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The MAPK and PI3K pathways mediate CNTF-induced neuronal survival and process outgrowth in hypothalamic organotypic cultures.

Askvig JM, Watt JA - J Cell Commun Signal (2015)

Bottom Line: Our results demonstrate that the MAPK-ERK½ pathway mediates CNTF-induced neuronal survival.We also provide quantitative evidence indicating that CNTF promotes process outgrowth of OT neurons via the PI3K-AKT pathway.Together, these data indicate that distinct intracellular signaling pathways mediate diverse neuroprotective processes in response to CNTF.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Concordia College, Moorhead, MN, 56562, USA. jaskvig@cord.edu.

ABSTRACT
While collateral sprouting has been shown to occur in a variety of neuronal populations, the factor or factors responsible for mediating the sprouting response remain largely un-defined. There is evidence indicating that ciliary neurotrophic factor (CNTF) may play an important role in promoting neuronal survival and process outgrowth in neuronal phenotypes tested to date. We previously demonstrated that the astrocytic Jak-STAT pathway is necessary to mediate CNTF-induced oxytocinergic (OT) neuronal survival; however, the mechanism (s) of CNTF-mediated process outgrowth remain unknown. Our working hypothesis is that CNTF mediates differential neuroprotective responses via different intracellular signal transduction pathways. In order to test this hypothesis, we utilized stationary hypothalamic organotypic cultures to assess the contribution of the MAPK-ERK and PI3-AKT pathways to OT neuron survival and process outgrowth. Our results demonstrate that the MAPK-ERK½ pathway mediates CNTF-induced neuronal survival. Moreover, we show that inhibition of the p38-, JNK-MAPK, and mTOR pathways prevents loss OT neurons following axotomy. We also provide quantitative evidence indicating that CNTF promotes process outgrowth of OT neurons via the PI3K-AKT pathway. Together, these data indicate that distinct intracellular signaling pathways mediate diverse neuroprotective processes in response to CNTF.

No MeSH data available.


The MAPK-ERK½ pathway is necessary to mediate the CNTF-induced survival of OT neurons. Immunohistochemical neuronal cell counts demonstrated that exogenous rrCNTF promoted the survival of OT neurons (SON: p < 0.0001; PVN: p < 0.0001) compared to control, while inhibition of the MAPK-ERK½ pathway with U0126 (SON: p < 0.0001; PVN: p < 0.0001), PD98059 (SON: p < 0.0001; PVN: p < 0.0001), and PD184352 (SON: p < 0.0001; PVN: p < 0.0001) significantly reduced the number of surviving OT neurons in the SON (a) and PVN (b) compared to the 25 ng/ml rrCNTF group. Column bars and error bars represent the mean and SD of [n] groups. PVN, paraventricular nucleus; SON, supraoptic nucleus. ***p < 0.0001
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Fig1: The MAPK-ERK½ pathway is necessary to mediate the CNTF-induced survival of OT neurons. Immunohistochemical neuronal cell counts demonstrated that exogenous rrCNTF promoted the survival of OT neurons (SON: p < 0.0001; PVN: p < 0.0001) compared to control, while inhibition of the MAPK-ERK½ pathway with U0126 (SON: p < 0.0001; PVN: p < 0.0001), PD98059 (SON: p < 0.0001; PVN: p < 0.0001), and PD184352 (SON: p < 0.0001; PVN: p < 0.0001) significantly reduced the number of surviving OT neurons in the SON (a) and PVN (b) compared to the 25 ng/ml rrCNTF group. Column bars and error bars represent the mean and SD of [n] groups. PVN, paraventricular nucleus; SON, supraoptic nucleus. ***p < 0.0001

Mentions: Our results indicate that treatment of organotypic cultures with rrCNTF, (25 ng/ml, 14 days) (Askvig et al. 2013), resulted in a 443 % increase in the number of surviving OT neurons in the SON when compared with control values obtained from cultures maintained in rrCNTF-free media (Fig. 1a). Additionally, a significant 52 % increase in OT neuronal survival was also observed in the PVN (Fig. 1b).Fig. 1


The MAPK and PI3K pathways mediate CNTF-induced neuronal survival and process outgrowth in hypothalamic organotypic cultures.

