Biomedical subjects

V Pallet

Publications and source records attributed to V Pallet.

At least 19 recordsLinked to original sources

PubMed2005

Differential effect of retinoic acid and triiodothyronine on the age-related hypo-expression of neurogranin in rat.

Given the important role of retinoids and thyroid hormone for optimal brain functioning and the tenuous relationship between retinoic acid (RA) and triiodothyronine (T3) signalings, we compared the effects of RA or T3 administrations on RA and T3 nuclear receptors (RAR, RXR and TR) and on their target genes, neuromodulin (GAP43) and neurogranin (RC3) in 24-month-old rats. Quantitative real time PCR and western blot analysis allowed us to verify that retinoid and thyroid signalings and GAP43 and RC3 expression are affected by age. By in situ hybridization we observed a decreased expression of RC3 in hippocampus, striatum and cerebral cortex. RARbeta, RXRbeta/gamma and GAP43 were up-regulated by RA as well as T3 treatment. The abundance of TRalpha/beta mRNA and RC3 expression were only increased by T3 administration in the whole brain. This up-regulator effect of T3 on RC3 was only observed in the striatum. During aging, T3 become a limiting factor alone able to correct the age-related concomitant hypo-activation of retinoid and thyroid signalings and alterations of synaptic plasticity.

Aging↗

PubMed2005

Aging affects the retinoic acid and the triiodothyronine nuclear receptor mRNA expression in human peripheral blood mononuclear cells.

BACKGROUND: Inadequate retinoid status has often been described as occurring with aging. Moreover, subclinical hypothyroid status has also been evoked in the elderly. Several studies performed in animals have described the crucial incidence of age-related hypo-functioning of retinoid and thyroid signalling pathways, particularly in the brain. OBJECTIVE: The aim of the present study was to clarify whether aging modifies retinoid and thyroid signalling in humans. METHODS: Using real-time RT-PCR the relative amount of mRNA of the retinoid (RARalpha, RARgamma and RXRalpha) and thyroid (TRalpha and TRbeta) nuclear receptors in peripheral blood mononuclear cells (PBMC) of young (24-57 years old, n = 22) compared with elderly (69-90 years old, n = 24) healthy subjects was quantitated. Classical plasma parameters used to characterize the retinoid and thyroid status - retinol (ROH), retinol-binding protein (RBP), free triiodothyronine (FT3) and thyroxine (FT4), thyroid-stimulating hormone (TSH) and transthyretin (TTR) - were also assessed. RESULTS: RARgamma expression was significantly decreased in elderly versus young subjects while no modification of the retinoid-related plasma parameters ROH and RBP were emphasized by aging. Concerning thyroid criteria, the elderly exhibited an increase in TSH concentration (+39%) without significant modifications of FT3 and FT4, which indicated an age-related sub-clinical hypothyroidism. Concurrently, the amount of TR mRNA (alpha as well as beta subtypes) was significantly decreased in the elderly. CONCLUSION: These data constitute the first evidence of an age-related hypo-activation of the retinoid and thyroid nuclear pathways in PBMC. Further study of the possible association between the expression of the retinoid and thyroid nuclear receptors and age-related cognitive alterations in humans would be interesting.

Adult↗

PubMed2005

Decreased expression of retinoid nuclear receptor (RAR alpha and RAR gamma) mRNA determined by real-time quantitative RT-PCR in peripheral blood mononuclear cells of hypothyroid patients.

In vivo assessment of the cellular impact of thyroid hormones on target tissues might be of help for physiological studies and to evaluate the consequences of various diseases of the thyroid gland in humans. Given the tenuous relationship between retinoid and tri-iodothyronine (T3) status and that retinoids have also intracellular roles, the aim of this study was to determine the effect of hypothyroidism on the expression of T3 nuclear receptors (TR) and retinoic acid nuclear receptors (RAR, RXR) in human peripheral blood mononuclear cells (PBMC). Using real time RT-PCR, we quantified the relative amount of mRNA of the thyroid (TR alpha and TR beta) and retinoid (RAR alpha, RAR gamma, and RXR alpha) nuclear receptors in PBMC of euthyroid (n = 22) compared with hypothyroid (n = 22) subjects. Classical plasma parameters (free T3 (FT3), free thyroxine (T4) (FT4), thyroid-stimulating hormone (TSH), retinol (ROH), retinol-binding protein (RBP) and transthyretin (TTR)) were also measured. In hypothyroid subjects, the concentration of TSH was elevated, and dramatically low T3 and T4 concentrations were associated with a decrease in the expression of TR beta. Expression of RAR alpha and RAR gamma significantly decreased in hypothyroid versus control subjects, while an increased concentration of ROH was emphasised by hypothyroidism. These results first indicated that primary hypothyroidism induces hypoactivation of the retinoid nuclear pathway in PBMC, which was not predicted by the plasma ROH level. Further investigations will be necessary to evaluate these parameters in very small changes in thyroid hormone production such as mild (subclinical) hypothyroidism.

