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.

Biamonte, F., Assenza, G., Marino, R., D'amelio, M., Panteri, R., Caruso, D., Scurati, S., Yougue, J. G., Garcia Segura, L. M., Cesa, R., Strata, P., Melcangi, R. C., Keller, F., Interactions between neuroactive steroids and reelin haploinsufficiency in Purkinje cell survival., <<NEUROBIOLOGY OF DISEASE>>, 2009; 36 (Ottobre): 103-115. [doi:10.1016/j.nbd.2009.07.001] [http://hdl.handle.net/10807/28767]

Interactions between neuroactive steroids and reelin haploinsufficiency in Purkinje cell survival.

Biamonte, Filippo;
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.
eng
http://dx.medra.org/10.1016/j.nbd.2009.07.001
Biamonte, F., Assenza, G., Marino, R., D'amelio, M., Panteri, R., Caruso, D., Scurati, S., Yougue, J. G., Garcia Segura, L. M., Cesa, R., Strata, P., Melcangi, R. C., Keller, F., Interactions between neuroactive steroids and reelin haploinsufficiency in Purkinje cell survival., <>, 2009; 36 (Ottobre): 103-115. [doi:10.1016/j.nbd.2009.07.001] [http://hdl.handle.net/10807/28767]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10807/28767
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact