Ciliary neurotrophic factor prevents degeneration of adult rat substantia nigra dopaminergic neurons in vivo.

Hagg, Theo; Varon, Silvio

doi:10.1073/pnas.90.13.6315

Cited by 211 publications

(110 citation statements)

References 49 publications

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“…Male C57BL/6 mice (10 weeks of age; 18 -22 g; The Jackson Laboratory) were anesthetized and unilaterally injected with 1.5 g (per injection site) 6-hydroxydopamine (6-OHDA; Sigma-Aldrich) in 0.5 l of saline containing 0.2% ascorbic acid (n ϭ 4) or with saline containing 0.2% ascorbic acid (n ϭ 4) into the right medial forebrain bundle and the substantia nigra at stereotaxic coordinates from Bregma: 1.1 mm caudal, 1.3 mm lateral, 5.3 mm from the dura mater and 3.3 mm caudal, 1.3 mm lateral, 4.8 mm from the dura mater, respectively. Dopaminergic neurons of the substantia nigra pars compacta project ipsilaterally to the neostriatum (Hagg and Varon, 1993), and the terminals are lost after the 6-OHDA lesion. One week after injury, the brains were freshly dissected to obtain the strip SVZ/striatal tissue for RNA isolation and CNTF mRNA measurements.…”

Section: Methodsmentioning

confidence: 99%

“…Identifying the molecular mechanisms regulating CNTF expression in vivo and their pharmacological modulators is important, because CNTF is neuroprotective (Hagg and Varon, 1993;Thoenen and Sendtner, 2002) and enhances adult CNS neurogenesis (Emsley and Hagg, 2003). Dopaminergic projections (Baker et al, 2004;Hoglinger et al, 2004) and a D 2 agonist (Hoglinger et al, 2004) also promote neurogenesis, suggesting that dopamine might stimulate CNTF expression in the neurogenic ϩ SVZ nuclei when CNTF-specific neutralizing antibodies were simultaneously infused into the lateral ventricle of C57BL/6 mice.…”

Section: Dopaminergic Pathways Regulate Cntf Expression In Astrocytesmentioning

confidence: 99%

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Ciliary Neurotrophic Factor Mediates Dopamine D₂Receptor-Induced CNS Neurogenesis in Adult Mice

Yang¹,

Arnold²,

Habas³

et al. 2008

J. Neurosci.

141

149

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Neurogenesis continues in the adult forebrain subventricular zone (SVZ) and the dentate gyrus of the hippocampal formation. Degeneration of dopaminergic projections in Parkinson's disease and animals reduces, whereas ciliary neurotrophic factor (CNTF) promotes, neurogenesis. We tested whether the dopaminergic system promotes neurogenesis through CNTF. Astrocytes of the SVZ and dentate gyrus expressed CNTF and were close to dopaminergic terminals. Dopaminergic denervation in adult mice reduced CNTF mRNA by ϳ60%, whereas systemic treatment with the D 2 agonist quinpirole increased CNTF mRNA in the SVZ and hippocampal formation, and in cultured astrocytes by 1.5-5 fold. The effect of quinpirole in vitro was blocked by the D 2 antagonist eticlopride and did not cause astroglial proliferation or hypertrophy. Systemic quinpirole injections increased proliferation in wild-type mice by ϳ25-75% but not in CNTF

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Section: Methodsmentioning

confidence: 99%

Section: Dopaminergic Pathways Regulate Cntf Expression In Astrocytesmentioning

confidence: 99%

Ciliary Neurotrophic Factor Mediates Dopamine D₂Receptor-Induced CNS Neurogenesis in Adult Mice

Yang¹,

Arnold²,

Habas³

et al. 2008

J. Neurosci.

141

149

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“…The etiology of this selective cell loss remains unknown. Local availability of trophic factors is able to protect cells from degeneration in animal models of PD (3)(4)(5)(6), suggesting that lack of trophic support could contribute to the observed neurodegeneration in normal aging and in PD. Furthermore, morphological characteristics of apoptotic cell death have been reported in brain sections from PD patients (7,8), but the involvement of apoptosis in PD is still controversial.…”

mentioning

confidence: 99%

Tetrahydrobiopterin Enhances Apoptotic PC12 Cell Death following Withdrawal of Trophic Support

