Singular subsets of locus coeruleus neurons may recover tyrosine hydroxylase phenotype transiently expressed during development

Bezin, Laurent; Marcel, Dominique; Desgeorges, Sébastien; Pujol, Jean‐François; Weissmann, Dinah

doi:10.1016/s0169-328x(00)00007-3

Cited by 25 publications

(21 citation statements)

References 19 publications

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“…In TgNTRK3 mice the LC phenotype could thus emanate from the alteration of both BDNF and NT-3 systems. Interestingly, neurotrophins can recover a noradrenergic phenotype in ‘resting noradrenergic’ neurons in the adult LC (Bezin et al, 2000), a mechanism that could be involved in the pathological alteration of LC in psychiatric conditions such as panic disorder or substance abuse. Chronic opiate treatment and withdrawal differentially regulate neurotrophin and their receptor mRNAs in catecholaminergic nuclei (Seroogy et al, 1994; Hung and Lee, 1996; Numan et al, 1998; Numan and Seroogy, 1999).…”

Section: Discussionmentioning

confidence: 99%

Increased opioid dependence in a mouse model of panic disorder

Gallego

Murtra

Zamalloa

et al. 2009

Front. Behav. Neurosci.

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Panic disorder is a highly prevalent neuropsychiatric disorder that shows co-occurrence with substance abuse. Here, we demonstrate that TrkC, the high-affinity receptor for neurotrophin-3, is a key molecule involved in panic disorder and opiate dependence, using a transgenic mouse model (TgNTRK3). Constitutive TrkC overexpression in TgNTRK3 mice dramatically alters spontaneous firing rates of locus coeruleus (LC) neurons and the response of the noradrenergic system to chronic opiate exposure, possibly related to the altered regulation of neurotrophic peptides observed. Notably, TgNTRK3 LC neurons showed an increased firing rate in saline-treated conditions and profound abnormalities in their response to met5-enkephalin. Behaviorally, chronic morphine administration induced a significantly increased withdrawal syndrome in TgNTRK3 mice. In conclusion, we show here that the NT-3/TrkC system is an important regulator of neuronal firing in LC and could contribute to the adaptations of the noradrenergic system in response to chronic opiate exposure. Moreover, our results indicate that TrkC is involved in the molecular and cellular changes in noradrenergic neurons underlying both panic attacks and opiate dependence and support a functional endogenous opioid deficit in panic disorder patients.

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Section: Discussionmentioning

confidence: 99%

Increased opioid dependence in a mouse model of panic disorder

Gallego

Murtra

Zamalloa

et al. 2009

Front. Behav. Neurosci.

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“…The plasticity of these neurons is apparently not restricted to the developmental period because dormant NA neurons in the LC of the adult brain can also re-express NA traits when stimulated by appropriate treatments in vivo (Bezin et al, 2000). The possible involvement of CRF and BDNF in this process remains a subject for further study.…”

Section: Discussionmentioning

confidence: 99%

“…Because of the ubiquitous distribution of NA, the LC-NA system plays a prominent role in a variety of brain functions and behaviors that include vigilance, attention, arousal, memory acquisition, locomotor control, and response to stress (Berridge and Waterhouse, 2003). LC NA neurons are also interesting for other reasons: 1) via their neurotransmitter, they influence the development and survival of other populations of neuronal cells either during development of the brain or later in life (Meier et al, 1991;Marien et al, 2004); 2) some of them can recover in the adult brain a phenotype that they transiently expressed during development (Bezin et al, 2000); and 3) they are vulnerable to neurodegenerative conditions such as Alzheimer's and Parkinson's diseases (Zarow et al, 2003) and represent a potential target for pharmacological treatments of these disorders (Marien et al, 2004). Because of these multiple attributes, it is vital to understand the factors and signals that control the phenotype and/or survival of these neurons.…”

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confidence: 99%

The Phenotypic Differentiation of Locus Ceruleus Noradrenergic Neurons Mediated by Brain-Derived Neurotrophic Factor Is Enhanced by Corticotropin Releasing Factor through the Activation of a cAMP-Dependent Signaling Pathway

