Sex differences in the brain: Implications for behavioral and biomedical research

Abstract

Biological differences between males and females are found at multiple levels. However, females have too often been under-represented in behavioral neuroscience research, which has stymied the study of potential sex differences in neurobiology and behavior. This review focuses on the study of sex differences in the neurobiology of social behavior, memory, emotions, and recovery from brain injury, with particular emphasis on the role of estrogens in regulating forebrain function. This work, presented by the authors at the 2016 meeting of the International Behavioral Neuroscience Society, emphasizes varying approaches from several mammalian species in which sex differences have not only been documented, but also become the focus of efforts to understand the mechanistic basis underlying them. This information may provide readers with useful experimental tools to successfully address recently introduced regulations by granting agencies that either require (e.g. the National Institutes of Health in the United States and the Canadian Institutes of Health Research in Canada) or recommend (e.g. Horizon 2020 in Europe) the inclusion of both sexes in biomedical research.

Keywords: Cell death; Cerebral ischemia; Epigenetics; Estradiol; Hippocampus; Memory; Neurogenesis; Pattern separation; Social behavior; Stroke.

Figure 1

When males and females were compared in the intruder test of territorial aggression, males performed more attacks than females, which were reduced by castration (A). When dominance-related agonistic behaviors were included, no sex differences were found in total agonistic behaviors (B). Administration of ERα agonist PPT increased attacks in castrated males (C) and dominance aggression in ovariectomized (Ovx) females (D). The ERβ agonist WAY200070 instead only increased dominance in gonadally intact males (E) and overall agonistic behaviors (comprised mostly of dominance behavior) in females (F). * indicates a significant difference from the sesame oil treated control group at p < 0.05. ** = p < 0.01 in comparison to gonadally intact males. Modified from Clipperton-Allen et al. (2010, 2011).

Figure 2

Male and Female Sprague-Dawley adult rats were trained for 26 days on a delayed non-match to place version of the radial arm maze task with two patterns, with adjacent or separate arms as the correct choices. The sun symbol represents visual cues around the room (see C). A. Male spatial strategy users had a greater percentage of correct responses acquiring similar patters (adjacent arms) than all other groups. There were no sex differences in idiothetic strategy users or when acquiring distinct patterns (separate arms). B. Male strategy users had more new neurons in the dorsal dentate gyrus than all other groups. Asterisks indicates p < 0.05. Modified and reprinted with permission from Yagi et al. (2016).