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 17beta-estradiol (17beta-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 17beta-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 17beta-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.

Interactions between neuroactive steroids and reelin haploinsufficiency in Purkinje cell survival / F. Biamonte, G. Assenza, R. Marino, M. D'Amelio, R. Panteri, D. Caruso, S. Scurati, J.G. Yague, L.M. Garcia-Segura, R. Cesa, P. Strata, R.C. Melcangi, F. Keller. - In: NEUROBIOLOGY OF DISEASE. - ISSN 0969-9961. - 36:1(2009 Oct), pp. 103-115. [10.1016/j.nbd.2009.07.001]

Interactions between neuroactive steroids and reelin haploinsufficiency in Purkinje cell survival

D. Caruso;S. Scurati;R.C. Melcangi
Penultimo
;
2009

Abstract

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 17beta-estradiol (17beta-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 17beta-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 17beta-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.
Animals ; Nerve Tissue Proteins ; Cell Survival ; Purkinje Cells ; Aromatase ; Mice, Neurologic Mutants ; Oxidoreductases ; Steroids ; Male ; Cell Adhesion Molecules, Neuronal ; Calcium-Binding Protein, Vitamin D-Dependent ; Estrogens ; Estrogen Antagonists ; Sex Factors ; Brain ; Mice ; Tandem Mass Spectrometry ; Serine Endopeptidases ; Estradiol; RNA, Messenger ; Animals, Newborn ; Testosterone ; Extracellular Matrix Proteins ; Chromatography, Liquid ; Mice, Inbred C57BL ; Female ; Gene Expression Regulation, Developmental ; Receptors, Estrogen
Settore MED/13 - Endocrinologia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/180233
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