Paul Higueret | PubMed Health

PubMed2003

Chronic ethanol consumption restores the age-related decrease in neurogranin mRNA level in the hippocampus of mice.

Neurogranin (Ng) is a Ca(2+)-sensitive calmodulin-binding neuron-specific protein that has been implicated in the regulation of numerous post-synaptic signalling pathways. Here, we investigate the effects of 5 months low level ethanol consumption (approximately 20% of total calories intake) on Ng mRNA expression in the brain of adult (approximately 7-8 months) and aged (approximately 21-22 months) mice using in situ hybridization histochemistry. Results showed that ageing was accompanied by a decrease in amounts of mRNA coding for Ng, especially in the hippocampus (approximately 25% of adults) known to play a critical role in higher cognitive functions. Chronic ethanol consumption restored this decline up to pre-senescent (adult) levels without altering Ng mRNA levels in adult mice. On the basis of recent data indicating a central role for Ng in the regulation of hippocampal synaptic plasticity and spatial learning, our results suggest that moderate ethanol consumption might have a beneficial influence on cognitive deterioration during senescence. Such a possibility is in fact congruent with recent follow-up studies conducted in elderly people.

Aging↗

PubMed2003

Triiodothyronine administration reverses vitamin A deficiency-related hypo-expression of retinoic acid and triiodothyronine nuclear receptors and of neurogranin in rat brain.

Recent studies have revealed that retinoids play an important role in the adult central nervous system and cognitive functions. Previous investigations in mice have shown that vitamin A deficiency (VAD) generates a hypo-expression of retinoic acid (RA, the active metabolite of vitamin A) receptors and of neurogranin (RC3, a neuronal protein involved in synaptic plasticity) and a concomitant selective behavioural impairment. Knowing that RC3 is both a triiodothyronine (T3) and a RA target gene, and in consideration of the relationships between the signalling pathways of retinoids and thyroid hormones, the involvement of T3 on RA signalling functionality in VAD was investigated. Thus, the effects of vitamin A depletion and subsequent administration with RA and/or T3 on the expression of RA nuclear receptors (RAR, RXR), T3 nuclear receptor (TR) and on RC3 in the brain were examined. Rats fed a vitamin A-deficient diet for 10 weeks exhibited a decreased expression of RAR, RXR and TR mRNA and of RC3 mRNA and proteins. RA administration to these vitamin A-deficient rats reversed only the RA hypo-signalling in the brain. Interestingly, T3 is able to restore its own brain signalling simultaneously with that of vitamin A and the hypo-expression of RC3. These results obtained in vivo revealed that one of the consequences of VAD is a dysfunction in the thyroid signalling pathway in the brain. This seems of crucial importance since the down regulation of RC3 observed in the depleted rats was corrected only by T3.

Animals↗