Askvig JM, Watt JA - J Cell Commun Signal (2015)

The MAPK-ERK½ pathway is necessary to mediate the CNTF-induced survival of OT neurons. Immunohistochemical neuronal cell counts demonstrated that exogenous rrCNTF promoted the survival of OT neurons (SON: p < 0.0001; PVN: p < 0.0001) compared to control, while inhibition of the MAPK-ERK½ pathway with U0126 (SON: p < 0.0001; PVN: p < 0.0001), PD98059 (SON: p < 0.0001; PVN: p < 0.0001), and PD184352 (SON: p < 0.0001; PVN: p < 0.0001) significantly reduced the number of surviving OT neurons in the SON (a) and PVN (b) compared to the 25 ng/ml rrCNTF group. Column bars and error bars represent the mean and SD of [n] groups. PVN, paraventricular nucleus; SON, supraoptic nucleus. ***p < 0.0001
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4580676&req=5

Fig1: The MAPK-ERK½ pathway is necessary to mediate the CNTF-induced survival of OT neurons. Immunohistochemical neuronal cell counts demonstrated that exogenous rrCNTF promoted the survival of OT neurons (SON: p < 0.0001; PVN: p < 0.0001) compared to control, while inhibition of the MAPK-ERK½ pathway with U0126 (SON: p < 0.0001; PVN: p < 0.0001), PD98059 (SON: p < 0.0001; PVN: p < 0.0001), and PD184352 (SON: p < 0.0001; PVN: p < 0.0001) significantly reduced the number of surviving OT neurons in the SON (a) and PVN (b) compared to the 25 ng/ml rrCNTF group. Column bars and error bars represent the mean and SD of [n] groups. PVN, paraventricular nucleus; SON, supraoptic nucleus. ***p < 0.0001
Mentions: Our results indicate that treatment of organotypic cultures with rrCNTF, (25 ng/ml, 14 days) (Askvig et al. 2013), resulted in a 443 % increase in the number of surviving OT neurons in the SON when compared with control values obtained from cultures maintained in rrCNTF-free media (Fig. 1a). Additionally, a significant 52 % increase in OT neuronal survival was also observed in the PVN (Fig. 1b).Fig. 1

Bottom Line: Our results demonstrate that the MAPK-ERK½ pathway mediates CNTF-induced neuronal survival.We also provide quantitative evidence indicating that CNTF promotes process outgrowth of OT neurons via the PI3K-AKT pathway.Together, these data indicate that distinct intracellular signaling pathways mediate diverse neuroprotective processes in response to CNTF.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Concordia College, Moorhead, MN, 56562, USA. jaskvig@cord.edu.

ABSTRACT
While collateral sprouting has been shown to occur in a variety of neuronal populations, the factor or factors responsible for mediating the sprouting response remain largely un-defined. There is evidence indicating that ciliary neurotrophic factor (CNTF) may play an important role in promoting neuronal survival and process outgrowth in neuronal phenotypes tested to date. We previously demonstrated that the astrocytic Jak-STAT pathway is necessary to mediate CNTF-induced oxytocinergic (OT) neuronal survival; however, the mechanism (s) of CNTF-mediated process outgrowth remain unknown. Our working hypothesis is that CNTF mediates differential neuroprotective responses via different intracellular signal transduction pathways. In order to test this hypothesis, we utilized stationary hypothalamic organotypic cultures to assess the contribution of the MAPK-ERK and PI3-AKT pathways to OT neuron survival and process outgrowth. Our results demonstrate that the MAPK-ERK½ pathway mediates CNTF-induced neuronal survival. Moreover, we show that inhibition of the p38-, JNK-MAPK, and mTOR pathways prevents loss OT neurons following axotomy. We also provide quantitative evidence indicating that CNTF promotes process outgrowth of OT neurons via the PI3K-AKT pathway. Together, these data indicate that distinct intracellular signaling pathways mediate diverse neuroprotective processes in response to CNTF.

No MeSH data available.