Sex Effect in Mouse and Human Prion Disease

Abstract

Sex effect on the incubation period of variant Creutzfeldt-Jakob disease (vCJD) disease in human and ME-7 murine models was investigated. In the 167 vCJD cases reported in the United Kingdom as of January 2009, age at onset was significantly lower in female patients (by 2 years) than in male patients after stratification on birth cohort. In C57/Bl6N mice infected with ME-7 scrapie strain, incubation was shorter in female than in male mice. The incubation period increased in castrated male mice after intraperitoneal infection but not after intracerebral inoculation. In the absence of androgen receptors, the incubation period for prion disease increased after intraperitoneal inoculation. In ovariectomized or estrogen receptor alpha-defective female mice, no effect was observed on the incubation period of mouse prion disease. These results show that androgens influence the prion diseases incubation period after inoculation at a peripheral site.

Genotype-phenotype analysis in inherited prion disease with eight octapeptide repeat insertional mutation

“…This difference was more striking than in vCJD (which had a mean difference of 9.5 and 2 y, respectively). 24 The role of gender in prion diseases has otherwise yielded contradicting results, for instance females had longer survival in sporadic prion disease 19 but not in IPD with 8-OPRI as shown here. Similarly to IPD with 8-OPRIs, individuals affected by vCJD display both younger age of onset and longer disease duration when compared with 18 other than that denoted by * which was provided by personal communication also with Professor simon Mead. sCJD.…”

A Cell-Biased Effect of Estrogen in Prion Infection

“…In the same study, neither ovariectomy nor knockout of Er␣ affected the prion incubation period in female mice (12). However, parental female C57/BL6N mice were observed to have a shorter prion incubation period than their male counterparts (12). Female-specific prion-linked neuroprotection was reported in a study with Zrch I Prnp0/0 mice; in this study, ischemia insult led to high neuronal damage in the CA1 region, but only in the male mouse model (1).…”

“…The study by Loeuillet et al (12) supported a potential role for androgens in prion disease development when inoculation occurred at a peripheral site. In the same study, neither ovariectomy nor knockout of Er␣ affected the prion incubation period in female mice (12). However, parental female C57/BL6N mice were observed to have a shorter prion incubation period than their male counterparts (12).…”

“…In examining the potential role of Er␣ in prion disease development, Loeuillet et al (12) knocked out the Er␣ in C57/BL6N mice, but they saw no effect of Er␣ on prion disease development. As a result, we examined which of the Er receptors was responsible for the estrogen response seen here.…”

“…Studies have looked into the potential role of androgen receptors and Er␣ in prion disease development (12). Castration and androgen receptor deficiency in male C57/BL6N mice were found to prolong the incubation period of prion disease in animals intraperitoneally (i.p.)…”