Dopamine depletion impairs precursor cell proliferation in Parkinson disease

Höglinger, Günter U.; Rizk, Pamela; Muriel, Marie‐Paule; Duyckaerts, Charles; Oertel, Wolfgang H.; Caillé, Isabelle; Hirsch, Étienne C.

doi:10.1038/nn1265

Cited by 844 publications

(960 citation statements)

References 44 publications

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“…D5R mRNA was significantly higher in this region compared to the embryonic proliferative domains. Once again, expression of dopamine receptor mRNAs is consistent with the reported effects of dopamine receptor agonists and antagonists on cell proliferation in the subventricular zone [15,20,53,54]. Each brain region showed unique characteristics with respect to developmental regulation of the five mRNAs.…”

Section: Discussionsupporting

confidence: 84%

Dopamine receptor mRNA and protein expression in the mouse corpus striatum and cerebral cortex during pre- and postnatal development

2007

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The outcome of dopaminergic signaling and effectiveness of dopaminergic drugs depend on the relative preponderance of each of the five dopamine receptors in a given brain region. The separate contribution of each receptor to overall dopaminergic tone is difficult to establish at a functional level due to lack of receptor subtype specific pharmacological agents. A surrogate for receptor function is receptor protein or mRNA expression. We examined dopamine receptor mRNA expression by quantitative reverse transcription real-time PCR in the striatum, globus pallidus, frontal cortex and cingulate cortex of embryonic and postnatal mice. Samples of each region were collected by laser capture microdissection. D1-and D2-receptor mRNAs were the most abundant in all the regions of the mature brain. The D1-receptor was predominant over the D2-receptor in the frontal and cingulate cortices whereas the situation was reversed in the striatum and globus pallidus. In the proliferative domains of the embryonic forebrain, D3-, D4-and D5-receptors were predominant. In the corpus striatum and cerebral cortex, the D3-and D4-receptors were the only receptors that showed marked developmental regulation. By analyzing D1 receptor protein expression, we show that developmental changes in mRNA expression reliably translate into changes in protein levels, at least for the D1-receptor.

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Section: Discussionsupporting

confidence: 84%

Dopamine receptor mRNA and protein expression in the mouse corpus striatum and cerebral cortex during pre- and postnatal development

2007

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“…Many acute brain insults such as ischemia, hypoxia, seizures, and trauma enhance neurogenesis (fore review see Min and Song, 2005). Similarly, increased neurogenesis is also found in various neurodegenerative diseases (Curtis, et al, 2003, Hoglinger, et al, 2004, Jin, et al, 2004a, indicating that chronic insults can trigger neurogenesis too. Together with all those findings, our results suggest that neurogenesis may work as a universal protective mechanism endogenously for the brain to against different neuronal insults.…”

Section: Discussionmentioning

confidence: 88%

“…Moreover, certain acute brain injuries such as ischemia, hypoxia, seizures, and trauma increase neurogenesis (Kokaia and Lindvall, 2003, Rice, et al, 2003, Itoh, et al, 2005, Overstreet-Wadiche, et al, 2006, Qiu, et al, 2007, suggesting that neurogenesis may work as a protective mechanism for the brain. Interestingly, enhanced neurogenesis was recently found in brains of neurodegenerative diseases including Huntington's disease (Curtis, et al, 2003), Parkinson's disease (Hoglinger, et al, 2004), and AD (Jin, et al, 2004a). However, neither the course of neurogenesis during the neurodegenerative processes nor the functional significance of neurogenesis in neurodegeneration is well understood.…”

Section: Introductionmentioning

confidence: 99%

Adult neurogenesis is functionally associated with AD-like neurodegeneration

Chen

Nakajima

Choi

et al. 2008

Neurobiology of Disease

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Alzheimer's disease (AD) is predominantly characterized by progressive neuronal loss in the brain. It has been recently found that adult neurogenesis in the hippocampal dentate gyrus of AD patients is significantly enhanced, while its functional significance is still unknown. By using an AD-like neurodegeneration mouse model, we show here that neurogenesis in the dentate gyrus was neurodegenerative stage-dependent. At early stages of neurodegeneration, neurogenesis was significantly enhanced and newly generated neurons migrated into the local neuronal network. Up to late stages of neurodegeneration, however, the survival of newly generated neurons was impaired so that the enhanced neurogenesis could not be detected any more. Most interestingly, these dynamic changes in neurogenesis were correlated with the severity of neuronal loss in the dentate gyrus, indicating that neurogenesis may work as a self-repairing mechanism to compensate for neurodegeneration. Therefore, to enhance endogenous neurogenesis at early stages of neurodegeneration may be a valuable strategy to delay neurodegenerative progress.

