Progestogens’ effects and mechanisms for object recognition memory across the lifespan

Abstract

This review explores the effects of female reproductive hormones, estrogens and progestogens, with a focus on progesterone and allopregnanolone, on object memory. Progesterone and its metabolites, in particular allopregnanolone, exert various effects on both cognitive and non-mnemonic functions in females. The well-known object recognition task is a valuable experimental paradigm that can be used to determine the effects and mechanisms of progestogens for mnemonic effects across the lifespan, which will be discussed herein. In this task there is little test-decay when different objects are used as targets and baseline valance for objects is controlled. This allows repeated testing, within-subjects designs, and longitudinal assessments, which aid understanding of changes in hormonal milieu. Objects are not aversive or food-based, which are hormone-sensitive factors. This review focuses on published data from our laboratory, and others, using the object recognition task in rodents to assess the role and mechanisms of progestogens throughout the lifespan. Improvements in object recognition performance of rodents are often associated with higher hormone levels in the hippocampus and prefrontal cortex during natural cycles, with hormone replacement following ovariectomy in young animals, or with aging. The capacity for reversal of age- and reproductive senescence-related decline in cognitive performance, and changes in neural plasticity that may be dissociated from peripheral effects with such decline, are discussed. The focus here will be on the effects of brain-derived factors, such as the neurosteroid, allopregnanolone, and other hormones, for enhancing object recognition across the lifespan.

Pregnancy improves cognitive deficit and neuronal morphology atrophy in the prefrontal cortex and hippocampus of aging spontaneously hypertensive rats

“…Both hormones showed neuroprotective and neurotrophic properties (for review see Siddiqui et al, ). In agreement with our results, several reports in rats have demonstrated that memory assessed by the novel object recognition test (NORT) changes during the estrous cycle, pregnancy and the postpartum stage (for review see Hu, Yang, Gao, Rudd, & Fang, ; Walf, Koonce, & Frye, ). Interestingly, high scores in the NORT were reported in the diestrous stage of the estrus cycle and in the late pregnancy and 14‐day postpartum stage (middle step of the lactation period) (Paris & Frye, ; Walf et al, ).…”

“…In agreement with our results, several reports in rats have demonstrated that memory assessed by the novel object recognition test (NORT) changes during the estrous cycle, pregnancy and the postpartum stage (for review see Hu, Yang, Gao, Rudd, & Fang, ; Walf, Koonce, & Frye, ). Interestingly, high scores in the NORT were reported in the diestrous stage of the estrus cycle and in the late pregnancy and 14‐day postpartum stage (middle step of the lactation period) (Paris & Frye, ; Walf et al, ). Interestingly, a recent report (Zhu et al, ) in the animal model of chronic cerebral hypoperfusion, bilateral common carotid artery occlusion (BCCAO), suggest that the administration of 17‐β‐estradiol during 3 months ameliorated the cognitive deficits by enhancing the expression of ubiquitin, Aβ1–42, and pTau, these are synaptic proteins.…”

Emerging patterns of change for tomorrow’s cities

“…While it seems that digital structures also follow geographical laws (Hecht & Moxley 2009), urban research concerning human factors (Walf et al 2015, Henriques 2013, Zimring & Dalton 2003 is needed. Perhaps, common(s) language(s) such as maths, sounds, images, visual and textual programming might represent possible links within international and multicultural networks.…”

New Insights for Hormone Therapy in Perimenopausal Women Neuroprotection

“…The well-known object recognition task is a valuable experimental paradigm that can be used to determine the effects and mechanisms of progestogens for mnemonic effects across the lifespan. Improvements in object recognition performance of rodents are often associated with higher hormone levels in the hippocampus and prefrontal cortex during natural cycles, with progesterone replacement following ovariectomy in young animals, or with aging [54].…”

“…There were intensive efforts to develop progesterone neurobiology in the hippocampus and cortex, and current discoveries are sustaining P4 administration for more than uterine protection from endometrial hyperplasia and cancer, but for brain aging protection, besides the much analyzed "therapeutic window" of progesterone in brain trauma. P4 is active on cognition through its 5α-reduced metabolite, allopregnanolone [15,54], a fact that differentiates P4 from the progestin MPA, which proved as a jeopardizing drug for elder postmenopausal women. P4 has neuroprotective effects mediated by various mechanisms such as reduction of neuronal vulnerability to neurotoxic molecules, reduction of cell loss, inhibition of lipid peroxidation, and expression of pro-inflammatory genes [55][56][57].…”