Androgens Are Neuroprotective in the Dentate Gyrus of Adrenalectomized Female Rats

Frye, Cheryl A.; McCormick, Cheryl M.

doi:10.3109/10253890009001122

Cited by 42 publications

(22 citation statements)

References 50 publications

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“…In adults, both androgens and estrogens have been shown to be neuroprotective in the hippocampus following adrenalectomy or kainic acid administration (Frye 2001; Frye and McCormick, 2000a,b; Veiga et al, 2003). Testicular surges of testosterone occur during the prenatal and early neonatal periods and these may inhibit the effects of DEX on apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Dexamethasone induces apoptosis in the developing rat amygdala in an age-, region-, and sex-specific manner

et al. 2011

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Exposure to glucocorticoids (GCs) in early development can lead to long-term changes in brain function and behavior although little is known about the underlying neural mechanisms. Perinatal exposure to GCs alters adult anxiety and neuroendocrine responses to stress. Therefore, we investigated the effects of either late gestational or neonatal exposure to the GC receptor agonist dexamethasone (DEX), on apoptosis within the amygdala, a region critical for emotional regulation. DEX was administered to timed-pregnant rat dams from gestational day 18 until parturition, or postnatal day 4-6. Offspring were sacrificed the day following the last DEX treatment and tissue was processed for immunohistochemical detection of cleaved caspase-3, a marker for apoptotic cells. Prenatal DEX treatment significantly increased the number of cleaved caspase-3 positive cells in the amygdala of both sexes, largely due to increases within the medial and basomedial sub-regions. Postnatal DEX treatment also increased cleaved caspase-3 immunoreactivity within the amygdala, although effects reached significance only in the central nucleus of females. Overall, DEX induction of cleaved caspase-3 in the amygdala was greater following prenatal compared to postnatal treatment, yet in both instances elevations in cleaved caspase-3 correlated with an increase in pro-apoptotic Bax mRNA expression. Dual-label immunohistochemistry of cleaved caspase-3 and the neuronal marker NeuN confirmed that virtually all cleaved caspase-3 positive cells in the amygdala were neurons and a subset of these cells (primarily following postnatal treatment) expressed a GABAergic calcium binding protein phenotype (calbindin or calretinin). Together these results indicate that early developmental GC exposure induces neuronal apoptosis within the amygdala in an age, sex, and region dependent manner.

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Section: Discussionmentioning

confidence: 99%

Dexamethasone induces apoptosis in the developing rat amygdala in an age-, region-, and sex-specific manner

et al. 2011

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“…In seizure-related lesion paradigms similar to our kainate model, Frye and colleagues found that acute androgen treatment reduced hippocampal damage (Frye and McCormick, 2000;Frye and Reed, 1998). Their data suggests a protective mechanism that involves inhibition of seizure activity by the DHT metabolite 5α-androstane-3α, 17β-diol (3α-diol) (Rhodes and Frye, 2004;.…”

Section: Androgens Regulate Neuron Viabilitymentioning

confidence: 96%

Androgen cell signaling pathways involved in neuroprotective actions

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Nguyen

Ramsden

et al. 2008

Hormones and Behavior

116

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As a normal consequence of aging in men, testosterone levels significantly decline in both serum and brain. Age-related testosterone depletion results in increased risk of dysfunction and disease in androgen-responsive tissues, including brain. Recent evidence indicates that one deleterious effect of age-related testosterone loss in men is increased risk for Alzheimer's disease (AD). We discuss recent findings from our laboratory and others that identify androgen actions implicated in protecting the brain against neurodegenerative diseases and begin to define androgen cell signaling pathways that underlie these protective effects. Specifically, we focus on the roles of androgens as (1) endogenous negative regulators of β-amyloid accumulation, a key event in AD pathogenesis, and (2) neuroprotective factors that utilize rapid non-genomic signaling to inhibit neuronal apoptosis. Continued elucidation of cell signaling pathways that contribute to protective actions of androgens should facilitate the development of targeted therapeutic strategies to combat AD and other agerelated neurodegenerative diseases.

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“…Early corticosterone exposure is necessary for dentate gyrus development of rodents and species-typical cognitive function (He et al, 2009) and glucocorticoid production from the adrenals promotes cell survival in the brain. Indeed, removal of the adrenals in rats increases cell death in the granule layer and dentate gyrus of the hippocampus (Frye and McCormick, 2000a,b; Rhodes et al, 2004). Moreover, co-administration of the 5α-reductase inhibitor, finasteride, with P 4 reinstatement attenuates these effects in ovariectomized females (Rhodes et al, 2004), suggesting that adrenally derived, 5α-reduced progestogens have important trophic effects to maintain limbic integrity.…”

Section: Neurodevelopmental Neuropsychiatric and Neurodegenerative mentioning

confidence: 99%

Prenatal Stress Alters Progestogens to Mediate Susceptibility to Sex-Typical, Stress-Sensitive Disorders, such as Drug Abuse: A Review

et al. 2011

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Maternal–offspring interactions begin prior to birth. Experiences of the mother during gestation play a powerful role in determining the developmental programming of the central nervous system. In particular, stress during gestation alters developmental programming of the offspring resulting in susceptibility to sex-typical and stress-sensitive neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. However, neither these effects, nor the underlying mechanisms, are well understood. Our hypothesis is that allopregnanolone, during gestation, plays a particularly vital role in mitigating effects of stress on the developing fetus and may mediate, in part, alterations apparent throughout the lifespan. Specifically, altered balance between glucocorticoids and progestogens during critical periods of development (stemming from psychological, immunological, and/or endocrinological stressors during gestation) may permanently influence behavior, brain morphology, and/or neuroendocrine-sensitive processes. 5α-reduced progestogens are integral in the developmental programming of sex-typical, stress-sensitive, and/or disorder-relevant phenotypes. Prenatal stress (PNS) may alter these responses and dysregulate allopregnanolone and its normative effects on stress axis function. As an example of a neurodevelopmental, neuropsychiatric, and/or neurodegenerative process, this review focuses on responsiveness to drugs of abuse, which is sensitive to PNS and progestogen milieu. This review explores the notion that allopregnanolone may effect, or be influenced by, PNS, with consequences for neurodevelopmental-, neuropsychiatric-, and/or neurodegenerative- relevant processes, such as addiction.

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Androgens Are Neuroprotective in the Dentate Gyrus of Adrenalectomized Female Rats

Cited by 42 publications

References 50 publications

Dexamethasone induces apoptosis in the developing rat amygdala in an age-, region-, and sex-specific manner

Dexamethasone induces apoptosis in the developing rat amygdala in an age-, region-, and sex-specific manner

Androgen cell signaling pathways involved in neuroprotective actions

Prenatal Stress Alters Progestogens to Mediate Susceptibility to Sex-Typical, Stress-Sensitive Disorders, such as Drug Abuse: A Review

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