Gynecological surgery in adulthood imparts cognitive and brain changes in rats: A focus on hysterectomy at short-, moderate-, and long-term intervals after surgery

Stephanie V. Koebele, Victoria E. Bernaud, Steven N. Northup-Smith, Mari N. Willeman, Isabel M. Strouse, Haidyn L. Bulen, Ally R. Schrier, Jason M. Newbern, Dale F. DeNardo, Loretta P. Mayer, Cheryl A. Dyer, Heather A. Bimonte‐Nelson
In: Hormones and Behavior · 2023 · vol. 155 , pp. 105411 · doi:10.1016/j.yhbeh.2023.105411 · PMID:37659358 · W4386316688
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Gynecological surgery in adult rats, specifically hysterectomy, induced significant cognitive deficits and altered brain structure at short-, moderate-, and long-term intervals post-surgery.

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Abstract

Premenopausal hysterectomy is associated with a greater relative risk of dementia. We previously demonstrated cognitive impairments in adult rats six weeks after hysterectomy with ovarian conservation compared with intact sham-controls and other gynecological surgery variations. Here, we investigated whether hysterectomy-induced cognitive impairments are transient or persistent. Adult rats received sham-control, ovariectomy (Ovx), hysterectomy, or Ovx-hysterectomy surgery. Spatial working memory, reference memory, and anxiety-like behavior were tested either six-weeks post-surgery, in adulthood; seven-months post-surgery, in early middle-age; or twelve-months post-surgery, in late middle-age. Hysterectomy in adulthood yielded spatial working memory deficits at short-, moderate-, and long-term post-surgery intervals. Serum hormone levels did not differ between ovary-intact, but differed from Ovx, groups. Hysterectomy had no significant impact on healthy ovarian follicle or corpora lutea counts for any post-surgery timepoint compared with intact sham-controls. Frontal cortex, dorsal hippocampus, and entorhinal cortex were assessed for activity-dependent markers. In entorhinal cortex, there were alterations in FOSB and ΔFOSB expression during the early middle-age timepoint, and phosphorylated ERK1/2 levels at the adult timepoint. Collectively, results suggest a primary role for the uterus in regulating cognition, and that memory-related neural pathways may be modified following gynecological surgery. This is the first preclinical report of long-term effects of hysterectomy with and without ovarian conservation on cognition, endocrine, ovarian, and brain assessments, initiating a comprehensive framework of gynecological surgery effects. Translationally, findings underscore critical needs to decipher how gynecological surgeries, especially those involving the uterus, impact the brain and its functions, the ovaries, and overall aging from a systems perspective.

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organisms 18
rattus sp. rattus sp. rattus sp. humans rodents microbiota zitter rats rattus sp. zin50786 multicellular animals human transgenic mice papio papio sensu groves wild boar spilosoma lutea rabbits homo heidelbergensis noordeloos 2009062
chemicals 22
water isoflurane oxygen meloxicam buprenorphine bupivacaine ethanol 6beta-[n-(carboxymethylamino)carbonyl]methoxy-17beta-estradiol progesterone estradiol chloramine t polystyrene polymer peptide haematoxylin triton sodium deoxycholate bis-tris polyboron hydride peroxide estrogen steroid

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