Base Sequence↗

PubMed2004

Expression of neurogranin and neuromodulin is affected in the striatum of vitamin A-deprived rats.

Our previous data showed that vitamin A deficiency (VAD) induces, in whole brain, a reduced amount of mRNA for brain retinoic acid (RA) and triiodothyronine (T3) nuclear receptors (i.e., RAR, RXR, and TR, respectively), which is accompanied by reduced amounts of mRNA and protein of neurogranin (RC3, a neuronal protein involved in synaptic plasticity) as well as selective behavioral impairment. Given the important role of retinoids for optimal brain functioning, the effects of vitamin A depletion and subsequent administration of RA or T3 on the mRNA levels of RA and T3 nuclear receptors and on two target genes' (RC3 and neuromodulin or GAP43) mRNA and protein levels were examined in the hippocampus, striatum, and cerebral cortex. A quantitative real-time polymerase chain reaction (PCR), in situ hybridization, and Western blot analysis demonstrated that the striatal region is the brain site where both RA and T3 signaling pathways are most affected by VAD. Indeed, rats fed a vitamin A-free diet for 10 weeks exhibited decreased expression of RAR, RXR, TR, RC3, and GAP43 in the striatum. The administration of T3 to these vitamin A-deprived rats reversed the reduction in mRNA levels of RA and T3 nuclear receptors and in mRNA and protein levels of target genes in this region. These data suggest that modifications that appear preferentially in the striatum, a region highly sensitive to vitamin A bioavailability, may contribute to neurobiological alterations and the spatial learning impairment that occurs in vitamin A-deprived animals.

Animals↗

PubMed2004

Retinoic acid reverses the PTU related decrease in neurogranin level in mice brain.

Recent data have shown that fine regulation of retinoid mediated gene expression is fundamentally important for optimal brain functioning in aged mice. Nevertheless, alteration of the thyroid hormone signalling pathway may be a limiting factor, which impedes retinoic acid (RA) from exerting its modulating effect. Mild hypothyroidism is often described in the elderly. Thus, in the present study, it was of interest to determine if RA exerts its neurological modulating effect in mild hypothyroidism. To obtain further insight into this question, mice were submitted to a low propylthiouracyl (PTU) drink (0.05%) in order to slightly reduce the serum level of triiodothyronine (T3). A quantitative evaluation of RA nuclear receptors (RAR, RXR), T3 nuclear receptor (TR) and of neurogranin (RC3, a RA target gene which codes for a protein considered as a good marker of synaptic plasticity) in PTU treated mice injected with vehicle or RA or T3 was carried out. The PTU-related decrease in expression of RAR, RXR and RC3 was restored following RA or T3 administration, as observed in aged mice. The amount of TR mRNA, which was not affected in PTU treated mice, was increased only after T3 treatment as observed in overt hypothyroidism. These results suggest that neurobiological alterations observed in aged mice are probably related to RA and T3 signalling pathway modifications associated, in part, with mild changes in thyroid function.

Animals↗

PubMed2003

Hyperlipidic diets induce early alterations of the vitamin A signalling pathway in rat colonic mucosa.

