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Olivier Thibault

Publications and source records attributed to Olivier Thibault.

4 recordsLinked to original sources
PubMed2006

Chronic 1alpha,25-(OH)2 vitamin D3 treatment reduces Ca2+ -mediated hippocampal biomarkers of aging.

Aging in the hippocampus of several species is characterized by alterations in multiple Ca(2+)-mediated processes, including an increase in L-type voltage-gated Ca(2+) channel (L-VGCC) current, an enhanced Ca(2+)-dependent slow afterhyperpolarization (AHP), impaired synaptic plasticity and elevated Ca(2+) transients. Previously, we found that 1alpha,25-dihydoxyvitamin D(3) (1,25VitD), a major Ca(2+) regulating hormone, down-regulates L-VGCC expression in cultured hippocampal neurons. Here, we tested whether in vivo treatment of aged F344 rats with 1,25VitD would reverse some of the Ca(2+) -mediated biomarkers of aging seen in hippocampal CA1 neurons. As previously reported, L-VGCC currents and the AHP were larger in aged than in young neurons. Treatment with 1,25VitD over 7 days decreased L-VGCC activity in aged rats, as well as the age-related increase in AHP amplitude and duration. In addition, reduced L-VGCC activity was correlated with reduced AHPs in the same animals. These data provide direct evidence that 1,25VitD can regulate multiple Ca(2+)-dependent processes in neurons, with particular impact on reducing age-related changes associated with Ca(2+) dysregulation. Thus, these results may have therapeutic implications and suggest that 1,25VitD, often taken to maintain bone health, may also retard some consequences of brain aging.

Aging↗
PubMed2006

Early and simultaneous emergence of multiple hippocampal biomarkers of aging is mediated by Ca2+-induced Ca2+ release.

Age-dependent changes in multiple Ca2+-related electrophysiological processes in the hippocampus appear to be consistent biomarkers of aging, and several also correlate with cognitive decline. These findings have led to the hypothesis that a common mechanism of Ca2+ dyshomeostasis underlies aspects of aging-dependent brain impairment. However, some key predictions of this view remain untested, including that multiple Ca2+-related biomarkers should emerge concurrently during aging and their onset should also precede/coincide with initial signs of cognitive decline. Moreover, blocking a putative common source of dysregulated Ca2+ should eliminate aging differences. Here, we tested these predictions using combined electrophysiological, imaging, and pharmacological approaches in CA1 neurons to determine the ages of onset (across 4-, 10-, 12-, 14-, and 23-month-old F344 rats) of several established biomarkers, including the increases in the slow afterhyperpolarization, spike accommodation, and [Ca2+]i rise during repetitive synaptic stimulation. In addition, we tested the hypothesis that altered Ca2+-induced Ca2+ release (CICR) from ryanodine receptors, which can be triggered by L-type Ca2+ channels, provides a common source of dysregulated Ca2+ in aging. Results showed that multiple aging biomarkers were first detectable at about the same age (12 months of age; approximately midlife), sufficiently early to influence initial cognitive decline. Furthermore, selectively blocking CICR with ryanodine slowed the Ca2+ rise during synaptic stimulation more in aged rat neurons and, notably, reduced or eliminated aging differences in the biomarkers. Thus, this study provides the first evidence that altered CICR plays a role in driving the early and simultaneous emergence in hippocampus of multiple Ca2+-related biomarkers of aging.

Aging↗
PubMed2002

Sustained Ca2+-induced Ca2+-release underlies the post-glutamate lethal Ca2+ plateau in older cultured hippocampal neurons.

Several studies have shown that a prolonged Ca(2+) elevation follows a glutamate-mediated excitotoxic insult in cultured neurons, and may be associated with impending cell death. Recently, we showed that the prolonged Ca(2+) elevation that emerges as neurons age in culture is specifically linked to an age-related increase in excitotoxic vulnerability. However, the multiple sources of Ca(2+) that contribute to Ca(2+) elevation during and after glutamate exposure are not well understood. Here, we examined the Ca(2+) sources of the age-related prolonged Ca(2+) elevation in cultured hippocampal neurons. Studies with caffeine showed that the ryanodine receptor-dependent releasable pool of Ca(2+) from intracellular stores was similar in older and younger neurons. Thapsigargin, which inhibits intracellular store refilling, did not mimic the age-related prolonged Ca(2+) elevation and, in fact, partially reduced it. Ryanodine, which blocks Ca(2+)-induced Ca(2+)-release (CICR) from stores, completely blocked the age-related prolonged Ca(2+) elevation following glutamate exposure but did not alter maximal Ca(2+) elevation during the glutamate exposure. Thus, we conclude that sustained CICR plays a selective and key role in generating the lethal, age-related, prolonged Ca(2+) elevation, and is the likely mechanism underlying age-related, enhanced vulnerability to excitotoxicity in neurons.

Animals↗