Sex differences in mechanisms of disease

Shansky, Rebecca M.

doi:10.1111/gbb.12646

Cited by 13 publications

(9 citation statements)

References 12 publications

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“…HUA is just one of many conditions that have observable sex differences, as differing pathologies based on sex have been observed in a variety of fields [14][15][16][17] including cardiovascular [18][19][20][21], neurological [22][23][24][25], immunological [26][27][28], and renal diseases [29][30][31][32][33]. The architecture of the female kidney is likely distinct from that of the male kidney [34], given women have a lower blood pressure than men [35], women are less likely to develop acute kidney injury than men [36,37], women demonstrate improved tolerance to renal ischemia [38,39], and women are protected from renal and cardiovascular disease before menopause as compared to men [40,41].…”

Section: Urate As a Risk Factor In Diseasementioning

confidence: 99%

Sex Differences in Urate Handling

Kuhns

Woodward

2020

IJMS

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Hyperuricemia, or elevated serum urate, causes urate kidney stones and gout and also increases the incidence of many other conditions including renal disease, cardiovascular disease, and metabolic syndrome. As we gain mechanistic insight into how urate contributes to human disease, a clear sex difference has emerged in the physiological regulation of urate homeostasis. This review summarizes our current understanding of urate as a disease risk factor and how being of the female sex appears protective. Further, we review the mechanisms of renal handling of urate and the significant contributions from powerful genome-wide association studies of serum urate. We also explore the role of sex in the regulation of specific renal urate transporters and the power of new animal models of hyperuricemia to inform on the role of sex and hyperuricemia in disease pathogenesis. Finally, we advocate the use of sex differences in urate handling as a potent tool in gaining a further understanding of physiological regulation of urate homeostasis and for presenting new avenues for treating the constellation of urate related pathologies.

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Section: Urate As a Risk Factor In Diseasementioning

confidence: 99%

Sex Differences in Urate Handling

Kuhns

Woodward

2020

IJMS

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“…As we've shown in prior studies (Javadi-Paydar et al, 2019b;Javadi-Paydar et al, 2018a;Nguyen et al, 2016a;Nguyen et al, 2016b), this can be effected with changes in drug concentration in the vapor vehicle and the duration of exposure, thus these parameters were under investigation. The final goal was to determine if there are any substantive sex differences in the response to heroin inhalation, see Craft (Craft, 2008) for review, consistent with current suggestions for the inclusion of both male and female subjects in research where possible (Clayton and Collins, 2014;Shansky, 2020;Shansky and Woolley, 2016). While male and female rats acquire intravenous oxycodone self-administration at similar rates with 1-h access sessions (Mavrikaki et al, 2017), our recent study with 8-h access found that female rats self-administered more oxycodone in acquisition, but did not reach higher breakpoints in a PR dose-substitution (Nguyen et al, 2020b).…”

Section: Introductionmentioning

confidence: 99%

A vapor exposure method for delivering heroin alters nociception, body temperature and spontaneous activity in female and male rats

Gutierrez

Creehan

Taffe

2021

Journal of Neuroscience Methods

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Background:The ongoing crisis related to non-medical use of opioids makes it of continued importance to understand the risk factors for opioid addiction, the behavioral and neurobiological consequences of opioid exposure and to seek potential avenues for therapy.Pre-clinical rodent models have been critical to advancing understanding of opioid consequences for decades, but have been mostly limited to drug delivery by injection or by oral dosing. Inhalation, a significant route for many human users, has not been as well-established. Method:We adapted an e-cigarette based exposure system, previously shown efficacious for delivery of other drugs to rats, to deliver heroin vapor. Effects in vivo were assessed in male and female Sprague-Dawley rats using a warm-water assay for anti-nociception and an implanted radiotelemetry system for evaluating changes in body temperature and spontaneous activity rate.Results: Inhalation of vapor created by heroin 100 mg/mL in the propylene glycol (PG) vehicle significantly slowed tail-withdrawal from a 52°C water bath, bi-phasically altered activity, and increased temperature in male and female rats. Inhalation of heroin 50 mg/mL for 15 minutes produced significant effects, as the lower bound on efficacy, whereas inhalation of heroin 100 mg/mL for 30 minutes produced robust effects across all endpoints and groups. Conclusions:This work shows that e-cigarette devices deliver psychoactive doses of heroin to rats, using concentrations of ~50-100 mg/mL and inhalation durations of 15-30 minutes. This technique may be useful to assess the health consequences of inhaled heroin and other opioid drugs.

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“…Specifically, much of the pre-clinical work above has been conducted in male rodents, with very little focus on females. Others have eloquently expressed elsewhere (Shansky, 2018(Shansky, , 2019(Shansky, , 2020 the importance of: (a) investigating females as a stand-alone research question, as opposed to only in contrast to males as a baseline; and (b) the unlikeliness that female rodents have more behavioral and neurobiological variability, or that this variability is due to female-dominant sex hormones. Also, standard operating procedures may help to rectify some of the discrepancies seen.…”

Section: Discussionmentioning

confidence: 99%

Turning the ′Tides on Neuropsychiatric Diseases: The Role of Peptides in the Prefrontal Cortex

Brockway

Crowley

2020

Front. Behav. Neurosci.

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Recent advancements in technology have enabled researchers to probe the brain with the greater region, cell, and receptor specificity. These developments have allowed for a more thorough understanding of how regulation of the neurophysiology within a region is essential for maintaining healthy brain function. Stress has been shown to alter the prefrontal cortex (PFC) functioning, and evidence links functional impairments in PFC brain activity with neuropsychiatric disorders. Moreover, a growing body of literature highlights the importance of neuropeptides in the PFC to modulate neural signaling and to influence behavior. The converging evidence outlined in this review indicates that neuropeptides in the PFC are specifically impacted by stress, and are found to be dysregulated in numerous stress-related neuropsychiatric disorders including substance use disorder, major depressive disorder (MDD), posttraumatic stress disorder, and schizophrenia. This review explores how neuropeptides in the PFC function to regulate the neural activity, and how genetic and environmental factors, such as stress, lead to dysregulation in neuropeptide systems, which may ultimately contribute to the pathology of neuropsychiatric diseases.

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Sex differences in mechanisms of disease

Cited by 13 publications

References 12 publications

Sex Differences in Urate Handling

Sex Differences in Urate Handling

A vapor exposure method for delivering heroin alters nociception, body temperature and spontaneous activity in female and male rats

Turning the ′Tides on Neuropsychiatric Diseases: The Role of Peptides in the Prefrontal Cortex

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