Brain-Derived Neurotrophic Factor But Not Neurotrophin-3 Enhances Differentiation of Somatostatin Neurons in Hypothalamic Cultures

Loudes, Catherine; Petit, Florence; Kordon, C.; Faivre-Bauman, A.

doi:10.1159/000054581

Cited by 24 publications

(19 citation statements)

References 29 publications

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“…long-term i.c.v. BDNF administration reproduced the stimulatory effect of BDNF on SRIH content described here (48 h after the single BDNF injection) and those described in previous in vitro studies (Rage et al 1999, Loudes et al 2000. Using this paradigm, contrary to the findings after the acute injection, no temporal correlation between changes in PeVN mRNA levels and peptide hypothalamic contents were observed.…”

Section: Figuresupporting

confidence: 85%

Involvement of brain-derived neurotrophic factor in the regulation of hypothalamic somatostatin in vivo

Givalois¹,

Naert²,

Tapia‐Arancibia³

et al. 2006

Journal of Endocrinology

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Brain-derived neurotrophic factor (BDNF) has been extensively studied in the central nervous system as a survival and differentiation factor and in plasticity processes. In vitro, BDNF has been shown to stimulate cellular differentiation and neurohormones synthesis and release. We demonstrated that BDNF is a potent and specific stimulatory agent of somatostatin (SRIH) synthesis in primary cultures of hypothalamic neurons. However, less information is available about its function on SRIH neurons in vivo. In the present study, we examined the effect of in vivo intracerebroventricular BDNF administration in adult non-anesthetized male rats. Two distinct experimental approaches were used: acute intracerebroventricular injection and long-term (14 days) continuous infusion (Alzet micro-pumps). We demonstrate that single intracerebroventricular BDNF injections (5 µg/rat) induce an early (60 and 180 min) decrease in the SRIH mRNA signal in the hypothalamic periventricular nucleus (PeVN) accompanied by a decrease of the hypothalamic SRIH content. 48 h after the acute injection, SRIH mRNA levels and peptide content strongly and significantly increased. After continuous intracerebroventricular BDNF administration (12 µg/day for 14 days), a significant increase in the SRIH hypothalamic content was observed. Nevertheless, the increase in peptide content was not correlated with a similar increase in the PeVN messenger level. These findings show the involvement of BDNF in the in vivo regulation of somatostatinergic neurons in adult rats, which clearly differs according to the BDNF administration mode.

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Section: Figuresupporting

confidence: 85%

Involvement of brain-derived neurotrophic factor in the regulation of hypothalamic somatostatin in vivo

Givalois¹,

Naert²,

Tapia‐Arancibia³

et al. 2006

Journal of Endocrinology

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“…Under the same conditions, SRIH neurons were found to exhibit normal morphological and functional maturation in vitro [11], and NPY neurons can be detected immunocytochemically at 14 DIV [Faivre-Bauman and Loudes, unpubl. results], indicating that the culture conditions are compatible with normal neuronal development.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies in Arc or Pev cultures have suggested that dopaminergic [7]and somatostatinergic neurons [11]represent less than 1 and 4–7%, respectively, of the total neuronal population. Corresponding PCR figures reported here are much higher (over 10 and 50%, respectively).…”

Section: Discussionmentioning

confidence: 99%

“…Cultures were maintained in serum-free medium in the presence or absence of human recombinant NT3 or BDNF (50 ng/ml ; Promega, Madison, Wisc., USA) added at seeding time and at medium renewal on the 4th DIV and left until 6 DIV. This neurotrophin concentration was previously found optimal in the same in vitro model [7, 11]. Cytosine arabinoside (1 µ M , Sigma, St. Quentin, Fallavier, France) was added from 4 DIV onwards to block glial cell proliferation.…”

Section: Methodsmentioning

confidence: 98%

“…In parallel, trkB and trkC, the high affinity receptors of BDNF and NT3, are also expressed in cultured hypothalamic neurons [9, 10]. Exogenous BDNF and NT3 selectively enhance morphological and functional differentiation of cultured dopaminergic [7]and somatostatinergic [11]neurons from two distinct hypophysiotropic regions, the arcuate (Arc) and the periventricular (Pev) nuclei.…”