OBJECTIVE: Dietary factors can be associated with colorectal cancer. Fatty acids modulate gene expression in various tissues, mediated by activation of the peroxisome proliferator activated receptor: PPAR. Vitamin A signalling is mediated by retinoic acid (RA) receptors (RAR) and retinoid X receptors (RXR). The steroid nuclear receptors PPAR, RAR, RXR, are DNA-binding proteins and they induce gene transcription upon activation by specific ligands and interacting with distinct promoter sequences in the target genes. The aim of this study was to investigate the impact of hyperlipidic diets on the expression of PPARg, RXRa and RARb mRNA in rat colon. METHODS: Rats were fed during 4 weeks with the following diets: a cafeteria diet where 60% of the energy was supplied as lipids and a high fat diet (HFD) represented by 25% of a safflower oil (w/w) rich in polyunsaturated fatty acids, mainly n-6. Nuclear receptors mRNA were quantified by realtime RT-PCR with TaqMan probe process or SYBRGreen I chemical. RESULTS: The cafeteria diet and the HFD induced a significant decrease in RARb mRNA: -36% (p<0.02) and -64% (P<0.001) respectively. Simultaneously, an increased expression of PPARg mRNA was observed for cafeteria diet +35% (P<0.05) and for HFD +45% (P<0.05). The level of RXRa mRNA was significantly increased for cafeteria diet: +53% (P<0.0002), while no significant difference in RXRa mRNA was observed in colonic mucosa rats whose fed with the 25% HFD. CONCLUSIONS: These results showed that an hyperlipidic diet could induce early modifications in the pattern of expression of nuclear receptors in rat colon. Many mechanisms could be probably involved but one hypothesis is that a modification of the balance between the nuclear receptors, resulting from an increased expression of PPARg, could induce a decreased expression of RARb in rat colon.

Animals↗

PubMed2002

Relationship between peroxisome proliferator-activated receptor gamma and retinoic acid receptor alpha gene expression in obese human adipose tissue.

OBJECTIVE: To investigate in human adipose tissue a possible relationship between per oxisome proliferator-activated receptor gamma (PPARgamma) and retinoic acid receptor alpha (RARalpha) gene expression, two genes involved in the control of adipocyte differentiation. SUBJECTS: Ten lean control women (age 31-60 y, body mass index (BMI) 18-24.7 kg/m(2)) and an obese group of 15 women (age 27-62 y, BMI 30-57.5 kg/m(2)), of whom 10 subjects were in weight-gain phase and five were in weight-loss phase. MEASUREMENTS: We assessed the relative PPARgamma and RARalpha mRNA levels in subcutaneous abdominal adipose tissue using a real-time PCR method. RESULTS: PPARgamma mRNA level were significantly increased (+91%; P<0.01) in obese women compared to lean control women. In the obese group, we observed a PPARgamma mRNA level 42% lower in weight-loss obese than in weight-gain obese subjects. We obtained a positive correlation (r=0.56; P<0.01) between PPARgamma mRNA level and the BMI of all subjects. Relative mRNA abundance level of RARalpha in subcutaneous adipose tissue of obese subjects is significantly lower than in control subjects (-56%, P<0.01), and a negative correlation was found between PPARgamma and RARalpha mRNA levels in subcutaneous adipose tissue of subjects study (r=-0.75; P<0.01). CONCLUSION: Our findings suggest that obesity is associated with an inverse relationship between PPARgamma and RARalpha expressions in human subcutaneous adipose tissue. Modulations of nuclear receptor profile could be an important event in the body's early adaptive mechanisms promoting adipose tissue plasticity and leading to the onset of obesity.

Adipose Tissue↗

PubMed2002

Transglutamines and endocrine system (minireview).

Transglutaminases catalyze the posttranslation modification of proteins by catalyzing Ca2+ dependent acyl-transfer reaction resulting in the formation of new g-amide bonds between g-carboxamide groups of peptide-bound glutamine residues and various primary amines. Such glutamine residue serves as acyl-donor and the most common acyl-acceptors are e-amino groups of peptide-bound lysine residues or primary amino groups of some naturally occurring polyamines, like putrescine or spermidine. The active site of cysteine reacts first with the g-carboxamide group of glutamine residue to form the acyl-enzyme intermediate under the release of ammonia. In the second step, the complex reacts with a primary amine to form an isopeptide bond and liberate the reactivated enzyme. The presence of transglutaminases has been observed in various endocrine glands such as human pituitary, which was investigated by immunohistochemical methods using specific antibodies. A significant increase in the expression and activity of tissue transglutaminase was observed during involution of thymus. In the genital tract of the male rat two different forms of the enzyme transglutaminase could be identified and characterized. the presence of p53 and tissues transglutaminase gene expressions in human normal and pathologic adrenal tissues. The Ca2+-responsive enzyme transglutaminase, which catalyzes the cross-bridging of proteins, was found in pancreatic islet cells.

Animals↗

PubMed2001

Alleviation of a selective age-related relational memory deficit in mice by pharmacologically induced normalization of brain retinoid signaling.

