Migration of neurons containing gonadotropin releasing hormone (GnRH) in slices from embryonic nasal compartment and forebrain

Tobet, Stuart A.; Hanna, Iris K.; Schwarting, Gerald A.

doi:10.1016/s0165-3806(96)00151-4

Cited by 34 publications

(33 citation statements)

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“…Another intriguing possibility is that aging neurons, like fetal and cancer cells, might be capable of synthesizing LH (Whitfield & Kourides 1985, Krichevsky et al 1995, Yokotani et al 1997. This latter idea is supported by the findings that (1) mRNA for LH has been localized to pyramidal neurons of the cerebral cortex and hippocampus of the aging rat brain (Lee et al 2004), (2) GnRH receptor I (GnRHR I) is localized to extrapituitary cells in the rodent brain including the hippocampus, amygdala, entorhinal cortex, and subiculum, with lower levels in the septum, frontal cortex and hypothalamus (Reubi & Maurer 1984, Badr & Pelletier 1987, Haour et al 1987, Reubi et al 1987, Jennes et al 1988, 1996, Leblanc et al 1988, Badr et al 1989, Ban et al 1990, Thompson & Moss 1992, Crumeyrolle-Arias et al 1994, Pierpaoli & Lesnikov 1997, Lu et al 1999, Granger et al 2004, and (3) the pulsatile release of GnRH I from the hypothalamus is dramatically elevated following menopause (Gill et al 2002, Gore et al 2004. The increased binding of GnRH I to gonadotrope GnRHR I results in dramatic elevations in the synthesis and secretion of gonadotropins following menopause and andropause (Gharib et al 1990, Couzinet & Schaison 1993, Woller et al 2002.…”

Section: Introductionmentioning

confidence: 89%

“…It is not clear whether GnRH I produced by the hypothalamus or by other tissues binds to and signals through these receptors throughout the body. At least for the brain, GnRHR I signaling is likely mediated through GnRH I produced by GnRH I neurons that extend throughout different regions of the brain (Tobet et al 1996, Quanbeck et al 1997, Kim et al 1999, Reed et al 2002. The short serum half-life of GnRH I (approximately 2-3 min; Redding et al 1973, Fauconnier et al 1978 would support autocrine release of GnRH I within the brain, although it has been shown in rats that GnRH I can cross the blood brain barrier (BBB) (Dvorska et al 1992).…”

Section: Functional Consequences Of Gnrh I Induction Of Lh Expressionmentioning

confidence: 99%

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Human neurons express type I GnRH receptor and respond to GnRH I by increasing luteinizing hormone expression

Wilson¹,

Salamat²,

Haasl³

et al. 2006

Journal of Endocrinology

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Gonadotropin-releasing hormone receptor I (GnRHR I) has been localized to the limbic system of the rat brain, although the functional consequences of GnRH signaling through these receptors is unknown. In this paper, we characterize the expression of GnRHR I in the human hippocampus and cortex, and the functionality of GnRHR I in human neuroblastoma cells. Robust GnRHR I immunoreactivity was detected in the cell body as well as along the apical dendrites of pyramidal neurons in the CA2, CA1, and end plate, but was clearly lower in the subiculum of the hippocampus. Immunolabeling was also evident in cortical neurons, including those located in the entorhinal cortex and occipitotemporal gyrus but was not observed within the granular layer of the dentate gyrus. No differences in immunohistochemical staining were observed between control and Alzheimer's disease brain. GnRHR I mRNA and protein (mature, immature, and other variant) expression was detected in human neuroblastoma cells (M17, SH-SY5Y) and rat embryonic primary neurons and varied with differentiation and GnRH treatment. Since GnRHR I was expressed by extrapituitary cells, and hypothalamic GnRH I secretion markedly increases post-menopause/andropause, we treated human M17 neuroblastoma cells cultured in serum-free conditions with GnRH I for 6 h and measured LH expression. M17 neuroblastoma cells express LHb mRNA, while immunoblot analysis indicated the presence of three LH variants (approximately 30, 47, and 60 kDa) that were upregulated by low concentrations of GnRH I, but downregulated at higher GnRH I concentrations. LH expression was also found to increase in differentiating embryonic rat primary cortical neurons. Our results demonstrate that neurons expressing GnRHR I are functional, responding to GnRH I by upregulating LH production. Post-reproductive surges in GnRH I secretion may explain the accumulation of LH in pyramidal neurons of the aged human and rat.

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Section: Introductionmentioning

confidence: 89%

Section: Functional Consequences Of Gnrh I Induction Of Lh Expressionmentioning

confidence: 99%

Human neurons express type I GnRH receptor and respond to GnRH I by increasing luteinizing hormone expression

Wilson¹,

Salamat²,

Haasl³

et al. 2006

Journal of Endocrinology

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“…Organotypic slices have been shown previously to contain the conditions necessary to allow GnRH-1 migration from the developing olfactory system to the basal forebrain while keeping intact their migratory route (Tobet et al, 1996). Thus, retained in these slices are the guidance cues for GnRH-1/olfactory system development that are clearly lacking in immortalized cells.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, some phenotypic/behavioral traits of the cell lines could be a consequence of the immortalization procedure which may alter the expression pattern and the activity of such cells (Martinez de la Escalera and Clapp, 2001). Thus, to evaluate whether HGF acts as a guidance cue during the migration of primary GnRH-1 neurons, we used tissue slices prepared from mouse embryos (Tobet et al, 1996;Bless et al, 2000). Tissue slices that maintain connection between forebrain and nasal compartment were generated from E12.5 whole heads.…”

