Motherhood mitigates aging-related decrements in learning and memory and positively affects brain aging in the rat

Gatewood, Jessica; Morgan, Melissa; Eaton, Mollie; McNamara, Ilan; Stevens, Lillian Flores; Macbeth, Abbe H.; Meyer, Elizabeth; Lomas, Lisa M.; Kozub, Frederick J.; Lambert, Kelly G.; Kinsley, Craig Howard

doi:10.1016/j.brainresbull.2005.03.016

Cited by 138 publications

(143 citation statements)

References 41 publications

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“…In support, 3a,5a-THP has trophic effects to enhance central and peripheral myelination, it is neuroprotective in traumatic brain injury and ischemic stroke, and improves functional outcome after trauma (Magnaghi et al 2001, Schumacher et al 2001, Ghoumari et al 2003, Sayeed et al 2006, VanLandingham et al 2007). As such, trophic effects of 3a,5a-THP may underlie some of the neuroprotective aspects that have been reported with motherhood in aging (Gatewood et al 2005, Pawluski & Galea 2007. As well, we have previously found that the administration of 3a,5a-THP to OVX rats increases cognitive performance on the object placement task commensurate to P 4 administration alone (Frye et al 2007).…”

mentioning

confidence: 53%

“…3a,5a-THP is one such steroidogenic factor that is enhanced throughout pregnancy and has demonstrated neuroprotective and neuroproliferative effects , Djebaili et al 2005, Wang et al 2005, VanLandingham et al 2006, Leonelli et al 2007, Wang et al 2008. Of note, parity has been associated with reductions in age-related cognitive decrement and markers of neurodegeneration, as well as the increased expression of brain-derived neurotrophic factor (Gatewood et al 2005, Pawluski & Galea 2007, Macbeth et al 2008. Whether 3a,5a-THP may underlie some of the cognitive and/or trophic effects associated with reproductive experience has not been systematically investigated.…”

Section: Introductionmentioning

confidence: 99%

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Estrous cycle, pregnancy, and parity enhance performance of rats in object recognition or object placement tasks

Paris¹,

Frye²

2008

Reproduction

113

105

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Ovarian hormone elevations are associated with enhanced learning/memory. During behavioral estrus or pregnancy, progestins, such as progesterone (P 4 ) and its metabolite 5a-pregnan-3a-ol-20-one (3a,5a-THP), are elevated due, in part, to corpora luteal and placental secretion. During 'pseudopregnancy', the induction of corpora luteal functioning results in a hormonal milieu analogous to pregnancy, which ceases after about 12 days, due to the lack of placental formation. Multiparity is also associated with enhanced learning/memory, perhaps due to prior steroid exposure during pregnancy. Given evidence that progestins and/or parity may influence cognition, we investigated how natural alterations in the progestin milieu influence cognitive performance. In Experiment 1, virgin rats (nulliparous) or rats with two prior pregnancies (multiparous) were assessed on the object placement and recognition tasks, when in high-estrogen/P 4 (behavioral estrus) or low-estrogen/P 4 (diestrus) phases of the estrous cycle. In Experiment 2, primiparous or multiparous rats were tested in the object placement and recognition tasks when not pregnant, pseudopregnant, or pregnant (between gestational days (GDs) 6 and 12). In Experiment 3, pregnant primiparous or multiparous rats were assessed daily in the object placement or recognition tasks. Females in natural states associated with higher endogenous progestins (behavioral estrus, pregnancy, multiparity) outperformed rats in low progestin states (diestrus, non-pregnancy, nulliparity) on the object placement and recognition tasks. In earlier pregnancy, multiparous, compared with primiparous, rats had a lower corticosterone, but higher estrogen levels, concomitant with better object placement performance. From GD 13 until post partum, primiparous rats had higher 3a,5a-THP levels and improved object placement performance compared with multiparous rats.

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mentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Estrous cycle, pregnancy, and parity enhance performance of rats in object recognition or object placement tasks

Paris¹,

Frye²

2008

Reproduction

113

105

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“…There is evidence to suggest that beneficial effects of pregnancy on cognitive performance may persist beyond the gestational period. Water maze performance is better among multiparous than nulliparous rats (Gatewood et al, 2005). Multiparous rats have enhanced working memory performance and primiparous rats have enhanced reference memory performance compared to nulliparous rats which suggested that hormone-induced hippocampal modifications in pregnant rats may improve learning and memory ( (Kinsley et al 1999) albeit it is not clear whether some of these effects are due to motor or mnemonic processes).…”

Section: Discussionmentioning

confidence: 99%

Estrogens and progestins enhance spatial learning of intact and ovariectomized rats in the object placement task

