Disruption of the retinoid signalling pathway causes a deposition of amyloid β in the adult rat brain

Corcoran, Jonathan; So, Po Lin; Maden, Malcolm

doi:10.1111/j.1460-9568.2004.03563.x

Cited by 177 publications

(138 citation statements)

References 53 publications

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“…Furthermore, these post-natal effects of experimental retinoid manipulations incur minimal anatomical changes (in comparison to manipulations during the prenatal period) whereas behavioral effects are quite profound. Intriguingly, the cortex of retinoic acid deprived rats is characterized by beta-amyloid accumulation and other changes that parallel those in Alzheimer' disease [83]. Additionally, normal memory loss in aging rats can be alleviated by vitamin A therapy [84].…”

Section: Retinoids and Cd38mentioning

confidence: 99%

Are retinoids potential therapeutic agents in disorders of social cognition including autism?

et al. 2011

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Edited by Sergio Papa, Gianfranco Gilardi and Wilhelm JustKeywords: Autism spectrum disorder (ASD) All-trans retinoic acid (ATRA) CD38 Oxytocin Polymorphism a b s t r a c t Increasing evidence suggests that the nonapeptide, oxytocin (OT), helps shape social and affiliative behaviors not only in lower mammals but also in humans. Recently, an essential mediator of brain OT release has been discovered, ADP-ribosyl cyclase and/or CD38. We have subsequently shown that polymorphisms across the CD38 gene are associated with autism spectrum disorders (ASD). Notably, CD38 expression in lymphoblastoid cells (LBC) is reduced in cell lines derived from ASD subjects compared to parental cell lines. Intriguingly, a correlation was observed between CD38 expression and measures of social function in ASD. Finally, we have shown that all-trans retinoic acid (ATRA), a known inducer of CD38 transcription, can rescue low CD38 expressing LBC lines derived from ASD subjects and restore normal levels of transcription of this ectoenzyme providing 'proof of principle' in a peripheral model that retinoids are potential therapeutic agents in ASD. Ó 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. OxytocinClassically, the nonapeptide oxytocin (OT) has been viewed as a hypothalamic neuropeptide that is released into the general circulation from the neural lobe of the pituitary, inducing uterine contractions during parturition and milk ejection during lactation. OT is derived from a pre-prohormone precursor that is synthesized in the hypothalamus and stored in vesicles at the posterior pituitary for storage and subsequent release into the bloodstream (see [1] for comprehensive review of the oxytocin receptor system). OT and social behaviorBeyond the long-known peripheral effects of OT, a wealth of animal studies have elaborated the role of OT, or their analogues such as isotocin and vasotocin [2], in molding social behavior from fish to mammals [3]. In the past few years the role of OT has also been examined in our own species, and similar to what has been learned from animal studies, it appears that this nonapeptides also influence social behaviors in humans [4,5]. Indeed, OT has been suggested as the 'great facilitator of life' in a recent review [6].In humans, intranasal administration of OT has been shown to increase trust [7], facilitate mind-reading [8], enhance human memory for social identity [9], increase positive communication between couples [10], increase gaze to the eye region [11] and increase generosity [12]. Intriguingly, OT plasma levels have been linked to individual patterns of maternal-fetal attachment [13] and salivary OT levels were associated with bonding to own parents and inversely related to psychological distress, particularly depressive symptoms [14]. Social anxiety symptom severity, adjusted for age and gender in a healthy group of subjects, was associated with higher plasma oxytocin levels [15]. Imaging studies reinforce the role of OT in influencing human social ...

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Section: Retinoids and Cd38mentioning

confidence: 99%

Are retinoids potential therapeutic agents in disorders of social cognition including autism?

et al. 2011

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“…Il a ete montre que l'hypoactivite de la voie de signalisation des retinoïdes entraîne la formation anormale et le depôt des petides Ab (Corcoran et al, 2004). Ceci a en particulier ete montre chez des rats carences en vitamine A. Apres consommation pendant 1 an d'une alimentation totalement depourvue de cette vitamine, les animaux presentaient une hypoactivation de la voie de signalisation de la vitamine A, et avaient developpe des depots b-amyloïdes dans leur cerveau.…”

