Translational studies of estradiol and progesterone in fear and PTSD

Seligowski, Antonia V.; Hurly, Jordyn; Mellen, Emily; Ressler, Kerry J.; Ramikie, Teniel S.

doi:10.1080/20008198.2020.1723857

Cited by 18 publications

(16 citation statements)

References 58 publications

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“…They found that women with PTSD had a deficit in the synthesis of those metabolites, suggesting that lower amounts of progesterone metabolites and not high progesterone per se, explain the findings related to poor extinction retention in PTSD [62]. For a comprehensive summary of studies on estradiol and progesterone in fear and PTSD, please refer to recent reviews [16,63]. In summary, although there has been limited focus on the role of progesterone and testosterone in fear memory processes compared to estradiol research, available evidence points to lower levels of estradiol and progesterone metabolites in the pathogenesis of PTSD.…”

Section: Sex Differences In Neuroendocrine Axismentioning

confidence: 99%

Sex differences in post-traumatic stress disorder risk: autonomic control and inflammation

2020

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Aim: Over 7 million U.S. adults and about 20% of the military population have post-traumatic stress disorder (PTSD), a debilitating condition that is independently linked to a significantly greater risk of developing cardiovascular disease (CVD). Women have twice the probability of developing PTSD after experiencing a traumatic event compared to men. Existing literatures have reported higher inflammation and autonomic dysfunction including impaired baroreflex sensitivity, increased sympathetic reactivity and decreased parasympathetic activity in PTSD. However, most of these findings stem from studies conducted predominantly in males. Methods:We attempt in this narrative review to summarize the mixed literature available on sex differences in autonomic dysfunction and inflammation in PTSD, at rest and in response to stress in PTSD.Results: This review reveals that there is a paucity of research exploring autonomic function in females with PTSD. Recent studies have included female participants without probing for sex differences. A small number of studies have been conducted exclusively in women. Available data Terms of use and reuse: academic research for non-commercial purposes, see here for full terms. https://www.springer.com/aamterms-v1

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Section: Sex Differences In Neuroendocrine Axismentioning

confidence: 99%

Sex differences in post-traumatic stress disorder risk: autonomic control and inflammation

2020

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“…This technology could generalize beyond the HPA axis. Sex hormones such as estrogen, progesterone, and testosterone all affect learning processes (32,33,45–47) and are broadly implicated in psychiatrically relevant functions (6,48,50). Systemic administration of these hormones in animal studies relies on subcutaneous or intraperitoneal injections, which can be stressful and interfere with the sex hormone effects being investigated.…”

Section: Discussionmentioning

confidence: 99%

Probing Neuro-Endocrine Interactions Through Wireless Magnetothermal Stimulation of Peripheral Organs

Maeng

Rosenfeld

Simandl

et al. 2021

Preprint

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Exposure to stress alters hypothalamic-pituitary-adrenal (HPA) axis reactivity; however, it is unclear exactly how or where within the HPA pathway these changes occur. Dissecting these mechanisms requires tools to reliably probe HPA function, particularly the adrenal component, with temporal precision. We previously demonstrated magnetic nanoparticle (MNP) technology to remotely trigger adrenal hormone release by activating thermally sensitive ion channels. Here, we applied adrenal magnetothermal stimulation to probe stress-induced HPA axis changes. MNP and control nanoparticles were injected into the adrenal glands of outbred rats subjected to a tone-shock conditioning/extinction/recall paradigm. We measured MNP-triggered adrenal release before and after conditioning through physiologic (heart rate) and serum (epinephrine, corticosterone) markers. Aversive conditioning altered adrenal function, reducing corticosterone and blunting heart rate increases post-conditioning. MNP-based organ stimulation provides a novel approach to probing the function of HPA and other neuro-endocrine axes and could help elucidate changes across stress and disease models.

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“…In contrast to testosterone, plasma levels of estradiol were not affected by trauma. It remains to be established whether estradiol plays a role in PTSD symptomatology or whether the progesterone/estradiol ratio may be essential for understating sex-dependent differences in fear and PTSD ( Seligowski et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Sex, Pramipexole and Tiagabine Affect Behavioral and Hormonal Response to Traumatic Stress in a Mouse Model of PTSD

et al. 2021

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Posttraumatic stress disorder (PTSD) has been associated with abnormal regulation of the hypothalamic-pituitary-adrenal gland axis (HPA). Women demonstrate a more robust HPA response and are twice as likely to develop PTSD than men. The role of sex hormones in PTSD remains unclear. We investigated whether post-trauma chronic treatment with the GABA-ergic agent tiagabine and dopamine-mimetic pramipexole affected the behavioral outcome and plasma levels of corticosterone, testosterone, or 17β-estradiol in female and male mice. These medications were investigated due to their potential capacity to restore GABA-ergic and dopaminergic deficits in PTSD. Animals were exposed to a single prolonged stress procedure (mSPS). Following 13 days treatment with tiagabine (10 mg/kg) or pramipexole (1 mg/kg) once daily, the PTSD-like phenotype was examined in the fear conditioning paradigm. Plasma hormones were measured almost immediately following the conditioned fear assessment. We report that the exposure to mSPS equally enhanced conditioned fear in both sexes. However, while males demonstrated decreased plasma corticosterone, its increase was observed in females. Trauma elevated plasma testosterone in both sexes, but it had no significant effects on 17β-estradiol. Behavioral manifestation of trauma was reduced by pramipexole in both sexes and by tiagabine in females only. While neither compound affected corticosterone in stressed animals, testosterone levels were further enhanced by tiagabine in females. This study shows sex-dependent efficacy of tiagabine but not pramipexole in a mouse model of PTSD-like symptoms and a failure of steroid hormones’ levels to predict PTSD treatment efficacy.

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Translational studies of estradiol and progesterone in fear and PTSD

Cited by 18 publications

References 58 publications

Sex differences in post-traumatic stress disorder risk: autonomic control and inflammation

Sex differences in post-traumatic stress disorder risk: autonomic control and inflammation

Probing Neuro-Endocrine Interactions Through Wireless Magnetothermal Stimulation of Peripheral Organs

Sex, Pramipexole and Tiagabine Affect Behavioral and Hormonal Response to Traumatic Stress in a Mouse Model of PTSD

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