Selective injury to dopaminergic neurons up-regulates GDNF in substantia nigra postnatal cell cultures: Role of neuron–glia crosstalk

Saavedra, Ana; Baltazar, Graça; Santos, Paulo; Carvalho, Caetana M.; Duarte, Emília P.

doi:10.1016/j.nbd.2006.04.008

Cited by 60 publications

(38 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Gene expression profiles, obtained with cDNA microarrays, show GDNF up-regulation in the substantia nigra and striatum after MPTP intoxication (Grunblatt et al, 2001a;Mandel et al, 2002), and in striatal astrocytes from 6-OHDA lesioned rats (Nakagawa and Schwartz, 2004). We have shown that mild damage to dopaminergic neurons in neuron-glia cultures from substantia nigra, but not extensive damage, induces GDNF up-regulation in astrocytes (Saavedra et al, 2006). Since GDNF up-regulation is not observed in cultures previously treated with 6-OHDA, we propose that GDNF induction in astrocytes requires signalling from injured dopaminergic neurons that are still capable of signalling (Saavedra et al, 2006).…”

Section: Gdnf Expression Upon Nigrostriatal Injury: Role Of Neuronglimentioning

confidence: 60%

“…We have shown that mild damage to dopaminergic neurons in neuron-glia cultures from substantia nigra, but not extensive damage, induces GDNF up-regulation in astrocytes (Saavedra et al, 2006). Since GDNF up-regulation is not observed in cultures previously treated with 6-OHDA, we propose that GDNF induction in astrocytes requires signalling from injured dopaminergic neurons that are still capable of signalling (Saavedra et al, 2006).…”

Section: Gdnf Expression Upon Nigrostriatal Injury: Role Of Neuronglimentioning

confidence: 75%

“…GDNF decreases 6-OHDA-induced oxidative stress and reduces the loss of dopamine in the striatum and in the substantia nigra (Smith and Cass, 2007). Moreover, in the presence of a GDNF antibody dopaminergic cell viability decreases in substantia nigra H 2 O 2 -treated cultures, showing that endogenous GDNF up-regulation in response to H 2 O 2 is able to protect dopaminergic neurons in culture (Saavedra et al, 2006). Furthermore, in neuron-glia substantia nigra cell cultures, GDNF up-regulation in response to H 2 O 2 down-regulates the expression of heme oxygenase-1, a marker of oxidative stress (Saavedra et al, 2005).…”

Section: Gdnf From Regulation To Functionmentioning

confidence: 97%

“…In fact, trophic effects of L-DOPA were observed on dopaminergic neurons cocultured with astrocytes (Mena et al, 1997) but, to our knowledge, our group is the only describing the effect of L-DOPA on GDNF levels in the nigrostriatal system. We have shown that L-DOPA induces GDNF up-regulation at the mRNA and protein levels in substantia nigra neuron-glia cell cultures, in a process involving soluble mediators that signal astrocytes to increase GDNF expression (Saavedra et al, 2006). We have also addressed the effect of L-DOPA treatment on GDNF levels in the 6-OHDA rat model of PD.…”

Section: L-dopamentioning

confidence: 99%

“…Role of NF-kB H 2 O 2 increases GDNF mRNA levels in rat astrocytes (Yamagata et al, 2002;Koyama et al, 2003a) and induces GDNF release (Verity et al, 1998;Yamagata et al, 2002). H 2 O 2 also up-regulates GDNF mRNA and protein levels in substantia nigra neuron-glia cell cultures thereby protecting dopaminergic neurons from H 2 O 2 -induced toxicity (Saavedra et al, 2006). These results are consistent with the observation that H 2 O 2 activates the transcription factor NF-kB (Meyer et al, 1993), and with the presence of a binding sequence for NF-kB on GDNF promoter (Woodbury et al, 1998;Baecker et al, 1999;Tanaka et al, 2000).…”