Section: Vitamine a Et Maladie D'alzheimerunclassified

Vitamine A et vieillissement cérébral

Pallet

Enderlin

2011

OCL

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La vitamine A est une vitamine liposoluble qui presente des rôles importants dans differents tissus de l'organisme. Elle est impliquee dans la vision, dans le maintien de l'integrite des surfaces epitheliales, dans l'immunite, la reproduction ou encore dans la croissance et le developpement (Blomhoff et Blomhoff, 2006). En dehors de son rôle dans la vision, la vitamine A agit principalement par l'intermediaire de son metabolite l'acide retinoïque (AR) qui, en se liant a des recepteurs nucleaires, regule l'expression de genes dans les tissus cibles.Il est bien connu que les retinoïdes, et en particulier l'AR, jouent un rôle capital dans le developpement du systeme nerveux central, mais ce n'est que recemment que son action dans le cerveau adulte a retenu l'attention des scientifiques. Les donnees actuellement disponibles sur ce sujet suggerent qu'une regulation tres fine de l'expression des genes cibles de l'AR est fondamentale pour des fonctions cerebrales optimales, telles que la plasticite synaptique, l'apprentissage et la memoire. Plus recemment encore, des donnees provenant de plusieurs etudes mettent en evidence l'implication de la voie de signalisation des retinoïdes dans l'etiologie de la maladie d'Alzheimer (MA). Metabolisme et transport de la vitamine APour les mammiferes superieurs la vitamine A provient exclusivement de l'alimentation : soit sous forme de vitamine preformee (dans sa forme majoritaire il s'agit de retinol esterifie par des acides gras a longues chaînes comme le palmitate de retinyle par exemple) dans les produits animaux, ou bien sous forme de carotenoïdes provitaminiques tels que le b-carotene, a-carotene, b-cryptoxanthine, presents dans les aliments d'origine vegetale (figure 1). On recommande actuellement que 60 % de l'apport en vitamine A soit sous la forme de carotenoïdes (sources vegetales) et 40 % sous forme de retinol (sources animales) (Cordain et al., 2005). L'ester de retinol (RE) doitêtre hydrolyse avant d'être absorbe au niveau intestinal. L'efficacite d'absorption est meilleure pour la vitamine A preformee (80 a 90 %) que pour les carotenoïdes (50-60 %). Le carotene est converti en retinol au niveau de la muqueuse intestinale. Le retinol est ensuite esterifie dans les cellules de la muqueuse par la LRAT (Lecithin : retinol acyltransferase), le RE resultant de cette catalyse est incorpore dans les chylomicrons et absorbe via le systeme lymphatique (Harrison, 2005). Dans des conditions nutritionnelles normales, la plupart de la vitamine A de l'organisme est stockee dans le foie (essentiellement sous forme de retinyl ester : RE) pour une part dans les hepatocytes et pour la majorite sous forme de gouttelettes lipidiques dans les cellules etoilees du foie (encore appelees Abstract: To date, convergent data on the role of retinoic acid in the mature brain have established that this molecule, which acts as a hormone, helps to preserve cerebral plasticity by controlling dendritic spine density as well as hippocampal neurogenesis. Deterioration in cerebral plasticity seems to be ...

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“…Retinoid receptors are preferentially located in structures involved in cognition (cerebral cortex, amygdala, hypothalamus, hippocampus and striatum), and there is evidence that they participate in synaptic plasticity as well as in learning and memory processing (Lane and Bailey 2005). Accordingly, several studies have already demonstrated that disruption of retinoid signaling pathways is directly implicated in the pathophysiology of Alzheimer's disease, namely in the amyloidogenic pathway (Misner et al 2001;Husson et al 2006;Corcoran et al 2004). Whether obesity-related adipocyte dysfunction contributes to this central retinoid disruption remains unclear.…”

Section: Visfatin and Rbp-4mentioning

confidence: 99%

Obesity as a risk factor for Alzheimer’s disease: the role of adipocytokines

2014

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Alzheimer's disease is the leading cause of dementia and the most prevalent neurodegenerative disease. It is an aging-related multi-factorial disorder and growing evidence support the contribution of metabolic factors to what was formerly thought to be a centrally mediated process. Obesity has already been recognized as an important player in the pathogenesis of this type of dementia, independently of insulin resistance or other vascular risk factors. Although the exact underlying mechanisms are still unknown, adipocyte dysfunction and concomitant alteration in adipocyte-derived protein secretion seem to be involved, since these adipocytokines can cross the blood-brain barrier and influence cognitive-related structures. Very few studies have assessed the role of adipocytokines dysfunction on cognitive impaired patients and yielded contradictory results. Interestingly, extensive research on the central effects of leptin in Alzheimer's diseasetransgenic mice has demonstrated its capacity to enhance synaptic plasticity and strength, as well as to prevent betaamyloid deposition and tau phosphorylation. In addition, adiponectin, the most abundant adipocytokine whose levels are inversely correlated to adiposity, has shown to be neuroprotective to hippocampal cells. Many other adipose-derived cytokines have mainly pro-inflammatory properties, being able to trigger and/or enhance central inflammatory cascades and also to influence the secretion of other adipocytokines involved in cognition. This paper pretends to review the existing evidence on the contribution of adipocytokines dysfunction to the increased risk of dementia associated with midlife obesity, unraveling its insulin-independent effects on cognition.

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Disruption of the retinoid signalling pathway causes a deposition of amyloid β in the adult rat brain

Cited by 177 publications

References 53 publications

Are retinoids potential therapeutic agents in disorders of social cognition including autism?

Are retinoids potential therapeutic agents in disorders of social cognition including autism?

Vitamine A et vieillissement cérébral

Obesity as a risk factor for Alzheimer’s disease: the role of adipocytokines

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