The role of ERK1, 2, and 5 in dopamine neuron survival during aging

Parmar, Mayur; Jaumotte, Juliann D.; Wyrostek, Stephanie L.; Zigmond, Michael J.; Cavanaugh, Jane E.

doi:10.1016/j.neurobiolaging.2013.09.031

Cited by 23 publications

(17 citation statements)

References 53 publications

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“…In a study by Ries et al (2009), the postnatal development of DA neurons of the substantia nigra in vivo was shown to be regulated, at least in part, by the signaling protein Akt/protein kinase B. Similarly, the extracellular signal‐regulated kinase (ERK) pathways have been demonstrated to be important for dopaminergic neuronal development, survival, and function (Cavanaugh et al, 2006a,b; Kim et al, 2006; Yoon et al, 2011; Parmar et al, 2014). For example, using primary dopaminergic mesencephalic cultures, we have shown that pharmacological inhibition of ERK5, and to a lesser extent ERK1 and 2, resulted in a significant loss of viability of dopaminergic neurons at day in vitro (DIV) 2, 4, 6, and 8 (Parmar et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…Similarly, the extracellular signal‐regulated kinase (ERK) pathways have been demonstrated to be important for dopaminergic neuronal development, survival, and function (Cavanaugh et al, 2006a,b; Kim et al, 2006; Yoon et al, 2011; Parmar et al, 2014). For example, using primary dopaminergic mesencephalic cultures, we have shown that pharmacological inhibition of ERK5, and to a lesser extent ERK1 and 2, resulted in a significant loss of viability of dopaminergic neurons at day in vitro (DIV) 2, 4, 6, and 8 (Parmar et al, 2014). Moreover, others have shown that the regulation of dopaminergic neuronal development is regulated by D2 receptor‐mediated ERK activation (Kim et al, 2006; Yoon et al, 2011; Yoon and Baik, 2013).…”

Section: Introductionmentioning

confidence: 99%

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ERK1, 2, and 5 expression and activation in dopaminergic brain regions during postnatal development

Parmar

Jaumotte

Zigmond

et al. 2015

Intl J of Devlp Neuroscience

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Degeneration and dysfunctioning of dopaminergic neurons in the midbrain have been associated with serious neurodegenerative and neuropsychiatric disorders. Elucidating the underlying neurobiology of these neurons during early postnatal development may provide important information regarding the etiology of these disorders. Cellular signaling pathways have been shown to regulate postnatal neuronal development. Among several signaling pathways, extracellular-regulated mitogen kinases (ERK) 1, 2, and 5 have been shown to be crucial for the survival and function of dopaminergic neurons. In this study, the basal expression and activation of ERK1, 2, and 5 were studied during postnatal development in regions rich in DA cells and terminals. In the striatum (STR) and ventral mesencephalon regions of the substantia nigra (SN) and ventral tegmental area (VTA), ERK5 expression and activation were high during early postnatal days and declined with aging. Interestingly, sharp increases in phosphorylated or activated ERK1 and ERK2 were observed at postnatal day (PND) 7 in the SN and VTA. In contrast, in the STR, the levels of phosphorylated ERK1 and 2 were significantly higher at PND0 than at any other PND examined. Overall, the understanding of alterations in ERK signaling in regions rich in DA cells and DA terminals during postnatal neuronal development may provide information about their role in regulation of dopamine neuronal development which may ultimately provide insight into the underlying mechanisms of dopamine neurodegeneration.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

ERK1, 2, and 5 expression and activation in dopaminergic brain regions during postnatal development

Parmar

Jaumotte

Zigmond

et al. 2015

Intl J of Devlp Neuroscience

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“…The cell culture technique widely used for deriving neuronal cultures is the conventional monolayer [Yasuhara et al, 2006;Fasano et al, 2008;Mosharov et al, 2009;Babu et al, 2011;Walker et al, 2013;Walker and Kempermann, 2014]. The major limitation of this technique is that the neuron-glia ratio does not replicate the in vivo brain region, along with the low yields of specialized neuronal cells such as dopaminergic neurons [McNaught and Jenner, 1999;Fasano et al, 2008;Tolosa et al, 2013;Parmar et al, 2014;Brzozowski et al, 2015;Weinert et al, 2015]. This is probably because in a 2D format in vivo cell-cell interactions are limited, affecting the yield of neuronal and glial cells [Pardo and Honegger, 2000;Cukierman et al, 2002;Pampaloni et al, 2007;Justice et al, 2009].…”