Section: +mentioning

confidence: 99%

See 4 more Smart Citations

Driving GDNF expression: The green and the red traffic lights

Saavedra

Baltazar

Duarte

2008

Progress in Neurobiology

Self Cite

View full text Add to dashboard Cite

Section: Gdnf Expression Upon Nigrostriatal Injury: Role Of Neuronglimentioning

confidence: 60%

Section: Gdnf Expression Upon Nigrostriatal Injury: Role Of Neuronglimentioning

confidence: 75%

Section: Gdnf From Regulation To Functionmentioning

confidence: 97%

Section: L-dopamentioning

confidence: 99%

Section: +mentioning

confidence: 99%

See 3 more Smart Citations

Driving GDNF expression: The green and the red traffic lights

Saavedra

Baltazar

Duarte

2008

Progress in Neurobiology

Self Cite

View full text Add to dashboard Cite

Proteomic profiling of human liver biopsies: Hepatitis C virus–induced fibrosis and mitochondrial dysfunction

Diamond¹,

Jacobs²,

Paeper³

et al. 2007

Hepatology

103

View full text Add to dashboard Cite

Liver biopsies from hepatitis C virus (HCV)-infected patients offer the unique opportunity to study human liver biology and disease in vivo. However, the low protein yields associated with these small samples present a significant challenge for proteomic analysis. In this study we describe the application of an ultrasensitive proteomics platform for performing robust quantitative proteomic studies on microgram amounts of HCV-infected human liver tissue from 15 patients at different stages of fibrosis. A high-quality liver protein database containing 5,920 unique protein identifications supported high throughput quantitative studies using 16 C hronic infection with hepatitis C virus (HCV), a bloodborne pathogen persistently infecting more than 170 million individuals worldwide, often leads to progressive liver disease, including fibrosis, cirrhosis, and hepatocellular carcinoma. 1 Unfortunately, efforts to manage this growing public health problem have been hindered by the lack of an efficient vaccine and limited efficacy of current treatment modalities (for example, interferon and ribavirin therapy). These observations point to the importance of continued efforts to better understand the molecular mechanisms of viral replication and pathogenesis of HCV-associated disease syndromes. To this end, functional genomics technologies have enormous potential to enhance our understanding of virushost interactions, as well as providing practical insights that will impact medical practice. The identification and characterization of altered regulatory pathways is expected to provide new insights into HCV infection biology and new avenues for drug and vaccine development.

show abstract

Glial reactions in Parkinson's disease

2007

View full text Add to dashboard Cite

Dopaminergic neurons of the substantia nigra are particularly vulnerable to oxidative and inflammatory attack. Such processes may play a crucial role in the etiology of Parkinson disease (PD). Since glia are the main generators of these processes, the possibility that PD may be caused by glial dysfunction needs to be considered. This review concentrates on glial reactions in PD. Reactive astrocytes and reactive microglia are abundant in the substantia nigra (SN) of PD cases indicating a robust inflammatory state. Glia normally serve neuroprotective roles but, given adverse stimulation, they may contribute to damaging chronic inflammation. Microglia, the phagocytes of brain, may be the main contributors since they can produce large numbers of superoxide anions and other neurotoxins. Their toxicity towards dopaminergic neurons has been demonstrated in tissue culture and various animal models of PD. The MPTP and ␣-synuclein models are of particular interest. Years after exposure to MPTP, inflammation has been observed in the SN. This has established that an acute insult to the SN can result in a sustained local inflammation. The ␣-synuclein model indicates that an endogenous protein can induce inflammation, and, when overexpressed, can lead to autosomal dominant PD. Less is known about the role of astrocytes than microglia, but they are known to secrete both inflammatory and anti-inflammatory molecules and may play a role in modulating microglial activity. Oligodendrocytes do not seem to play a role in promoting inflammation although, like neurons, they may be damaged by inflammatory processes. Further research concerning glial reactions in PD may lead to disease-modifying therapeutic approaches.

show abstract

Selective injury to dopaminergic neurons up-regulates GDNF in substantia nigra postnatal cell cultures: Role of neuron–glia crosstalk

Cited by 60 publications

References 70 publications

Driving GDNF expression: The green and the red traffic lights

Driving GDNF expression: The green and the red traffic lights

Proteomic profiling of human liver biopsies: Hepatitis C virus–induced fibrosis and mitochondrial dysfunction

Glial reactions in Parkinson's disease

Contact Info

Product

Resources

About