Pubertal ovarian hormone exposure reduces the number of myelinated axons in the splenium of the rat corpus callosum

Abstract

The size of the female rat corpus callosum decreases in response to pubertal ovarian hormone exposure, but the underlying changes in axonal composition have not been examined. In the current study, animals underwent ovariectomy or sham surgery at day 20, and the number of myelinated and unmyelinated axons were examined in young adulthood (2 mo.) using electron microscopy. Ovariectomized animals had a greater number of myelinated axons compared to intact animals, while total axon number was not affected. Ovarian hormone exposure seems to limit the number of axons that become myelinated in the splenium, while not affecting the number of axons crossing through the region. Keywordsestrogen; progesterone; myelin; oligdodendrocyte; adolescence; corticosteroids The corpus callosum is sexually dimorphic in the rat, with males having a larger total corpus callosum size than females (Berrebi et al, 1988;Fitch et al, 1991;Bimonte et al., 2000a;2000b;2000c;Denenberg et al., 1991). The splenium, defined as the posterior 20% of the total callosal length, carries axons from the visual cortex (Kim et al., 1996). Sex differences in the size of the splenium (Nunez and Juraska, 1998) are due to a greater number of myelinated axons within the splenium of males though there are no differences in total axon number (Kim et al., 1996). Differences in myelinated axon number are established by young adulthood (day 60), but are not seen in prepubertal animals examined at 25 days of age (Kim and Juraska, 1997). On the other hand, females have more total axons at day 25. However, because of continued axon elimination in females this difference is abolished by day 60 (Kim and Juraska, 1997). Thus, the onset of puberty around day 35 may affect both myelination and axon withdrawal.Prepubertal ovariectomy (OVX) at day 25 has been shown to increase the overall size of the corpus callosum in adulthood (Bimonte et al., 2000a(Bimonte et al., , 2000b(Bimonte et al., , 2000c, while OVX at day 70 is without effect (Bimonte et al, 2000c). The underlying structural changes responsible for this increase in size have not been examined. It is possible that the removal of ovarian hormones before puberty reduces axon elimination or increases the number of axons that get myelinated, resulting in a greater callosal size. In the primary visual cortex, which projects axons through Corresponding author: Janice M. Juraska, Ph.D., Department of Psychology, 603 E. Daniel St., Champaign, IL 61820, (217) 333-8546, Fax: (217) 244-5876, jjuraska@cyrus.psych.uiuc.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Pu...

The timing of neuronal loss across adolescence in the medial prefrontal cortex of male and female rats

“…In females, there was no increase in white matter volume between P35 and P45, corresponding with puberty. Ovariectomy prior to puberty resulted in increased volume of white matter under the mPFC in adult females (Koss et al, 2014), extending the finding of Yates and Juraska (2008) that pubertal ovarian hormones slow the progression of myelination during adolescence in the posterior corpus callosum. Furthermore, in humans, while testosterone is positively correlated with white matter development, estradiol levels are negatively correlated with the size of frontal white matter in adolescent girls (Herting et al, 2012).…”

“…Electron microscopic analysis of the posterior (splenium) corpus callosum shows that there is an increase in the number of axons that are myelinated between the juvenile period and adulthood, even while axons are pruned (Kim & Juraska, 1997). Furthermore the presence of ovarian hormones from puberty on leads to a lower number of myelinated axons in this region in early adulthood (Yates & Juraska, 2008). Like the posterior corpus callosum, the volume of the white matter under the prefrontal cortex continues to increase between adolescence and adulthood in both male and female rats.…”

Cerebral white matter in early puberty is associated with luteinizing hormone concentrations

“…Alternatively, the observed effect of LH might be an indirect result of sex steroids, as sex steroids are the end-products of the HPGaxis. Indeed, myelination of axons in the splenium is affected by manipulating levels of estrogen as demonstrated in pubertal rats (Yates and Juraska, 2008). Consequently, we are not able to exclude the contribution of other (sex steroid) hormones to the association between LH and white matter structure.…”

“…LH, together with the gonadotropin follicle stimulating hormone (FSH), stimulates the production of sex steroids which leads to the production of testosterone in boys and estrogens in girls. From animal studies, it has been established that sex steroids have organizational properties onto the brain that include neurogenesis and neurite outgrowth (McEwen and Alves, 1999), myelination of axons (Yates and Juraska, 2008) and growth of astrocytic processes in white matter (Chowen et al, 2000). In adult humans, pharmacologically induced changes in the levels of testosterone and estrogens have been shown to alter total brain and hypothalamus volumes (Hulshoff Pol et al, 2006a).…”

The development of psychotic disorders in adolescence: A potential role for hormones

“…Extensive experimental animal research suggests that adrenal and gonadal hormonal changes affect brain organization during adolescence (Cashion et al, 2003; Schulz et al, 2009; Sisk and Zehr, 2005; Vigil et al, 2011; Yates and Juraska, 2008). More recently, studies of human subjects have yielded findings suggesting similar effects.…”