Frye

Duffy

Walf

2007

Neurobiology of Learning and Memory

214

219

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Steroid modulation of cognitive function has focused on estrogen (E 2 ), but progestins naturally covary with E 2 and may also influence cognitive performance. Spatial performance in the object placement task over endogenous hormonal states in which E 2 and progestins vary, and when E 2 and/ or progestins were administered, was examined. Experiment 1: Rats in proestrus or estrus had significantly better performance in the object placement task than did diestrous rats. Experiment 2: Rats in the third trimester, post-partum, or lactation exhibited significantly better performance in the object placement task than did rats in the first trimester. Experiment 3: Ovariectomized (ovx) rats administered 17β-estradiol (0.9 mg/kg, subcutaneously (sc), progesterone (P; 4 mg/kg, sc), or E 2 and P, immediately after training in the object placement task, performed significantly better when tested 4 hours later, than did control rats administered vehicle (sesame oil 0.2 cc). Experiment 4: Ovx rats administered E 2 or P with a one and a half hour delay after training in the object placement task, did not perform differently than vehicle-administered controls. Experiment 5: Ovx rats administered post-training E 2 , which has a high affinity for both E 2 receptor (ER)α and β isoforms, or propyl pyrazole triol (PPT; 0.9 mg/kg, sc), which is more selective for ERα than ERβ, had significantly better performance in the object placement task than did rats administered vehicle or diarylpropionitrile (DPN; 0.9 mg/kg, sc), an ERβ selective ligand. Experiment 6: Ovx rats administered P, or its metabolite, 5α-pregnan-3α-ol-20-one (3α,5α-THP; 4 mg/kg, sc), immediately post-training performed significantly better in the object placement task than did vehicle control rats. Thus, performance in the object placement task is better when E 2 and/or P are naturally elevated or when E 2 , the ERα selective ER modulator PPT, P, or its metabolite, 3α,5α-THP, are administered post-training.

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“…Although the hormone surges are transient during pregnancy and the postpartum period, the effects of the changes induced by the reproductive experience on the brain's functions and behaviors are life-long (Kinsley et al 1999). For example, the emerging data indicate that the normal reproductive experience or motherhood can mitigate AAMI (Gatewood et al 2005) and alter the cellular response to estrogens in older hippocampi in rats (Barha and Galea 2011). These results suggest that the normal reproduction experience has a long-lasting and extensive influence on the AAMI in female rodents (Li et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Inflammatory insult during pregnancy accelerates age-related behavioral and neurobiochemical changes in CD-1 mice

Wang

Chen

et al. 2016

AGE

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Data shows that inflammation during pregnancy significantly exerts a long-term influence on offspring, such as increasing the risk of adult cognition decline in animals. However, it is unclear whether gestational inflammation affects the neurobehavioral and neurobiochemical outcomes in the motherself during aging. In this study, pregnant CD-1 mice intraperitoneally received lipopolysaccharide (LPS) in two doses (25 and 50 g/kg, respectively) or normal saline daily during gestational days 15-17. At the age of 15 months, a battery of behavioral tasks was employed to evaluate their species-typical behaviors, sensorimotor ability, anxiety levels, and spatial learning and memory abilities. An immunohistochemical method was utilized preliminarily to detect neurobiochemical indicators consisting of amyloid-β, p h o s p h o r y l a t e d t a u , p r e s y n a p t i c p r o t e i n s synaptotagmin-1 and syntaxin-1, glial fibrillary acidic protein (GFAP), and histone-4 acetylation on the K8 site (H4K8ac). The behavioral results showed that LPS exposure during pregnancy exacerbated a decline in 15-month-old CD-1 mice's abilities to nest, their sensorimotor and spatial learning and memory capabilities, and increased their anxiety levels. The neurobiochemical results indicated that gestational LPS exposure also intensified age-related hippocampal changes, including increased amyloid-β 42 , phosphorylated tau, synaptotagmin-1 and GFAP, and decreased syntaxin-1 and H4K8ac. Our results suggested that the inflammatory insult during pregnancy could be an important risk factor for the development of Alzheimer's disease, and the H4K8 acetylation might play an important role in the underlying mechanism. This study offers a perspective for improving strategies that support healthy development and successful aging.

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Motherhood mitigates aging-related decrements in learning and memory and positively affects brain aging in the rat

Cited by 138 publications

References 41 publications

Estrous cycle, pregnancy, and parity enhance performance of rats in object recognition or object placement tasks

Estrous cycle, pregnancy, and parity enhance performance of rats in object recognition or object placement tasks

Estrogens and progestins enhance spatial learning of intact and ovariectomized rats in the object placement task

Inflammatory insult during pregnancy accelerates age-related behavioral and neurobiochemical changes in CD-1 mice

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