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“…Wood et al, 2001;Berg et al, 2006;Dekeyne et al, 2008;Chanrion et al, 2008;Millan MJ unpublished observations). The notion that inverse agonism is required for enhancing proliferation in the VH is supported by evidence that certain cerebral populations of 5-HT 2C receptors are constitutively active (Berg et al, 2005), including sites tonically inhibitory, through GABAergic interneurones, to ascending dopaminergic or noradrenergic systems that are known to increase cell proliferation (Invernizzi et al, 2007;Hoglinger et al, 2004;Kulkarni et al, 2002;Millan et al, 2008;Aloyo et al, 2009). However, the interpretation of these data is also complicated by the fact that constitutive activity at 5-HT 2C sites is regulated by mRNA editing that differs between brain regions; extensively edited 5-HT 2C receptor isoforms being constitutively silent (Burns et al, 1997;Sanders-Bush et al, 2003).…”

Section: Figurementioning

confidence: 99%

Mechanisms Contributing to the Phase-Dependent Regulation of Neurogenesis by the Novel Antidepressant, Agomelatine, in the Adult Rat Hippocampus

Soumier¹,

Banasr²,

Lortet³

et al. 2009

Neuropsychopharmacol

145

138

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Agomelatine is a novel antidepressant acting as a melatonergic receptor agonist and serotonergic (5-HT 2C ) receptor antagonist. In adult rats, chronic agomelatine treatment enhanced cell proliferation and neurogenesis in the ventral hippocampus (VH), a region pertinent to mood disorders. This study compared the effects of agomelatine on cell proliferation, maturation, and survival and investigated the cellular mechanisms underlying these effects. Agomelatine increased the ratio of mature vs immature neurons and enhanced neurite outgrowth of granular cells, suggesting an acceleration of maturation. The influence of agomelatine on maturation and survival was accompanied by a selective increase in the levels of BDNF (brain-derived neurotrophic factor) vs those of VEGF (vascular endothelial factor) and IGF-1 (insulin-like growth factor 1), which were not affected. Agomelatine also activated several cellular signals (extracellular signal-regulated kinase1/2, protein kinase B, and glycogen synthase kinase 3b) known to be modulated by antidepressants and implicated in the control of proliferation/survival. Furthermore, as agomelatine possesses both melatonergic agonist and serotonergic (5-HT 2C ) antagonist properties, we determined whether melatonin and 5-HT 2C receptor antagonists similarly influence cell proliferation and survival. Only the 5-HT 2C receptor antagonists, SB243,213 or S32006, but not melatonin, mimicked the effects of agomelatine on cell proliferation in VH. The promoting effect of agomelatine on survival was not reproduced by the 5-HT 2C receptor antagonists or melatonin alone. However, it was blocked by a melatonin antagonist, S22153. These results show that agomelatine treatment facilitates all stages of neurogenesis and suggest that a joint effect of melatonin agonism and 5HT 2C antagonism may be involved in promotion by agomelatine of survival in the hippocampus.

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Dopamine depletion impairs precursor cell proliferation in Parkinson disease

Cited by 844 publications

References 44 publications

Dopamine receptor mRNA and protein expression in the mouse corpus striatum and cerebral cortex during pre- and postnatal development

Dopamine receptor mRNA and protein expression in the mouse corpus striatum and cerebral cortex during pre- and postnatal development

Adult neurogenesis is functionally associated with AD-like neurodegeneration

Mechanisms Contributing to the Phase-Dependent Regulation of Neurogenesis by the Novel Antidepressant, Agomelatine, in the Adult Rat Hippocampus

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