Reduced BDNF mRNA Expression in the Parkinson's Disease Substantia Nigra

Howells, David W.; Porritt, Michelle J.; Wong, J; Batchelor, Peter; Kalnins, R.; Hughes, Andrew; Donnan, Geoffrey A.

doi:10.1006/exnr.2000.7483

Cited by 417 publications

(276 citation statements)

References 42 publications

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“…Although current therapy for Parkinson's disease focuses on symptomatic relief, there is a great need to identify neuroprotective therapies that will slow disease progression. There is reduced expression of various neurotrophic factors, including brain-derived neurotrophic factor, basic fibroblast growth factor (bFGF), glial-derived neurotrophic factor (GDNF), and ciliary neurotrophic factor, in Parkinson's disease brains (Tooyama et al, 1993;Howells et al, 2000;Siegel and Chauhan, 2000), suggesting a role for decreased neurotrophic signaling in degeneration of dopaminergic neurons. The elucidation of downstream mechanisms for trophic factor neuroprotection may identify new drug targets for Parkinson's disease therapy.…”

Section: Introductionmentioning

confidence: 99%

Basic Fibroblast Growth Factor Protects against Rotenone-Induced Dopaminergic Cell Death through Activation of Extracellular Signal-Regulated Kinases 1/2 and Phosphatidylinositol-3 Kinase Pathways

Hsuan¹,

Klintworth²,

Xia³

2006

J. Neurosci.

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Administration of rotenone to rats reproduces many features of Parkinson's disease, including dopaminergic neuron degeneration, and provides a useful model to study the pathogenesis of Parkinson's disease. However, the cell death mechanisms induced by rotenone and potential neuroprotective mechanisms against rotenone are not well defined. Here we report that rotenone-induced apoptosis in human dopaminergic SH-SY5Y cells is attenuated by pretreatment with several growth factors, most notably basic fibroblast growth factor (bFGF). bFGF activated both extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphatidylinositol-3 kinase (PI3-kinase) pathways in SH-SY5Y cells. Ectopic activation of ERK1/2 or PI3-kinase protected against rotenone, whereas inhibition of either pathway attenuated bFGF protection. Reducing the expression of the proapoptotic protein Bcl-2-associated death protein (BAD) by small interfering RNA rendered SH-SY5Y cells resistant to rotenone, implicating BAD in rotenone-induced cell death. Interestingly, bFGF induced a long-lasting phosphorylation of BAD at serine 112, suggesting BAD inactivation through the ERK1/2 signaling pathway. Moreover, primary cultured dopaminergic neurons from mesencephalon were more sensitive to rotenone-induced cell death than nondopaminergic neurons in the same culture. The loss of dopaminergic neurons was blocked by bFGF, an inhibition dependent on ERK1/2 and PI3-kinase signaling. These data suggest that rotenone-induced dopaminergic cell death requires BAD and identify bFGF and its activation of ERK1/2 and PI3-kinase signaling pathways as novel intervention strategies to block cell death in the rotenone model of Parkinson's disease.

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Section: Introductionmentioning

confidence: 99%

Basic Fibroblast Growth Factor Protects against Rotenone-Induced Dopaminergic Cell Death through Activation of Extracellular Signal-Regulated Kinases 1/2 and Phosphatidylinositol-3 Kinase Pathways

Hsuan¹,

Klintworth²,

Xia³

2006

J. Neurosci.

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“…Preclinical evidence is corroborated by clinical reports revealing that nigrostriatal dopamine neurons of PD patients show markedly decreased levels of BDNF [14][15][16][17] confirming that reduced amount of the neurotrophin may be involved in the etiology and pathogenesis of PD.…”

mentioning

confidence: 72%

Shedding light into the role of BDNF in the pharmacotherapy of Parkinson's disease

Fumagalli¹,

Racagni

Riva³

2006

Pharmacogenomics J

117

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Parkinson's disease (PD) is a chronic, neurodegenerative disease with a 1% incidence in the population over 55 years of age. Movement impairments represent undoubtedly the hallmark of the disorder; however, extensive evidence implicates cognitive deficits as concomitant peculiar features. Brainderived neurotrophic factor (BDNF) colocalizes with dopamine neurons in the substantia nigra, where dopaminergic cell bodies are located, and it has recently garnered attention as a molecule crucial for cognition, a function that is also compromised in PD patients. Thus, due to its colocalization with dopaminergic neurons and its role in cognition, BDNF might possess a dual role in PD, both as a neuroprotective molecule, since its inhibition leads to loss of nigral dopaminergic neurons, and as a neuromodulator, as its enhanced expression ameliorates cognitive processes. In this review, we discuss the mechanism of action of established as well as novel drugs for PD with a particular emphasis to those interfering with BDNF biosynthesis.

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“…Altered levels of BDNF and its receptor, Tropomyosin receptor kinase B (TrkB) in the entorhinal cortex (EC) and the frontal cortex (FC) are related to impairments in memory and cognition associated with AD [95], Down Syndrome [96], and aging [97]. PD is associated with reduced BDNF levels at both the transcript and protein levels in the dopaminergic neurons of the substantia nigra [98]. Similarly, in Huntington's disease, hampering the transport of BDNF from the cortical to the striatal neurons results in the loss of striatal neurons and impairments in the voluntary muscle movements [99].…”

Section: Neurochemicals Behaviours and Psychiatric Perspectives Of Nmentioning

confidence: 99%

Neurochemicals, Behaviours and Psychiatric Perspectives of Neurological Diseases

Choudhury¹,

Sahu²,

Ramanujam³

et al. 2018

Neuropsychiatry

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Structural changes in different regions of the brain have become clinically relevant and regarded as the signature phenomenon for neurological diseases. Morphological changes in brain are also associated with neuronal and neurochemical alterations. Studies have showed that minute changes in neurochemical levels may have marked impact on the psychobehaviour of the subject. Several neurological disease profiles have been reported with such specific psychobehavioural expression. However, application of behavioural abnormalities as possible disease progress markers has not been considered and emphasised much. Reports suggested that-the subjects, who have already entered into the terminal stage of the disease, used to show cardinal behavioural signs for a specific disease profile. However, psychological expressions are comparatively early expressive. As most of the neurodegenerative disorders are unidirectional and progressive by nature, therapeutic intervention at the right time is essential for attaining the desired outcome. Moreover, early diagnosis can aid in managing the disease progression also. Psychobehavioural analysis could meet the expected outcome of disease diagnosis if implemented properly and timely. In the present review, we have amalgamated the reported behavioural anomalies with the supportive background from neurochemical basis. Further, we have concluded that behaviour centric studies could be a potential diagnostic tool for the early diagnosis of major neurological diseases such as Alzheimer disease, Parkinson's disease, Amyotrophic lateral sclerosis (ALS), Bipolar disorder, Schizophrenia, Impulse control disorder (ICD) and Obsessive-compulsive disorder (OCD).

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Reduced BDNF mRNA Expression in the Parkinson's Disease Substantia Nigra

Cited by 417 publications

References 42 publications

Basic Fibroblast Growth Factor Protects against Rotenone-Induced Dopaminergic Cell Death through Activation of Extracellular Signal-Regulated Kinases 1/2 and Phosphatidylinositol-3 Kinase Pathways

Basic Fibroblast Growth Factor Protects against Rotenone-Induced Dopaminergic Cell Death through Activation of Extracellular Signal-Regulated Kinases 1/2 and Phosphatidylinositol-3 Kinase Pathways

Shedding light into the role of BDNF in the pharmacotherapy of Parkinson's disease

Neurochemicals, Behaviours and Psychiatric Perspectives of Neurological Diseases

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