The exposure to preeclamptic syndrome induces cognitive dysfunction and a depressive-like type phenotype in rats

Preeclampsia (PE) is a hypertensive pregnancy disorder that currently has no cure. Recent studies suggest an alarming trend that a subset of women with a history of PE often experience pronounced subjective cognitive and psychological dysfunction that significantly alters their quality of life; however, the mechanisms are unclear. We have reported impaired middle cerebral artery (MCA) resistance and elevated blood pressure (BP) in rats with PE at 2 months post-delivery. The goal of this study was to establish whether greater resistance of MCA is associated with cognitive dysfunction at 2 months after delivery. Transgenic rats were exposed to preeclamptic syndrome (TGA-PE: female TG for angiotensinogen mated to male TG for renin) and compared to Sprague-Dawley (SD) rats at 2-months post-delivery. Systolic and diastolic blood pressures (SBP, DBP) measured by a tail-cuff method (NIBP-8, Columbus Instruments) were elevated in TGA-PE vs. SD in at 2 months post-delivery (SBP: 150.1±1.6* vs. 116.2±3.1; DBP: 109.8±1.7* vs. 81.2±2.2, *p< 0.05, n=6). There were no differences in animals’ heart rate, body weight, or uterine weight among the strains (p>0.05, n=6). Next, rats were trained to respond on a touch-sensitive computer screen (Lafayette Instruments) whereby correct responses resulted in delivery of a single, 45-mg sucrose pellet. To assess associative learning, rats completed a pairwise discrimination task by learning to discriminate between two stimuli presented pseudo-randomly on the screen in daily cognition sessions. Compared to age-matched SD rats, TGA-PE rats required a greater number of sessions and total trials to acquire this pairwise discrimination task (>80 accuracy for 2 consecutive days). Moreover, only 4 of 6 TGA-PE rats acquired this task within 40 days. Importantly, the number of acquired sessions was positively correlated with systolic blood pressure in TGA-PE (R2: 0.9997, p< 0.0001) but not in SD (R2: 0.3149) rats. Consequently, the same rats responded on a progressive ratio schedule of reinforcement such that response requirements increased after each completed ratio to obtain each subsequent reward. While there were no differences in the number of reinforcers earned when 1 pellet served as the reinforcer (same reward magnitude as cognition study), TGA-PE rats did not increase responding when the reinforcer magnitude was increased to 3 pellets compared to SD rats. While further studies are warranted, these data imply that TGA-PE rats may have altered reward-related processing, consistent with an anhedonic-like type phenotype. Overall, our data demonstrate that exposure to preeclampsia results in impaired associative learning and anhedonic-like type phenotype in rats 2 months after delivery. Furthermore, hypertension and altered MCA hemodynamics may underlie the development of cognitive dysfunction following preeclampsia. Supported by NIH 1R01HL155420, R21 1R21HD114073. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.