Solving for (se)x

ity is induced in rodents either by peripheral nerve injury or inflammation, and it is thought to model chronic pain in humans. Studies with male mice show that hypersensitivity induced by peripheral nerve injury involves microglia, the immune cells of the central nervous system. In their study, however, Mogil and colleagues showed that such injury-induced pain hypersensitivity in females does not involve microglia, but instead involves cells of the adaptive immune system. This study could inform the treatment of chronic pain in humans, and the use of drugs that target microglia for that purpose. Responses to stress also differ between males and females. Indeed, such differences between men and women are thought to contribute to the different prevalence of various psychiatric diseases in the two populations. Tracy Bale (University of Pennsylvania) and colleagues have recently shown that a stress hormone differentially affects the activity of neurons in the brains of male and female mice8. The authors studied neurons in an area of the brain, the dorsal raphe, which produce the neurotransmitter serotonin. Serotonin is involved in regulating stress response and mood, among other functions, and is affected by some common antidepressant drugs. cycle causes increased variability in female models. In mice, for example, the estrous cycle consists of 4 phases spanning 4 days. A common concern is that female mice will show large differences in measured data depending on where they are in this cycle, whereas males are believed to be more consistent from day to day. As a result, many researchers believe that studying female mice necessitates monitoring where they are in their estrous cycle (a time-consuming process) and increasing sample sizes 4-fold to compensate for increased variability. However, a recent meta-analysis showed that there is no more variability in female mice than in males5. Irving Zucker (University of California, Berkeley, CA) and colleagues analyzed 293 articles published during 2009–2012. These studies examined behavioral, morphological, physiological and molecular traits both in male mice and in female mice across the estrous cycle. They found that variability amongst individuals was no greater in female mice than in males, and in fact, it was greater for some traits in males. These findings suggest that researchers do not need to monitor the estrous cycle in studies involving female mice, nor are larger numbers of female mice necessary to achieve the same statistical power seen in studies of male mice.

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[3]  Simon C Watkins,et al.  Innate Gender-based Proclivity in Response to Cytotoxicity and Programmed Cell Death Pathway* , 2004, Journal of Biological Chemistry.

[4]  I. Zucker,et al.  Female mice liberated for inclusion in neuroscience and biomedical research , 2014, Neuroscience & Biobehavioral Reviews.

[5]  V. Cuomo,et al.  Gender differences in drug responses. , 2007, Pharmacological research.

[6]  J. Mogil,et al.  Sex differences in pain and pain inhibition: multiple explanations of a controversial phenomenon , 2012, Nature Reviews Neuroscience.

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[8]  Loren J. Martin,et al.  Different immune cells mediate mechanical pain hypersensitivity in male and female mice , 2015, Nature Neuroscience.

[9]  B. Walker,et al.  Estrogens protect male mice from obesity complications and influence glucocorticoid metabolism , 2015, International Journal of Obesity.

[10]  R. Voskuhl,et al.  Estrogen receptor‐β ligand treatment after disease onset is neuroprotective in the multiple sclerosis model , 2013, Journal of neuroscience research.

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[12]  M. Sikorska,et al.  Sex of the cell dictates its response: differential gene expression and sensitivity to cell death inducing stress in male and female cells , 2009, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[13]  Alon Chen,et al.  Sex Differences in Corticotropin-Releasing Factor Receptor-1 Action Within the Dorsal Raphe Nucleus in Stress Responsivity , 2014, Biological Psychiatry.

[14]  R. Rubin,et al.  A role for cell sex in stem cell–mediated skeletal muscle regeneration: female cells have higher muscle regeneration efficiency , 2007, The Journal of cell biology.