Section: Introductionmentioning

confidence: 99%

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The Neurotrophins NT3 and BDNF Induce Selective Specification of Neuropeptide Coexpression and Neuronal Connectivity in Arcuate and Periventricular Hypothalamic Neurons in vitro

Petit¹,

Huicq²,

Gardette³

et al. 2002

Neuroendocrinology

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Little is known on the influence of epigenetic factors in the developing hypothalamus, a region particularly involved in neuroendocrine regulation and rich in neuropeptides. The present study evaluated the effects of neurotrophins and neuronal activity on neuronal differentiation in hypothalamic cultures sampled from either arcuate or anterior periventricular regions of 17-day-old Sprague-Dawley fetuses. Expression of neuropeptides, tyrosine hydroxylase, neurotrophins and neurotrophin receptors was tested on young (6 days in vitro, DIV) and more mature (14 DIV) cultured neurons by multiple reverse transcription polymerase chain reaction on single cells. In parallel, spontaneous postsynaptic currents were recorded as an index of neuronal connectivity. Neurotrophin-3 (NT3) was expressed in a much larger population of neurons than brain-derived neurotrophic factor (BDNF) at both culture times. At 6 DIV, synaptic currents were scarce and expression of the neurotrophin receptors trkB and trkC was found in a small proportion of neurons only. These parameters increased markedly between 6 and 14 DIV, and also upon addition of neurotrophins. The most striking consequence of arcuate neuron maturation in vitro between 6 and 14 DIV was a marked phenotypic specification affecting somatostatin, neuropeptide Y and pro-opiomelanocortin, the three major neuropeptides expressed in the cultures. NT3, but not BDNF, was able to reproduce maturation-related phenotypic specification in 6 DIV arcuate cultures. Maturation-dependent phenotypic specification was less marked in periventricular cultures; in that case BDNF, not NT3 had a slight effect on phenotype specification. It is concluded that NT3 plays a selective role in phenotypic specification of neuropeptides in the arcuate region, whereas other maturation parameters (neurotrophin receptor expression and/or synaptogenesis) can be potentiated by either neurotrophin in both structures.

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Regulation of brain‐derived neurotrophic factor transcripts by neuronal activation in rat hypothalamic neurons

Marmigère¹,

Rage²,

Tapia‐Arancibia³

2001

J of Neuroscience Research

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Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family and regulates the survival, differentiation, and maintenance of function in different neuronal populations. BDNF is strongly expressed in hypothalamic neurons, where it exerts long- or short-lasting actions. Because glutamate has been associated with regulations of hypothalamic hormones, we examined the regulation of the four promoters of the BDNF gene by glutamate in fetal hypothalamic neurons. The expression levels of BDNF transcripts were investigated using semiquantitative RT-PCR. BDNF protein was determined by enzyme immunoassay, and BDNF and Trk B (BDNF receptor) gene variations were determined by RNAse protection assay. By RT-PCR, we showed that, under basal conditions, BDNF transcripts from exons I, II, and III but not from IV were expressed in the hypothalamic neurons. Glutamate increased expression of both the protein and the four transcripts via N-methyl-D-aspartate receptors, with maximal stimulations after 3 hr of application for exon I and II mRNAs and after 1 hr for exon III and IV mRNAs. Actinomycin D blocked the increase of all transcripts, whereas cycloheximide treatment inhibited stimulation only of exon I and II mRNAs. Trk B mRNA was rapidly and transiently reduced after glutamate application. Our results demonstrate that glutamate 1) regulates BDNF mRNA expression at an early developmental stage in hypothalamic neurons and 2) exerts a differential regulation of BDNF transcripts.

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Brain-Derived Neurotrophic Factor But Not Neurotrophin-3 Enhances Differentiation of Somatostatin Neurons in Hypothalamic Cultures

Cited by 24 publications

References 29 publications

Involvement of brain-derived neurotrophic factor in the regulation of hypothalamic somatostatin in vivo

Involvement of brain-derived neurotrophic factor in the regulation of hypothalamic somatostatin in vivo

The Neurotrophins NT3 and BDNF Induce Selective Specification of Neuropeptide Coexpression and Neuronal Connectivity in Arcuate and Periventricular Hypothalamic Neurons in vitro

Regulation of brain‐derived neurotrophic factor transcripts by neuronal activation in rat hypothalamic neurons

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