al, 2012). New animal models with time-, cell type and region-dependent manipulations of RORα are needed to better appreciate the possible multiple roles of the gene.…”

Section: Animal Models Of Cerebellum Dysfunctionmentioning

confidence: 99%

Pre-clinical models of neurodevelopmental disorders: focus on the cerebellum

Shevëlkin¹,

Ihenatu

Pletnikov³

2014

Reviews in the Neurosciences

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Recent studies have advanced our understanding of the role of the cerebellum in non-motor behaviors. Abnormalities in the cerebellar structure have been demonstrated to produce changes in emotional, cognitive, and social behaviors resembling clinical manifestations observed in patients with autism spectrum disorders (ASD) and schizophrenia. Several animal models have been used to evaluate the effects of relevant environmental and genetic risk factors on the cerebellum development and function. However, very few models of ASD and schizophrenia selectively target the cerebellum and/or specific cell types within this structure. In this review, we critically evaluate the strength and weaknesses of these models. We will propose that the future progress in this field will require time- and cell type-specific manipulations of disease-relevant genes, not only selectively in the cerebellum, but also in frontal brain areas connected with the cerebellum. Such information can advance our knowledge of the cerebellar contribution to non-motor behaviors in mental health and disease.

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“…Additionally, it has been shown that RORα is an important molecular player in diverse pathological processes including oxidative stress-induced apoptosis and cerebral hypoxia, both in neurons and astrocytes, due to its neuroprotective properties [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

“…Studies using staggerer mice, which have a 122 bp deletion in the RORα gene, allowed the identification of several functions of this nuclear receptor, both in the periphery and in the CNS. Interestingly, a massive cerebellar neurodegeneration leading to severe ataxia was also observed in these mice [ 44 ].…”

Section: Clock Genes In Glial Cellsmentioning

confidence: 99%

The Role of Mammalian Glial Cells in Circadian Rhythm Regulation

Chi-Castañeda

Ortega

2017

Neural Plasticity

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Circadian rhythms are biological oscillations with a period of about 24 hours. These rhythms are maintained by an innate genetically determined time-keeping system called the circadian clock. A large number of the proteins involved in the regulation of this clock are transcription factors controlling rhythmic transcription of so-called clock-controlled genes, which participate in a plethora of physiological functions in the organism. In the brain, several areas, besides the suprachiasmatic nucleus, harbor functional clocks characterized by a well-defined time pattern of clock gene expression. This expression rhythm is not restricted to neurons but is also present in glia, suggesting that these cells are involved in circadian rhythmicity. However, only certain glial cells fulfill the criteria to be called glial clocks, namely, to display molecular oscillators based on the canonical clock protein PERIOD, which depends on the suprachiasmatic nucleus for their synchronization. In this contribution, we summarize the current information about activity of the clock genes in glial cells, their potential role as oscillators as well as clinical implications.

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RORalpha, a Key to the Development and Functioning of the Brain

Cited by 20 publications

References 10 publications

RORA and posttraumatic stress trajectories: main effects and interactions with childhood physical abuse history

RORA and posttraumatic stress trajectories: main effects and interactions with childhood physical abuse history

Pre-clinical models of neurodevelopmental disorders: focus on the cerebellum

The Role of Mammalian Glial Cells in Circadian Rhythm Regulation

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