Time of neuron origin and gradients of neurogenesis in midbrain dopaminergic neurons in the mouse

Bayer, Shirley A.; Wills, Katherine V.; Triarhou, Lazaros C.; Ghetti, Bernardino

doi:10.1007/bf00240955

Cited by 161 publications

(156 citation statements)

References 29 publications

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“…No significant effects of gender, treatment or level in the SNc or VTA were detected. However, in agreement with others (German and Manaye, 1993;Bayer et al, 1995;Lieb et al, 1996) the DA cells in the SNc were significantly larger than those of the VTA (po0.01).…”

Section: Th-ir Cell Size and Packing Densitysupporting

confidence: 92%

“…In the rat the final mitosis of DA progenitor cells occurs between E12 and E16 (Bayer et al, 1995;Lieb et al, 1996), which just overlaps with our pretreatment regimen beginning at E16. However, if findings based on proliferation rate of the granule cells in the hippocampal dentate gyrus are more generally applicable (Gould and Cameron, 1996), it would be predicted that adrenal steroids might decrease neurogenesis, which would not be compatible with our reported increase in midbrain DA cell numbers.…”

Section: Midbrain Da Population Sizesupporting

confidence: 67%

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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

110

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: Th-ir Cell Size and Packing Densitysupporting

confidence: 92%

Section: Midbrain Da Population Sizesupporting

confidence: 67%

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

110

106

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“…It should be noted that even though it is expected that fetal development progresses at different rates in rodents and humans, there are also significant differences between rats and mice. In fact, many key developmental events occur approximately 2 days later in rats compared to mice during prenatal and perinatal periods (Bayer et al, 1995;Clancy et al, 2007). The gestational length is 19-21 days in mice and 21-23 days in rats.…”

Section: Methodological Considerationsmentioning

confidence: 99%

Sex effects on neurodevelopmental outcomes of innate immune activation during prenatal and neonatal life

Rana

Aavani

Pittman

2012

Hormones and Behavior

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Humans are exposed to potentially harmful agents (bacteria, viruses, toxins) throughout our lifespan; the consequences of such exposure can alter central nervous system development. Exposure to immunogens during pregnancy increases the risk of developing neurological disorders such as schizophrenia and autism. Further, sex hormones, such as estrogen, have strong modulatory effects on immune function and have also been implicated in the development of neuropathologies (e.g., schizophrenia and depression). Similarly, animal studies have demonstrated that immunogen exposure in utero or during the neonatal period, at a time when the brain is undergoing maturation, can induce changes in learning and memory, as well as dopaminemediated behaviors in a sex-specific manner. Literature that covers the effects of immunogens on innate immune activation and ultimately the development of the adult brain and behavior is riddled with contradictory findings, and the addition of sex as a factor only adds to the complexity. This review provides evidence that innate immune activation during critical periods of development may have effects on the adult brain in a sex-specific manner. Issues regarding sex bias in research as well as variability in animal models of immune function are discussed.

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“…Regarding developmental stages, to consider the hVMl cells as VM DAn precursors is not in conflict with the gestational age of the fetus from which they were derived (10 weeks post conception (PC) [34]). This age is roughly equivalent to E14 in mice, a time when TH neurogenesis is considered over [69]. However, seminal studies indicate that, in humans, neurogenesis is protracted in time, peaking during PC weeks 6.5 to 8 and finishing by PC week 10-11, a stage where newborn TH + neurons are still present in the ventricular zone and have not yet migrated to the mantle zone [70].…”

Section: Regionalization and Activation Of Developmental Gene Cascadementioning

confidence: 99%

Human midbrain precursors activate the expected developmental genetic program and differentiate long-term to functional A9 dopamine neurons in vitro. Enhancement by Bcl-XL

Seiz

Ramos-Gómez

Courtois

et al. 2012

Experimental Cell Research

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Understanding the molecular programs of the generation of human dopaminergic neurons (DAn) from their ventral mesencephalic (VM) precursors is of key importance for basic studies, progress in cell therapy, drug screening and pharmacology in the context of Parkinson's disease. The nature of human DAn precursors in vitro is poorly understood, their properties unstable, and their availability highly limited. Here we present positive evidence that human VM precursors retaining their genuine properties and long-term capacity to generate A9 type Substantia nigra human DAn (hVMl model cell line) can be propagated in culture. During a one month differentiation, these cells activate all key genes needed to progress from pro-neural and prodopaminergic precursors to mature and functional DAn. For the first time, we demonstrate that gene cascades are correctly activated during differentiation, resulting in the generation of mature DAn. These DAn have morphological and functional properties undistinguishable from those generated by VM primary neuronal cultures. In addition, we have found that the forced expression of Bcl-X L induces an increase in the expression of key developmental genes (MSX1, Abbreviations: A9-DAn, (dopaminergic neuron from the A9 group); 6-OHDA, (6-hidroxydopamine); DA, (dopamine); DAn, (dopaminergic neuron); FB, (forebrain); FP, (floor plate); hESC, (human Embryonic stem cells); hNSC, (human neural stem cells); hVM, (human ventral mesencephalon); SNpc, (substantia nigra pars compacta); TH, (tyrosine hydroxylase); VM, (ventral mesencephalon); VM DAn, (dopaminergic neuron from ventral mesencephalon); VM hNSC, (human neural stem cells from ventral mesencephalon) NGN2), maintenance of PITX3 expression temporal profile, and also enhances genes involved in DAn long-term function, maintenance and survival (ENl, LMXIB, NURRl and PITX3). As a result, Bcl-X L anticipates and enhances DAn generation.

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Time of neuron origin and gradients of neurogenesis in midbrain dopaminergic neurons in the mouse

Cited by 161 publications

References 29 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

Sex effects on neurodevelopmental outcomes of innate immune activation during prenatal and neonatal life

Human midbrain precursors activate the expected developmental genetic program and differentiate long-term to functional A9 dopamine neurons in vitro. Enhancement by Bcl-XL

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