Section: Discussionmentioning

confidence: 99%

“…Timed pregnant CD-1 mice (Charles River Laboratories) were harvested at E12.5 to generate whole-head organotypic slice cultures following the procedures described previously (Tobet et al, 1996;Bless et al, 2000). Briefly, embryonic heads were embedded in 8% low-gelling-temperature agarose (type VIIa; Sigma-Aldrich), and parasagittal sections were cut at 300 m using a vibratome and placed into Petri dishes containing icecold dissection medium (Leibovitz's L-15; pH 7.4; Invitrogen).…”

Section: Embryonic Slice Culturesmentioning

confidence: 99%

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Hepatocyte Growth Factor Acts as a Motogen and Guidance Signal for Gonadotropin Hormone-Releasing Hormone-1 Neuronal Migration

Giacobini

Messina²,

Wray³

et al. 2007

J. Neurosci.

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Reproduction in mammals is under the control of the hypothalamic neuropeptide gonadotropin hormone-releasing hormone-1 (GnRH-1). GnRH-1-secreting neurons originate during embryonic development in the nasal placode and migrate into the forebrain along olfactory nerves. Gradients of secreted molecules may play a role in this migratory process. In this context, hepatocyte growth factor (HGF) is a potential candidate, because it promotes cell motility in developing brain and has been shown previously to act as a motogen on immortalized GnRH-1 neurons (GN11). In this study, the role of HGF and its receptor Met during development of the GnRH-1 system was examined. GnRH-1 cells express Met during their migration and downregulate its expression once they complete this process. Tissue-type plasminogen activator (tPA), a known HGF activator, is also detected in migratory GnRH-1 neurons. Consistent with in vivo expression, HGF is present in nasal explants, and GnRH-1 neurons express Met. HGF-neutralizing antibody was applied to explants to examine the role of the endogenous growth factor. Migration of GnRH-1 cells and olfactory axon outgrowth were significantly reduced, in line with disruption of a guidance gradient. Exogenous application of HGF to explants increased the distance that GnRH-1 cells migrated, suggesting that HGF also acts as a motogen to GnRH-1 neurons. Functional experiments, performed on organotypic slice cultures, show that creation of an opposing HGF gradient inhibits GnRH-1 neuronal migration. Finally, tPA Ϫ/Ϫ :uPA Ϫ/Ϫ (urokinase-type plasminogen activator Ϫ/Ϫ ) knock-out mice exhibit strong reduction of the GnRH-1 cell population. Together, these data indicate that HGF signaling via Met receptor influences the development of GnRH-1.

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Special relationship of ?-aminobutyric acid to the ventromedial nucleus of the hypothalamus during embryonic development

et al. 1999

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The ventromedial nucleus of the hypothalamus (VMH) is a key nucleus for regulating homeostatic, neuroendocrine, and behavioral functions. We conducted immunocytochemical analyses by using antisera directed against γ‐aminobutyric acid (GABA), its synthetic enzyme glutamic acid decarboxylase (GAD67), GABA‐A receptor subunits (α2, β3, ϵ), estrogen receptor‐α, and Neuropeptide Y (NPY) in the region of the VMH in embryonic mice to identify potential patterning elements for VMH formation. Cells and fibers containing GABA and GAD67 encircled the primordial VMH as early as embryonic day 13 (E13) when the cytoarchitecture of the VMH was not recognizable by Nissl stain. At E16–17 the cytoarchitecture of the VMH became recognizable by Nissl stain as GABAergic fibers invaded the nucleus, continued postnatally, and by adulthood the density of GABAergic fibers was greater inside than outside the VMH. GABA‐A receptor subunit expression (β3 by E13 and α2 by E15) within the primordial VMH suggested potential sensitivity to the surrounding GABA signal. Brain slices were used to test whether fibers from distal or proximal sites influenced VMH development. Coronal Vibratome slices were prepared and maintained in vitro for 0–3 days. Nissl stain analyses showed a uniform distribution of cells in the region of the VMH on the day of plating (E15). After 3 days in vitro, cellular aggregation suggesting VMH formation was seen. Nuclear formation in vitro suggests that key factors resided locally within the coronal plane of the slices. It is suggested that either GABA intrinsic to the region nearby the VMH directly influences the development and organization of the VMH, or along with other markers provides an early indicator of pattern determination that precedes the cellular organization of the VMH. J. Comp. Neurol. 405:88–98, 1999. © 1999 Wiley‐Liss, Inc.

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Migration of neurons containing gonadotropin releasing hormone (GnRH) in slices from embryonic nasal compartment and forebrain

Cited by 34 publications

References 24 publications

Human neurons express type I GnRH receptor and respond to GnRH I by increasing luteinizing hormone expression

Human neurons express type I GnRH receptor and respond to GnRH I by increasing luteinizing hormone expression

Hepatocyte Growth Factor Acts as a Motogen and Guidance Signal for Gonadotropin Hormone-Releasing Hormone-1 Neuronal Migration

Special relationship of ?-aminobutyric acid to the ventromedial nucleus of the hypothalamus during embryonic development

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