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Título: | Interactions between neuroactive steroids and reelin haploinsufficiency in Purkinje cell survival |
Autor: | Biamonte, F.; Assenza, G.; Marino, R.; D'Amelio, M.; Panteri, R.; Caruso, D.; Scurati, Samuele; Yagüe, Josué G.; García-Segura, Luis M. CSIC ORCID; Cesa, R.; Strata, Piergiorgio; Melcangi, R. C.; Keller, F. | Fecha de publicación: | 2009 | Editor: | Academic Press | Citación: | Neurobiology of Disease 36: 103-115 (2009) | Resumen: | We determined total Purkinje cell (PC) numbers in cerebella of wild-type (+/+) and heterozygous (rl/+) reeler mice of either sex during early postnatal development; in parallel, we quantified levels of neuroactive steroids in the cerebellum with mass spectrometry. We also quantified reelin mRNA and protein expression with RT-PCR and Western blotting. PC numbers are selectively reduced at postnatal day 15 (P15) in rl/+ males in comparison to +/+ males, +/+ females, and rl/+ females. Administration of 17β-estradiol (17β-E) into the cisterna magna at P5 increases PC numbers in rl/+ males, but not in the other groups; conversely, estrogen antagonists 4-OH-tamoxifen or ICI 182,780 reduce PC numbers in +/+ and rl/+ females, but have no effect in males. Testosterone (T) levels at P5 are much higher in males than in females, reflecting the perinatal testosterone surge in males. In addition, rl/+ male cerebella at P5 show a peculiar hormonal profile in comparison with the other groups, consisting of increased levels of T and 17β-E, and decreased levels of dihydrotestosterone. RT-PCR analysis indicated that heterozygosity leads to a 50% reduction of reelin mRNA in the cerebellum in both sexes, as expected, and that 17β-E upregulates reelin mRNA, particularly in rl/+ males; reelin mRNA upregulation is associated with an increase of all major reelin isoforms. These effects may represent a novel model of how reelin deficiency interacts with variable perinatal levels of neuroactive steroids, leading to gender-dependent differences in genetic vulnerability. © 2009 Elsevier Inc. All rights reserved. | URI: | http://hdl.handle.net/10261/72188 | DOI: | 10.1016/j.nbd.2009.07.001 | Identificadores: | doi: 10.1016/j.nbd.2009.07.001 issn: 0969-9961 |
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