Distribution of retinoic acid receptor-α immunoreactivity in the human hypothalamus

Meng, Qing‐Yuan; Chen, X.-N.; Zhao, Jun; Swaab, Dick F.; Zhou, Jiang‐Ning

doi:10.1016/j.neuroscience.2010.11.058

Cited by 12 publications

(10 citation statements)

References 59 publications

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“…Retinoic acid receptor α is the predominant RAR expressed in the adult central nervous system (Corcoran et al ., ; Agudo et al ., ; Meng et al ., ) and it is becoming increasingly clear that it plays an important role in the maintenance of brain homeostasis (Lane & Bailey, ; Luo et al ., ; Duong & Rochette‐Egly, ). We have shown here that RARα signalling modulates key physiological mechanisms involved in Aβ clearance and how this signalling system is compromised by Aβ, which reduces the synthesis of the endogenous ligand RA.…”

Section: Discussionmentioning

confidence: 99%

Amyloid β inhibits retinoic acid synthesis exacerbating Alzheimer disease pathology which can be attenuated by an retinoic acid receptor α agonist

Goncalves

Clarke

Hobbs

et al. 2013

Eur J of Neuroscience

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The retinoic acid receptor (RAR) α system plays a key role in the adult brain, participating in the homeostatic control of synaptic plasticity, essential for memory function. Here we show that RARα signalling is down-regulated by amyloid beta (Aβ), which inhibits the synthesis of the endogenous ligand, retinoic acid (RA). This results in the counteraction of a variety of RARα-activated pathways that are key in the aetiopathology of Alzheimer's disease (AD) but which can be reversed by an RARα agonist. RARα signalling improves cognition in the Tg2576 mice, it has an anti-inflammatory effect and promotes Aβ clearance by increasing insulin degrading enzyme and neprilysin activity in both microglia and neurons. In addition, RARα signalling prevents tau phosphorylation. Therefore, stimulation of the RARα signalling pathway using a synthetic agonist, by both clearing Aβ and counteracting some of its toxic effects, offers therapeutic potential for the treatment of AD.

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Section: Discussionmentioning

confidence: 99%

Amyloid β inhibits retinoic acid synthesis exacerbating Alzheimer disease pathology which can be attenuated by an retinoic acid receptor α agonist

Goncalves

Clarke

Hobbs

et al. 2013

Eur J of Neuroscience

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“…RA may influence the body's central clock as high levels of RARα expression are found in the vasopressin-expressing neurons of the human SCN ( Meng et al 2011 ) and our own preliminary studies show RARα present in processes and cell bodies in the SCN while mRNA transcript levels cycle with a circadian rhythmicity (Fig. 3 a, b).…”

Section: Retinoic Acid In the Regulation Of Circadian And Seasonal Rhmentioning

confidence: 81%

“… Retinoic acid in the CNS regulates biological rhythms. Retinoic acid (RA) may contribute to the regulation of circadian rhythms in the suprachiasmatic nucleus (SCN), the central clock of the body ( Meng et al 2011 ), the pineal gland ( Herbert and Reiter 1985 ; Guillaumond et al 2005 ), which signals day/night to the rest of the body, and peripheral clocks such as that of the hippocampus ( Golini et al 2012 ). There is also considerable evidence suggesting that RA plays a crucial role in the seasonal rhythms of energy balance in the ventromedial hypothalamus ( Anzano et al 1979 ; Ross et al 2005 ; Shearer et al 2010 ).…”

mentioning

confidence: 99%

The rhythm of retinoids in the brain

Ransom

Morgan

McCaffery

et al. 2013

Journal of Neurochemistry

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The retinoids are a family of compounds that in nature are derived from vitamin A or pro-vitamin A carotenoids. An essential part of the diet for mammals, vitamin A has long been known to be essential for many organ systems in the adult. More recently, however, they have been shown to be necessary for function of the brain and new discoveries point to a central role in processes ranging from neuroplasticity to neurogenesis. Acting in several regions of the central nervous system including the eye, hippocampus and hypothalamus, one common factor in its action is control of biological rhythms. This review summarizes the role of vitamin A in the brain; its action through the metabolite retinoic acid via specific nuclear receptors, and the regulation of its concentration through controlled synthesis and catabolism. The action of retinoic acid to regulate several rhythms in the brain and body, from circadian to seasonal, is then discussed to finish with the importance of retinoic acid in the regular pattern of sleep.We review the role of vitamin A and retinoic acid (RA) as mediators of rhythm in the brain. In the suprachiasmatic nucleus and hippocampus they control expression of circadian clock genes while in the cortex retinoic acid is required for delta oscillations of sleep. Retinoic acid is also central to a second rhythm that keeps pace with the seasons, regulating function in the hypothalamus and pineal gland.

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“…RALDH2 and 3 were raised against whole protein and the RALDH2 antibody has been shown to recognise the human protein (Spiegl et al 2008). All the RAR antibodies are raised against human epitopes and react with human tissue (Meng et al 2011; Lu et al 2005; Alique et al 2007). After washing with 1 × PBS, the tissue was incubated with biotinylated secondary antibodies (Sigma) for 1 h at room temperature.…”

Section: Methodsmentioning

confidence: 99%

High expression of retinoic acid receptors and synthetic enzymes in the human hippocampus

et al. 2011

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Retinoic acid, the active form of the nutrient vitamin A, regulates several facets of neuronal plasticity in the hippocampus, including neurogenesis and synaptic strength, acting via specific retinoic acid receptors (RARs). Essential for conversion of vitamin A to retinoic acid is the enzyme retinaldehyde dehydrogenase (RALDH) and in the rodent hippocampus this is only present in the adjacent meninges where it must act as a locally released paracrine hormone. Little is known though about the expression of RALDHs and RARs in the human hippocampus. This study confirms that RALDH levels are very low in mouse neurons but, surprisingly, strong expression of RALDH protein is detected by immunohistochemistry in hippocampal neurons. The receptors RARα, β and γ were also detected, each receptor exhibiting differing subcellular locations implying their potential regulation of both transcription and non-genomic actions. These results imply an essential function of retinoic acid in the human hippocampus likely to include regulation of neuronal plasticity.

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Distribution of retinoic acid receptor-α immunoreactivity in the human hypothalamus

Cited by 12 publications

References 59 publications

Amyloid β inhibits retinoic acid synthesis exacerbating Alzheimer disease pathology which can be attenuated by an retinoic acid receptor α agonist

Amyloid β inhibits retinoic acid synthesis exacerbating Alzheimer disease pathology which can be attenuated by an retinoic acid receptor α agonist

The rhythm of retinoids in the brain

High expression of retinoic acid receptors and synthetic enzymes in the human hippocampus

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