Gene Expression Profiling in the Hippocampus of Orchidectomized Rats

Quintela, Telma; Marcelino, Helena; Gonçalves, Isabel; Patriarca, Filipa M.; Santos, Cecília R. A.

doi:10.1007/s12031-014-0304-9

Cited by 10 publications

(12 citation statements)

References 29 publications

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“…Multiple target proteins have been reported to be under regulation by androgens, such as the two enzymes important for converting testosterone into active metabolites (DHT and estradiol), 5α-reductase and aromatase (314), and the AR itself (324). A recent DNA microarray study compared gene expression in the hippocampus of castrated and sham-castrated males (507). Of the genes that were downregulated following castration, most were not only involved in intracellular signaling and cell survival, but also genes important for plasticity (507).…”

Section: Androgen Receptor Signalingmentioning

confidence: 99%

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Sex Hormones and Cognition: Neuroendocrine Influences on Memory and Learning

Hamson

Roes

Galea

2016

Comprehensive Physiology

173

110

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Sex differences in neurological disease exist in incidence, severity, progression, and symptoms and may ultimately influence treatment. Cognitive disturbances are frequent in neuropsychiatric disease with men showing greater cognitive impairment in schizophrenia, but women showing more severe dementia and cognitive decline with Alzheimer's disease. Although there are no overall differences in intelligence between the sexes, men, and women demonstrate slight but consistent differences in a number of cognitive domains. These include a male advantage, on average, in some types of spatial abilities and a female advantage on some measures of verbal fluency and memory. Sex differences in traits or behaviors generally indicate the involvement of sex hormones, such as androgens and estrogens. We review the literature on whether adult levels of testosterone and estradiol influence spatial ability in both males and females from rodent models to humans. We also include information on estrogens and their ability to modulate verbal memory in men and women. Estrone and progestins are common components of hormone therapies, and we also review the existing literature concerning their effects on cognition. We also review the sex differences in the hippocampus and prefrontal cortex as they relate to cognitive performance in both rodents and humans. There has been greater recognition in the scientific literature that it is important to study both sexes and also to analyze study findings with sex as a variable. Only by examining these sex differences can we progress to finding treatments that will improve the cognitive health of both men and women. © 2016 American Physiological Society. Compr Physiol 6:1295-1337, 2016.

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Section: Androgen Receptor Signalingmentioning

confidence: 99%

“…A recent DNA microarray study compared gene expression in the hippocampus of castrated and sham-castrated males (507). Of the genes that were downregulated following castration, most were not only involved in intracellular signaling and cell survival, but also genes important for plasticity (507).…”

Section: Androgen Receptor Signalingmentioning

confidence: 99%

Sex Hormones and Cognition: Neuroendocrine Influences on Memory and Learning

Hamson

Roes

Galea

2016

Comprehensive Physiology

173

110

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“…The modulation of androgens also alters the expression of neurotrophic factors and structural proteins associated with neuroplasticity in the hippocampus. Gonadectomised rats show reductions in genes associated with neurogenesis, neuroplasticity, and cell adhesion (Quintela et al, 2015). Conversely, 4-weeks of testosterone supplementation via silastic capsule in GDX male rats enhances the expression of the calcium-dependent cell adhesion molecule, Ncadherin, in the hippocampus (Monks et al, 2001).…”

Section: Hippocampal Neurogenesis and Androgensmentioning

confidence: 99%

Sex hormones and adult hippocampal neurogenesis: Regulation, implications, and potential mechanisms

Mahmoud

Wainwright

Galea

2016

Frontiers in Neuroendocrinology

169

110

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Neurogenesis within the adult hippocampus is modulated by endogenous and exogenous factors. Here, we review the role of sex hormones in the regulation of adult hippocampal neurogenesis in males and females. The review is framed around the potential functional implications of sex hormone regulation of adult hippocampal neurogenesis, with a focus on cognitive function and mood regulation, which may be related to sex differences in incidence and severity of dementia and depression. We present findings from preclinical studies of endogenous fluctuations in sex hormones relating to reproductive function and ageing, and from studies of exogenous hormone manipulations. In addition, we discuss the modulating roles of sex, age, and reproductive history on the relationship between sex hormones and neurogenesis. Because sex hormones have diverse targets in the central nervous system, we overview potential mechanisms through which sex hormones may influence hippocampal neurogenesis. Lastly, we advocate for a more systematic consideration of sex and sex hormones in studying the functional implications of adult hippocampal neurogenesis.

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“…Because steroids are hydrophobic, androgens pass directly through cell membranes to bind to cytoplasmic androgen receptors that dimerize and act as a transcription factors [166], and the resulting changes in gene transcription could explain the effects of androgens on neurogenesis. A comparison of the genes expressed within the hippocampus of intact and castrated male rats revealed 98 genes that were upregulated and 173 genes that were downregulated by castration [167]. The implications of these wide-ranging changes have not been well characterized, but it is noteworthy that NMDA receptors and GABA receptors were up-regulated in the hippocampus by castration [167], possibly compensating for reduced connectivity.…”

Section: Possible Molecular Pathways Within the Hippocampusmentioning

confidence: 99%

“…A comparison of the genes expressed within the hippocampus of intact and castrated male rats revealed 98 genes that were upregulated and 173 genes that were downregulated by castration [167]. The implications of these wide-ranging changes have not been well characterized, but it is noteworthy that NMDA receptors and GABA receptors were up-regulated in the hippocampus by castration [167], possibly compensating for reduced connectivity. Using a more focused approach, another study assessed changes in mRNA expression for specific genes involved in synaptic plasticity within the hippocampus of males rats within 9 days of castration [168].…”

Section: Possible Molecular Pathways Within the Hippocampusmentioning

confidence: 99%

Testosterone and Adult Neurogenesis

Spritzer

Roy

2020

Biomolecules

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It is now well established that neurogenesis occurs throughout adulthood in select brain regions, but the functional significance of adult neurogenesis remains unclear. There is considerable evidence that steroid hormones modulate various stages of adult neurogenesis, and this review provides a focused summary of the effects of testosterone on adult neurogenesis. Initial evidence came from field studies with birds and wild rodent populations. Subsequent experiments with laboratory rodents have tested the effects of testosterone and its steroid metabolites upon adult neurogenesis, as well as the functional consequences of induced changes in neurogenesis. These experiments have provided clear evidence that testosterone increases adult neurogenesis within the dentate gyrus region of the hippocampus through an androgen-dependent pathway. Most evidence indicates that androgens selectively enhance the survival of newly generated neurons, while having little effect on cell proliferation. Whether this is a result of androgens acting directly on receptors of new neurons remains unclear, and indirect routes involving brain-derived neurotrophic factor (BDNF) and glucocorticoids may be involved. In vitro experiments suggest that testosterone has broad-ranging neuroprotective effects, which will be briefly reviewed. A better understanding of the effects of testosterone upon adult neurogenesis could shed light on neurological diseases that show sex differences.

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Gene Expression Profiling in the Hippocampus of Orchidectomized Rats

Cited by 10 publications

References 29 publications

Sex Hormones and Cognition: Neuroendocrine Influences on Memory and Learning

Sex Hormones and Cognition: Neuroendocrine Influences on Memory and Learning

Sex hormones and adult hippocampal neurogenesis: Regulation, implications, and potential mechanisms

Testosterone and Adult Neurogenesis

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