Cell death and sexual differentiation of the nervous system

Forger, N.G.

doi:10.1016/j.neuroscience.2005.07.006

Cited by 143 publications

(98 citation statements)

References 69 publications

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“…In general terms, these findings thus show that both the volume and distribution of cells are shifted from the rostral to caudal direction in females relative to males. Although evidence for sex differences in the total volume of various nuclei in the CNS is relatively well documented (Forger, 2006), we believe that this is the first demonstration of a sex difference in the 3D cytoarchitecture of the midbrain DA systems. It remains to be determined whether sex steroid hormones play an important role in determining these differences, as they do in other nuclei (Simerly, 2005;Forger, 2006).…”

Section: Gc Programming Of Midbrain Da Cytoarchitecturementioning

confidence: 60%

“…Although evidence for sex differences in the total volume of various nuclei in the CNS is relatively well documented (Forger, 2006), we believe that this is the first demonstration of a sex difference in the 3D cytoarchitecture of the midbrain DA systems. It remains to be determined whether sex steroid hormones play an important role in determining these differences, as they do in other nuclei (Simerly, 2005;Forger, 2006). However, there are clear sex differences in the behavioral, neurochemical, and neurodegenerative responses within the NSDA pathway (Becker, 1999;Murray et al, 2003;Gillies et al, 2004) which, we propose, may arise, to a large extent, from the sexually differentiated cytoarchitecture.…”

Section: Gc Programming Of Midbrain Da Cytoarchitecturementioning

confidence: 60%

“…Numerous investigations suggest that sex steroid hormones, acting either during development or in adulthood, are major determinants of sex differences in the number of total neurons or specific neurotransmitter populations in certain brain nuclei (Forger, 2006). However, it was recently demonstrated that specific expression of the Sry gene in DA neurons of the SNc is responsible for the larger population of TH-IR cells in the male nucleus (Dewing et al, 2006).…”

Section: Midbrain Da Population Sizementioning

confidence: 99%

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The Size and Distribution of Midbrain Dopaminergic Populations are Permanently Altered by Perinatal Glucocorticoid Exposure in a Sex- Region- and Time-Specific Manner

McArthur

McHale

Gillies

2006

Neuropsychopharmacol

111

106

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Central dopaminergic (DA) systems appear to be particularly vulnerable to disruption by exposure to stressors in early life, but the underlying mechanisms are poorly understood. As endogenous glucocorticoids (GCs) are implicated in other aspects of neurobiological programming, this study aimed to characterize the effects of perinatal GC exposure on the cytoarchitecture of DA populations in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA). Dexamethasone was administered non-invasively to rat pups via the mothers' drinking water during embryonic days 16-19 or postnatal days 1-7, with a total oral intake circa 0.075 or 0.15 mg/ kg/day, respectively; controls received normal drinking water. Analysis of tyrosine hydroxylase-immunoreactive cell counts and regional volumes in adult offspring identified notable sex differences in the shape and volume of the SNc and VTA, as well as the topographical organization and size of the DA populations. Perinatal GC treatments increased the DA population size and altered the shape of the SNc and VTA as well as the organization of the DA neurons by expanding and/or shifting them in a caudal direction. This response was sexually dimorphic and included a feminization or demasculinization of the three-dimensional cytoarchitecture in males, and subtle differences that were dependent on the window of exposure. These findings demonstrate that inappropriate perinatal exposure to GCs have enduring effects on the organization of midbrain DA systems that are critically important for normal brain function throughout life.