Vitamin A and its derivatives, the retinoids, have been implicated recently in the synaptic plasticity of the hippocampus and might therefore play a role in associated cognitive functions. Acting via transcription factors, retinoids can regulate gene expression via their nuclear receptors [retinoic acid receptors (RARs) and retinoid X receptors]. In a series of experiments, the present study investigated the possible role of age-related downregulation of retinoid-mediated transcription events in the cognitive decline seen in aged mice. We observed that the brain (and hippocampal) levels of retinoid receptors and the expression of specific associated target genes were restored to presenescent (adult) levels in aged mice after acute administration (150 microg/kg, s.c.) of retinoic acid (RA). These effects of RA, however, could be abolished by the coadministration of an RAR antagonist. RA was also demonstrated to alleviate the age-related deficit in the CA1 long-term potentiation efficacy of aged mice in vivo. Moreover, RA was found to alleviate completely the performance deficit of aged mice to the control level in a two-stage spatial discrimination paradigm designed to assess relational memory. This promnesic effect of RA was again susceptible to abolition by RAR antagonist treatment. The parallel molecular, cellular, and behavioral correlates associated with the decrease of retinoid receptor expression and its normalization demonstrated here suggest that the fine regulation of retinoid-mediated gene expression is fundamentally important to optimal brain functioning and higher cognition. Specifically, a naturally occurring dysregulation of retinoid-mediated molecular events might be a potential etiological factor for cognitive deterioration during senescence.

Aging↗

PubMed2001

A retinoic acid receptor antagonist suppresses brain retinoic acid receptor overexpression and reverses a working memory deficit induced by chronic ethanol consumption in mice.

BACKGROUND: Chronic ethanol consumption induces disorders in the biosynthesis of retinoic acid, an active derivative of vitamin A. Recent evidence suggests that an alteration in the retinoic acid signaling pathway leads to impairments in learning and memory in adult mice. We have previously shown that chronic ethanol consumption in mice produces an increased expression of the brain retinoic acid receptor beta (RARbeta) mRNA. These results prompted us to examine whether suppressing the overexpression of retinoid receptors in alcohol-treated mice by RAR antagonist administration would reverse their cognitive impairment. METHODS: After 10 months of ethanol consumption (12% v/v in drinking water), C57BL/6 mice were submitted to a working memory task in a T-maze. Then, mice of the control and the ethanol-treated groups received an RARbeta antagonist (CD2665 0.6 mg/kg) for 22 days. The behavioral effect of CD2665 administration was evaluated on a spontaneous alternation task and the neurochemical effect was measured by quantifying the mRNA expression of RARalpha, RARbeta, retinoid X receptor (RXRbeta/gamma) and tissue transglutaminase (tTG; a retinoic acid-target gene). RESULTS: Mice submitted to ethanol treatment exhibited a progressive decrease in spontaneous alternation rates over successive trials. Moreover, these mice displayed an increased expression of brain RARbeta and RXRbeta/gamma mRNA, together with an increased level of tTG mRNA and enzymatic activity. The administration of CD2665 to alcohol-treated mice totally reversed the working memory deficit and suppressed the overexpression of brain RARbeta, RXRbeta/gamma and tTG mRNA, whereas the same treatment in control mice decreased only the RARbeta mRNA level without affecting memory performance. CONCLUSION: These data point to the potential role of the retinoid signaling pathway in memory processes and suggest that the overexpression of brain RARbeta and RXRbeta/gamma could be responsible, at least in part, for some memory impairments observed during chronic ethanol consumption.

Alcohol Drinking↗

PubMed2001

Effect of a pharmacological activation of PPAR on the expression of RAR and TR in rat liver.

It has recently been shown that high-fat diets induce the expression of peroxisome proliferator-activated receptor (PPAR) with a concomitant decrease in expression of retinoic acid (RAR) and triiodothyronine (TR) receptors in rat liver. The authors have suggested that PPAR activation may be responsible for these modifications in nuclear receptor expression. With the aim of gaining further insight into a possible relationship between the patterns of expression of these receptors, we have examined, using a pharmacological model, the effect of a strong and specific PPAR activation induced by bezafibrate, a peroxisome proliferator agent. Activation of PPAR was evaluated by quantifying PPAR alpha mRNA and acyl-CoA oxidase mRNA. The expression of RAR and TR was determined by assaying the binding properties of these nuclear receptors and by quantifying the mRNA level of RAR beta and TR alpha1,beta1 isoforms. After a 10 day treatment of young rats, induction of PPAR (PPAR alpha mRNA was increased by 40% [P< 0.05 and acyl-CoA oxidase mRNA by 411% [P<0.001]) and a concomitant decrease of RAR and TR expression (Maximal Binding Capacity was decreased by 21 and 26%, respectively [P<0.05]) in the liver was observed. RXR alpha mRNA expression was unchanged by treatment. Cross-talk between RAR, TR and PPAR signalling pathways may be implicated in the new patterns of nuclear receptor expression observed. The decreased expression of RAR and TR reported here could provide a novel element for the understanding of the link between PPAR and tumorigenesis in rat liver.

