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.

Estradiol reverses excitatory synapse loss in a cellular model of neuropsychiatric disorders

“…However, increasing evidence suggests that the beneficial effects of 17β-estradiol may also be in part conferred through the modulation of glutamatergic signaling 27,35,36 . This is supported by animal studies which show that 17β-estradiol enhances performance on a number of cognitive tasks, including attention and learning and memory tasks in healthy animals 27,28,54 as well as models of psychosis 30,[55][56][57] . Importantly, it is the ability of 17β-estradiol to modulate both glutamatergic and GABAergic systems that underlies these enhancing effects 45,48,[58][59][60][61] .…”

“…The neurosteroid, 17β-estradiol, has been shown to be a potent neuromodulator, having positive effects on cognitive processes including learning and memory as well as mood 27,28 . The effect of 17β-estradiol, the principal biologically active estrogen, on cognition is thought to be driven, in part, by activation of specific signaling pathways resulting in alternations in dendritic spine number and the trafficking of key synaptic proteins (reviewed in 13).…”

Neuroimmune Activation Drives Multiple Brain States

“…This is a particularly important avenue for research into individual differences and sex differences in susceptibility to immune-related disorders of cognition, memory and emotion (Perry et al, 2016; Snyder et al, 2016; Tronson and Collette, 2017; Choleris et al, 2018; Fisher et al, 2018; Speirs and Tronson, 2018). …”

Sex Differences in Age-related Impairments Vary across Cognitive and Physical Assessments in Rats

“…This includes increased cost associated with larger animal numbers, the erroneous perception of increased behavioral and physiological variability of females relative to males [5], as well as the lack of available females of certain rodent strains from common breeders, including the National Institute on Aging [6,7]. Despite these barriers, several key studies have documented differences in social behavior and behavioral outcomes, as well as the underlying molecular neurobiology across male and female rats (reviewed in [8]). Sex differences within the context of age-related cognitive and physical decline, however, remain largely under investigated.…”