| Autor: |
Pierrot, Nathalie, Tyteca, Donatienne, D'Auria, Ludovic, Dewachter, Ilse, Laetitia El Haylani, Tasiaux, Bernadette, Nathalie Muls, N'Kuli, Francisca, Annie Laquerrière, Demoulin, Jean-Baptiste, Dominique Campion, Jean-Pierre Brion, Courtoy, Pierre J., Kienlen-Campard, Pascal, Octave, Jean-Noël, 3rd IoNS PhD Student Day 2011 |
| Přispěvatelé: |
UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire |
| Jazyk: |
angličtina |
| Rok vydání: |
2013 |
| Popis: |
Neuronal function of Amyloid Precursor Protein (APP) that generates -amyloid peptide remains largely unknown. Expression of human APP (hAPP) in primary cultures of rat neurons decreased HMG-CoA reductase mRNA levels and therefore cholesterol biosynthesis. However, in cultured astrocytes, expression of hAPP did not affect cholesterol biosynthesis. In the nervous system, synaptic transmission and plasticity are supported by synchronous calcium oscillations. These synchronous calcium oscillations are known to be generated by glutamatergic synapses, and are mainly mediated by L-type voltage-dependent calcium channels. Recently, we have reported that expression of human APP in primary culture of rat cortical neurons leads to inhibition of calcium oscillations in all the cells of the network. Since spontaneous neuronal activity is known to be tightly control by cholesterol level in membranes, we wonder whether APP could regulate spontaneous calcium oscillation through a cholesterol dependant mechanism. Indeed, we showed in neurons, expression of hAPP decreased both HMG-CoA reductase and 24-S-cholesterol hydroxylase mRNA levels, leading to inhibition of both cholesterol synthesis and hydroxylation. Reinitiating cholesterol turnover in hAPP expressing neurons rescued synaptic activity reflected by calcium oscillations. Altogether, these results suggest that APP regulates neuronal cholesterol turnover needed for synaptic activity both in vitro and in vivo. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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