Deletion of the Bax gene disrupts sexual behavior and modestly impairs motor function in mice

Abstract

Cell death is a nearly ubiquitous feature of the developing nervous system, and differential death in males and females contributes to several well studied sex differences in neuron number. Nonetheless, the functional importance of neuronal cell death has been subjected to few direct tests. Bax, a pro-apoptotic protein, is required for cell death in many neural regions. Deletion of the Bax gene in mice increases neuron number in several areas and eliminates sex differences in cell number in the brain and spinal cord. Here, sexual and motor behaviors were examined in Bax-/- mice and their wild-type siblings to test the functional consequences of preventing Bax-dependent cell death. Animals were gonadectomized in adulthood and provided with ovarian hormones or with testosterone for tests of feminine and masculine sexual behaviors, respectively. Wild-type mice exhibited a sex difference in feminine sexual behavior, with high lordosis scores in females and low scores in males. This sex difference was eliminated by Bax deletion, with very low receptivity exhibited by both male and female Bax-/- mice. Masculine sexual behavior was not sexually dimorphic among wild-type mice, but mounts and pelvic thrusts were nearly eliminated in Bax-/- mice of both sexes. Motor strength and performance at low speeds on a RotaRod apparatus did not differ by sex or Bax gene status. However, Bax-/- animals exhibited impairments on the RotaRod at higher speeds. Thus, developmental cell death may be required for masculine and feminine sexual behaviors and the fine tuning of motor coordination.

Dexamethasone induces apoptosis in the developing rat amygdala in an age-, region-, and sex-specific manner

“…It occurs through an intrinsic mechanism within the cell and is essential for the removal of damaged and superfluous cells (Pettmann and Henderson, 1998). Naturally occurring cell death occurs during the postnatal period within many brain regions including the amygdala, and inhibition or exacerbation of cell death can lead to later impairments in behavior (Jyotika et al, 2007; Broad et al, 2009; Rondi-Reig and Mariani, 2002). In the present study, the administration of DEX during both the late gestational and neonatal periods significantly increased apoptosis (as measured by cleaved caspase-3) within the amygdala.…”

Enhanced muscle fatigue occurs in male but not female ASIC3−/− mice

“…The Rota-Rod is commonly used to test coordination and motor performance in rodents at a gross level. To test motor performance, mice are run on a Rota-Rod for shorter durations (1-5 min) and at higher maximal speeds (up to 45 rpms) (7,10,35) than that used in the current study. Furthermore, in human subjects, fatigue affects coordination resulting in changes in firing patterns of muscles; however, there are no apparent gender differences in abilities to perform the exercise-related tasks (12,17).…”

Representing Sex in the Brain, One Module at a Time

“…It is likely therefore that females do not attack males because of a sexual dimorphism downstream of vomeronasal sensory input in the neural circuit that mediates aggression. Females of many species, including mice, exhibit low frequency male-pattern mating towards conspecific females (Baum et al, 1974; Beach, 1947; Jyotika et al, 2007; Kimchi et al, 2007; Spors and Sobel, 2007). This suggests that the neural circuit for masculine sexual behavior is present in both sexes, but it is normally inhibited by sensory input from the VNO (Figure 5A).…”