Section: Introductionmentioning

confidence: 99%

“…It appears that 2D monolayer primary midbrain culture results in either a very low yield (2-5%) of dopaminergic neurons or a reduced survival of these neurons in culture [Hyman et al, 1991;Fawcett et al, 1995;Fasano et al, 2008;Tolosa et al, 2013;Gaven et al, 2014;Parmar et al, 2014;Brzozowski et al, 2015;Weinert et al, 2015]. Certain other protocols have shown a yield as high as 40-90% of TH neurons in culture [Collier et al, 1990;Shimoda et al, 1992;Studer et al, 2000]; however, these yields do not reflect the in vivo situation.…”

Section: Introductionmentioning

confidence: 99%

By Changing Dimensionality, Sequential Culturing of Midbrain Cells, rather than Two-Dimensional Culture, Generates a Neuron-Glia Ratio Closer to in vivo Adult Midbrain

Ganapathy¹,

Sowmithra²,

Bhonde³

2016

Cells Tissues Organs

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The neuron-glia ratio is of prime importance for maintaining the physiological homeostasis of neuronal and glial cells, and especially crucial for dopaminergic neurons because a reduction in glial density has been reported in postmortem reports of brains affected by Parkinson's disease. We thus aimed at developing an in vitro midbrain culture which would replicate a similar neuron-glia ratio to that in in vivo adult midbrain while containing a similar number of dopaminergic neurons. A sequential culture technique was adopted to achieve this. Neural progenitors (NPs) were generated by the hanging-drop method and propagated as 3D neurospheres followed by the derivation of outgrowth from these neurospheres on a chosen extracellular matrix. The highest proliferation was observed in neurospheres from day in vitro (DIV) 5 through MTT and FACS analysis of Ki67 expression. FACS analysis using annexin/propidium iodide showed an increase in the apoptotic population from DIV 8. DIV 5 neurospheres were therefore selected for deriving the differentiated outgrowth of midbrain on a poly-L-lysine-coated surface. Quantitative RT-PCR showed comparable gene expressions of the mature neuronal marker β-tubulin III, glial marker GFAP and dopaminergic marker tyrosine hydroxylase (TH) as compared to in vivo adult rat midbrain. The FACS analysis showed a similar neuron-glia ratio obtained by the sequential culture in comparison to adult rat midbrain. The yield of β-tubulin III and TH was distinctly higher in the sequential culture in comparison to 2D culture, which showed a higher yield of GFAP immunopositive cells. Functional characterization indicated that both the constitutive and inducible (KCl and ATP) release of dopamine was distinctly higher in the sequential culture than the 2D culture. Thus, the sequential culture technique succeeded in the initial enrichment of NPs in 3D neurospheres, which in turn resulted in an optimal attainment of the neuron-glia ratio on outgrowth culture from these neurospheres.

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“…In the nervous system, MAP2K/MAPK pathways are associated with neuronal cell death (Subramaniam et al 2004;Subramaniam and Unsicker 2010) and survival (Wang et al 2005;Cavanaugh et al 2006;Parmar et al 2014), as well as with neuropathic pain (Ma and Quirion 2005). In particular, MAPK7 has been implicated in neuronal survival and death (Cavanaugh 2004;Subramaniam et al 2004).…”

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confidence: 99%

Yeast genetic interaction screen of human genes associated with amyotrophic lateral sclerosis: identification of MAP2K5 kinase as a potential drug target

Chung

Yachie

et al. 2017

Genome Res.

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The role of ERK1, 2, and 5 in dopamine neuron survival during aging

Cited by 23 publications

References 53 publications

ERK1, 2, and 5 expression and activation in dopaminergic brain regions during postnatal development

ERK1, 2, and 5 expression and activation in dopaminergic brain regions during postnatal development

By Changing Dimensionality, Sequential Culturing of Midbrain Cells, rather than Two-Dimensional Culture, Generates a Neuron-Glia Ratio Closer to in vivo Adult Midbrain

Yeast genetic interaction screen of human genes associated with amyotrophic lateral sclerosis: identification of MAP2K5 kinase as a potential drug target

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