Acyl-CoA Oxidase↗

PubMed2001

Effect of a pharmacological activation of PPAR on the expression of RAR and TR in rat liver.

It has recently been shown that high-fat diets induce the expression of peroxisome proliferator-activated receptor (PPAR) with a concomitant decrease in expression of retinoic acid (RAR) and triiodothyronine (TR) receptors in rat liver. The authors have suggested that PPAR activation may be responsible for these modifications in nuclear receptor expression. With the aim of gaining further insight into a possible relationship between the patterns of expression of these receptors, we have examined, using a pharmacological model, the effect of a strong and specific PPAR activation induced by bezafibrate, a peroxisome proliferator agent. Activation of PPAR was evaluated by quantifying PPARalpha mRNA and acyl-CoA oxidase mRNA. The expression of RAR and TR was determined by assaying the binding properties of these nuclear receptors and by quantifying the mRNA level of RARbeta and TRalpha1,beta1 isoforms. After a 10 day treatment of young rats, induction of PPAR (PPARalpha mRNA was increased by 40% [P < 0.05 and acyl-CoA oxidase mRNA by 411% [P<0.001]) and a concomitant decrease of RAR and TR expression (Maximal Binding Capacity was decreased by 21 and 26%, respectively [P<0.05]) in the liver was observed. RXRalpha mRNA expression was unchanged by treatment. Cross-talk between RAR, TR and PPAR signalling pathways may be implicated in the new patterns of nuclear receptor expression observed. The decreased expression of RAR and TR reported here could provide a novel element for the understanding of the link between PPAR and tumorigenesis in rat liver.

Animals↗

PubMed2000

High-fat diets affect the expression of nuclear retinoic acid receptor in rat liver.

The purpose of this study was to differentiate between the effects of the amount and the type of dietary lipids on the expression of the retinoic acid receptor (RAR), but also the peroxisome proliferator-activated receptor (PPAR) and the receptor of the 9-cis retinoic acid (retinoid X receptor (RXR)) in rat liver. Six groups of eight rats (5-weeks old) were fed during 4 weeks on the following diets: control 50 g vegetable oil/kg, high-fat diet 250 g vegetable oil/kg. These oils were either coconut oil (rich in saturated fatty acids) or olive oil (rich in monounsaturated fatty acids) or safflower oil (rich in polyunsaturated fatty acids, mainly as n-6). The three high-fat diets induced a significant decrease of the maximal binding capacity of RAR and of the abundance of RAR beta mRNA. Simultaneously, an increased expression of PPAR alpha mRNA was observed while no significant difference on abundance of RXR alpha mRNA was observed. The mechanisms involved are probably multiple, but one hypothesis is that a modification of the equilibrium between the nuclear receptors, resulting from an increased expression of PPAR, induces a decreased expression of RAR in rat liver.

Animals↗

PubMed1998

Expression of retinoic acid, triiodothyronine, and glucocorticoid hormone nuclear receptors is decreased in the liver of rats fed a hypercholesterolemia-inducing diet.

Several studies have shown that dietary factors modulate cell signaling pathways. The aim of this study was to determine whether a hypercholesterolemia-inducing diet rich in saturated fat and cholesterol modifies rat liver expression of the nuclear receptors of retinoic acid (RAR), triiodothyronine (TR), and glucocorticoid hormone (GR), which are transcriptional factors. The experimental diet contained coconut oil 25 g/100 g as a source of lipids, cholesterol 1 g/100 g, and cholic acid 0.5 g/100 g, and the control diet contained olive oil 5 g/100 g. After 26 days of feeding the hypercholesterolemia-inducing diet, a lower binding capacity of the nuclear receptors and a smaller amount of their mRNA were observed. Moreover, the activities of malic enzyme (ME) and tyrosine aminotransferase (TAT), whose gene promotors contain a response element to TR and GR, respectively, were significantly decreased. These changes occurred in a cellular environment characterized by a high level of cholesterol and free fatty acids (FFAs). Thus, two nonexclusive hypotheses can be proposed to explain this decreased expression of nuclear receptors, one emphasizing the effect of lipidic components on the cellular amount of receptor ligands (retinoic acid [RA] and triiodothyronine [T3]), the other emphasizing a modification of the balance between nuclear receptors that could impede the upregulation of TR and RAR.