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Section: Gc Programming Of Midbrain Da Cytoarchitecturementioning

confidence: 60%

Section: Gc Programming Of Midbrain Da Cytoarchitecturementioning

confidence: 60%

Section: Midbrain Da Population Sizementioning

confidence: 99%

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The Size and Distribution of Midbrain Dopaminergic Populations are Permanently Altered by Perinatal Glucocorticoid Exposure in a Sex- Region- and Time-Specific Manner

McArthur

McHale

Gillies

2006

Neuropsychopharmacol

111

106

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“…The ratio of antiapoptotic proteins to proapoptotic proteins plays a key role in determining whether a cell survives or undergoes apoptosis [11][12][13]. In specific brain areas, testicular hormones decrease cell death during perinatal development.…”

Section: Extent Of Global Sexual Dimorphismmentioning

confidence: 99%

Sexual dimorphism in environmental epigenetic programming

Gabory

Attig

Junien

2009

Molecular and Cellular Endocrinology

249

196

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The phenotype of an individual is the result of complex interactions between genotype and current, past and ancestral environment leading to a lifelong remodelling of our epigenomes. The vast majority of common diseases, including atherosclerosis, diabetes, osteoporosis, asthma, neuropsychological and autoimmune diseases, which often take root in early development, display some degree of sex bias, very marked in some cases. This bias could be explained by the role of sex chromosomes, the different regulatory pathways underlying sexual development of most organs and finally, lifelong fluctuating impact of sex hormones. A substantial proportion of dimorphic genes expression might be under the control of sex-specific epigenetic marks. Environmental factors such as social behaviour, nutrition or chemical compounds can influence, in a gender-related manner, these flexible epigenetic marks during particular spatiotemporal windows of life. Thus, finely tuned developmental program aspects, for each sex, may be more sensitive to specific environmental challenges, particularly during developmental programming and gametogenesis, but also throughout the individual's life under the influence of sex steroid hormones and/or sex chromosomes. An unfavourable programming could thus lead to various defects and different susceptibility to diseases between males and females. Recent studies suggest that this epigenetic programming could be sometimes transmitted to subsequent generations in a sex specific manner and lead to transgenerational effects (TGEs).This review summarizes the current understanding in the field of epigenetic programming and highlights the importance of studying both sexes in epidemiological protocols or dietary interventions both in humans and in experimental animal models.

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“…At least one of the mechanisms by which steroid hormones cause changes in hypothalamic morphology is apoptosis, or programmed cell death [52]. When steroid hormones bind to their receptors within target cells that express pro-or anti-apoptotic genes, they activate or inhibit genes that stimulate or inhibit apoptosis, and hence target the neurons for survival or death.…”

Section: Mechanisms For Hormone Effects On Avpv and Sdn-poa Morphologymentioning

confidence: 99%

Developmental programming and endocrine disruptor effects on reproductive neuroendocrine systems

Gore¹

2008

Frontiers in Neuroendocrinology

231

122

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The ability of a species to reproduce successfully requires the careful orchestration of developmental processes during critical time points, particularly the late embryonic and early postnatal periods. This article begins with a brief presentation of the evidence for how gonadal steroid hormones exert these imprinting effects upon the morphology of sexually differentiated hypothalamic brain regions, the mechanisms underlying these effects, and their implications in adulthood. Then, I review the evidence that aberrant exposure to hormonally-active substances such as exogenous endocrine-disrupting chemicals (EDCs), may result in improper hypothalamic programming, thereby decreasing reproductive success in adulthood. The field of endocrine disruption has shed new light on the discipline of basic reproductive neuroendocrinology through studies on how early life exposures to EDCs may alter gene expression via non-genomic, epigenetic mechanisms, including DNA methylation and histone acetylation. Importantly, these effects may be transmitted to future generations if the germline is affected via transgenerational, epigenetic actions. By understanding the mechanisms by which natural hormones and xenobiotics affect reproductive neuroendocrine systems, we will gain a better understanding of normal developmental processes, as well as to develop the potential ability to intervene when development is disrupted.

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Cell death and sexual differentiation of the nervous system

Cited by 143 publications

References 69 publications

The Size and Distribution of Midbrain Dopaminergic Populations are Permanently Altered by Perinatal Glucocorticoid Exposure in a Sex- Region- and Time-Specific Manner

The Size and Distribution of Midbrain Dopaminergic Populations are Permanently Altered by Perinatal Glucocorticoid Exposure in a Sex- Region- and Time-Specific Manner

Sexual dimorphism in environmental epigenetic programming

Developmental programming and endocrine disruptor effects on reproductive neuroendocrine systems

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