Traver¹,

Marien²,

Martin³

et al. 2006

Molecular Pharmacology

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We have developed a model system of locus ceruleus (LC) neurons in culture, in which brain-derived neurotrophic factor (BDNF) induces the emergence of noradrenergic neurons attested by the presence of tyrosine hydroxylase (TH) and dopamine-␤-hydroxylase and the absence of phenylethanolamine N-methyl-transferase. Although inactive in itself, the neuropeptide corticotropin releasing factor (CRF) strongly amplified the effect of BDNF, increasing the number of cells expressing TH and the active accumulation of noradrenaline by a factor of 2 to 3 via a mechanism that was nonmitogenic. CRF also acted cooperatively with neurotrophin-4, which like BDNF is a selective ligand of the TrkB tyrosine kinase receptor. The effect of CRF but not that of BDNF was prevented by astressin, a nonselective CRF-1/CRF-2 receptor antagonist. However, only CRF-1 receptor transcripts were detectable in LC cultures, suggesting that this receptor subtype mediated the effect of CRF. Consistent with the positive coupling of CRF-1 receptors to adenylate cyclase, the trophic action of CRF was mimicked by cAMP elevating agents. Epac, a guanine nucleotide exchange factor directly activated by cAMP, contributed to the effect of CRF through the stimulation of extracellular signalregulated kinases (ERKs) 1/2. However, downstream of ERK1/2 activation by CRF, the phenotypic induction of noradrenergic neurons relied upon the stimulation of the phosphatidylinositol-3-kinase/Akt transduction pathway by BDNF. Together, our results suggest that CRF participates to the phenotypic differentiation of LC noradrenergic neurons during development. Whether similar mechanisms account for the high degree of plasticity of these neurons in the adult brain remains to be established.The majority of noradrenergic (NA) neurons in the brain are localized within a single brainstem nucleus, the locus ceruleus (LC). However, because of a widespread projection system, these neurons innervate almost the entire central nervous system (Berridge and Waterhouse, 2003). Because of the ubiquitous distribution of NA, the LC-NA system plays a prominent role in a variety of brain functions and behaviors that include vigilance, attention, arousal, memory acquisition, locomotor control, and response to stress (Berridge and Waterhouse, 2003). LC NA neurons are also interesting for other reasons: 1) via their neurotransmitter, they influence the development and survival of other populations of neuronal cells either during development of the brain or later in life (Meier et al., 1991;Marien et al., 2004); 2) some of them can recover in the adult brain a phenotype that they transiently expressed during development (Bezin et al., 2000); and 3) they are vulnerable to neurodegenerative conditions such as Alzheimer's and Parkinson's diseases (Zarow et al., 2003) and represent a potential target for pharmacological This work was supported by Centre de Recherche Pierre Fabre and Institut National de la Santé et de la Recherche Médicale.Article, publication date, and citation information can...

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“…These findings, together with our previous study, might suggest that the lack of effect of undernutrition on the number of neurons at P12 is associated with the maximal organizational period in the LC, which occurs in the second week and may compensate for the effects of undernutrition. In addition, the second week of postnatal life is a crucial period for the development of several morphological and neurochemical characteristics of the LC, including the tyrosine hydroxylase (TH) content of the cell (Zyzek et al 1990;Benzin et al 1994;Rousset et al 1994;Benzin et al 1997;Benzin et al 2000), reorganization of cellular bodies (Sisk and Foster 2004) and number of TH positive cells in the LC, which reaches a maximum by day P14 (Benzin et al 1994). An important question arising from these results concerns whether the number of LC neurons can be recovered to control values if nutritional rehabilitation starts at earlier stages of development.…”

Section: Discussionmentioning

confidence: 99%

Early undernutrition decreases the number of neurons in the locus coeruleus of rats

Pinos

Collado

Salas

et al. 2006

Nutritional Neuroscience

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The effects of perinatal undernutrition on the number of neurons and apoptotic cells of the locus coeruleus (LC) of female and male rats at postpartum days 7, 12, 20, 30 and 60 were studied. Undernutrition reduces the number of neurons in both sexes without affecting cell death, as indicated by the ratio of apoptotic cells to neurons. The data suggest that in the undernourished groups lower rates of neurogenesis and proliferation (neurogenetic/proliferation rates) might avoid these animals achieving the number of LC neurons as in the control subjects. Although food restriction in both sexes apparently provokes the loss of cells, the effect does not appear to be equal in females and males, as shown by post weaning food rehabilitation. The results suggest that severe food deprivation may interfere with the ontogenetic processes underlying neuronal differentiation of the LC. Morphological damage in the LC due to undernutrition might alter the physiology of sexual and/or feeding behaviours in which this structure is implicated.

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Singular subsets of locus coeruleus neurons may recover tyrosine hydroxylase phenotype transiently expressed during development

Cited by 25 publications

References 19 publications

Increased opioid dependence in a mouse model of panic disorder

Increased opioid dependence in a mouse model of panic disorder

The Phenotypic Differentiation of Locus Ceruleus Noradrenergic Neurons Mediated by Brain-Derived Neurotrophic Factor Is Enhanced by Corticotropin Releasing Factor through the Activation of a cAMP-Dependent Signaling Pathway

Early undernutrition decreases the number of neurons in the locus coeruleus of rats

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