Animals↗

PubMed1997

Aging decreases retinoic acid and triiodothyronine nuclear expression in rat liver: exogenous retinol and retinoic acid differentially modulate this decreased expression.

The expression of nuclear receptors of retinoic acid (RAR) and triiodothyronine (TR) was analyzed in the liver of rats aged 2.5 (young), 6 (adult) and 24 (aged) months. In aged rats, decreased binding properties, binding capacity (Cmax) and affinity (Ka), of nuclear receptors were observed. This resulted, at least in part, from decreased transcription of receptor genes in that the amount of their mRNA also decreased. Moreover, the activity of malic enzyme (ME) and tissue transglutaminase (tTG), whose genes are TR and RAR responsive, respectively, was reduced in aged rats. These results are in agreement with the decreased binding capacity of these receptors. An inducer-related increase of RAR and TR expression was observed 24 h after a single dose of retinoic acid administration (5 mg/kg), while retinol administration (retinyl palmitate, 13 mg/kg) was without incidence on nuclear receptor expression in aged rats.

Aging↗

PubMed1997

Aging decreases the abundance of retinoic acid (RAR) and triiodothyronine (TR) nuclear receptor mRNA in rat brain: effect of the administration of retinoids.

Aging is accompanied by troubles resulting from changes in hormonal and nutritional status. Therefore, the abundance of mRNA coding for triiodothyronine (TR) and retinoic acid (RA) nuclear receptors was studied in the brain of young, adult and aged (2.5, 6 and 24 months, respectively) rats. In the brain of aged rats, there was a lower abundance of TR and RAR mRNA and a lower activity of tissue transglutaminase (tTG), an enzyme the gene of which is a target for retinoids. Administration of RA in these rats restored TR and RAR mRNA and the activity of tTG in the brain. The importance of these observations to the function of the aged brain is discussed.

Age Factors↗

PubMed1997

Age-related decreases in mRNA for brain nuclear receptors and target genes are reversed by retinoic acid treatment.

Ageing is accompanied by certain problems resulting from changes of hormonal status, in particular thyroid hormone (T3) status and vitamin A status. Since retinoic acid (RA), the active metabolite of vitamin A, and T3 play physiological roles in the adult brain, the effect of ageing on the amounts of mRNA for retinoic acid (RAR and RXR) and triiodothyronine (TR) nuclear receptors were studied. Also, the expression of RA and T3 target genes, tissue transglutaminase (tTG) and neurogranin (RC3), was measured in the whole brain and in the hippocampus of mice. Relative to young (3 months) mice, aged (22 months) mice exhibited lower amounts of RAR, RXR and TR mRNA concomitantly with a lower expression of tTG and RC3. RA administration to old mice (24 h before sacrifice) was able to restore the amount of mRNA of nuclear receptors and of RC3. It is hypothesized that a decrease in the cellular action of RA and T3 could play a role, via a decrease in the expression of RC3, in the alteration of synaptic plasticity occurring in aged mice.

Aging↗

PubMed1996

Chronic ethanol consumption increases the amount of mRNA for retinoic acid and triiodothyronine receptors in mouse brain.

It is known that alcohol induces disorders in the metabolism of retinoids and particularly in the biosynthetic pathways of retinoic acid (RA). Since RA has, along with other hormones and particularly triiodothyronine (T3), a physiological role in the adult brain, the effect of chronic exposure to alcohol on RA and T3 status was investigated. The amounts of RA receptor (RAR) and T3 receptor (TR) mRNAs were quantified and the activity of the 'tissue' transglutaminase (tTG; an RA-dependent enzyme) was assayed in the brain of mice following chronic ethanol consumption (CEC; 12% v/v for 6-10 months). Compared to controls, ethanol-treated mice exhibited increased amounts of RAR and TR mRNAs together with an increase in tTG activity. It is hypothesized that the enhanced cellular action of RA and T3 could play a role in the previously described brain damages induced by CEC.

Alcoholism↗