Anastasiadis

Jiang

Bezin

et al. 2001

Journal of Biological Chemistry

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(6R)-Tetrahydro-L-biopterin (BH 4 ) is the rate-limiting cofactor in the production of catecholamine and indoleamine neurotransmitters and is also essential for the synthesis of nitric oxide by nitric-oxide synthase. We have previously reported that BH 4 administration induces PC12 cell proliferation and that nerve growth factor-or epidermal growth factor-induced PC12 cell proliferation requires the elevation of intracellular BH 4 levels. We show here that BH 4 accelerates apoptosis in undifferentiated PC12 cells deprived of serum and in differentiated neuron-like PC12 cells after nerve growth factor withdrawal. Increased production of catecholamines or nitric oxide cannot account for the enhancement of apoptosis by BH 4 . Furthermore, increased calcium influx by exogenous BH 4 administration is not involved in the BH 4 proapoptotic effect. Our data also argue against the possibility that increased oxidative stress, due to BH 4 autoxidation, is responsible for the observed BH 4 effects. Instead, they are consistent with the hypothesis that BH 4 induces apoptosis by increasing cell cycle progression. Elevation of intracellular BH 4 during serum withdrawal increased c-Myc (and especially Myc S) expression earlier than serum withdrawal alone. Furthermore, N-acetylcysteine and the cyclin-dependent kinase inhibitor olomoucine ameliorated the BH 4 proapoptotic effect. These data suggest that BH 4 affects c-Myc expression and cell cycle-dependent events, possibly accounting for its effects on promoting cell cycle progression or apoptosis.Apoptotic cell death is important for normal nervous system development, where neurons that make proper connections and receive sufficient trophic support survive, whereas neurons that are deprived of trophic support die via apoptosis (for a review, see Ref. 1). The requirement for neurotrophic support is thought to continue in mature neurons (for a review, see Ref.2). During normal aging and in Parkinson's disease (PD), 1 nigrostriatal dopamine neurons preferentially degenerate. The etiology of this selective cell loss remains unknown. Local availability of trophic factors is able to protect cells from degeneration in animal models of PD (3-6), suggesting that lack of trophic support could contribute to the observed neurodegeneration in normal aging and in PD. Furthermore, morphological characteristics of apoptotic cell death have been reported in brain sections from PD patients (7, 8), but the involvement of apoptosis in PD is still controversial.PC12 cells have been extensively used as a model of catecholaminergic neurons in culture as well as for the study of neuronal apoptotic death. Naive (undifferentiated) PC12 cells grown in the presence of serum undergo apoptosis upon serum withdrawal (9 -11). Furthermore, PC12 cells that become neuronally differentiated and postmitotic following prolonged incubation with NGF undergo apoptosis upon NGF and serum withdrawal (9, 10). Undifferentiated PC12 cell death upon serum withdrawal has been linked to an inappropriate progression through th...

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“…CNTF administration prevents the loss of cholinergic [122], dopaminergic [123], GABA-ergic [124], and thalamocortical [125] neurons. Its encapsulation has been successfully reported in chitosan, alginate, and copolymers in various proportions.…”

Section: Microparticles For Neurotrophic Factor Delivery (Ngf and Cntf)mentioning

confidence: 97%

Brain Drug Delivery Systems for Neurodegenerative Disorders

Garbayo

Ansorena

Blanco-Prieto

2012

CPB

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Neurodegenerative disorders (NDs) are rapidly increasing as population ages. However, successful treatments for NDs have so far been limited and drug delivery to the brain remains one of the major challenges to overcome. There has recently been growing interest in the development of drug delivery systems (DDS) for local or systemic brain administration. DDS are able to improve the pharmacological and therapeutic properties of conventional drugs and reduce their side effects. The present review provides a concise overview of the recent advances made in the field of brain drug delivery for treating neurodegenerative disorders. Examples include polymeric micro and nanoparticles, lipidic nanoparticles, pegylated liposomes, microemulsions and nanogels that have been tested in experimental models of Parkinson's, Alzheimer's and Hungtinton's disease. Overall, the results reviewed here show that DDS have great potential for NDs treatment.

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Ciliary neurotrophic factor prevents degeneration of adult rat substantia nigra dopaminergic neurons in vivo.

Cited by 211 publications

References 49 publications

Ciliary Neurotrophic Factor Mediates Dopamine D₂Receptor-Induced CNS Neurogenesis in Adult Mice

Ciliary Neurotrophic Factor Mediates Dopamine D₂Receptor-Induced CNS Neurogenesis in Adult Mice

Tetrahydrobiopterin Enhances Apoptotic PC12 Cell Death following Withdrawal of Trophic Support

Brain Drug Delivery Systems for Neurodegenerative Disorders

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Ciliary neurotrophic factor prevents degeneration of adult rat substantia nigra dopaminergic neurons in vivo.

Cited by 211 publications

References 49 publications

Ciliary Neurotrophic Factor Mediates Dopamine D2Receptor-Induced CNS Neurogenesis in Adult Mice

Ciliary Neurotrophic Factor Mediates Dopamine D2Receptor-Induced CNS Neurogenesis in Adult Mice

Tetrahydrobiopterin Enhances Apoptotic PC12 Cell Death following Withdrawal of Trophic Support

Brain Drug Delivery Systems for Neurodegenerative Disorders

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Ciliary Neurotrophic Factor Mediates Dopamine D₂Receptor-Induced CNS Neurogenesis in Adult Mice

Ciliary Neurotrophic Factor Mediates Dopamine D₂Receptor-Induced CNS Neurogenesis in Adult Mice