Pgrmc1/BDNF signaling plays a critical role in mediating glia-neuron cross talk

Fen Sun, Trinh Nguyen, Xin Jin, Ren-Qi Huang, Zhenglan Chen, Rebecca Lynn Cunningham, Meharvan Singh, Chang Su

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

Abstract

Progesterone (P4) exerts robust cytoprotection in brain slice cultures (containing both neurons and glia), yet such protection is not as evident in neuron-enriched cultures, suggesting that glia may play an indispensable role in P4's neuroprotection. We previously reported that a membraneassociated P4 receptor, P4 receptor membrane component 1, mediates P4-induced brain-derived neurotrophic factor (BDNF) release from glia. Here, we sought to determine whether glia are required for P4's neuroprotection and whether glia's roles are mediated, at least partially, via releasing soluble factors to act on neighboring neurons. Our data demonstrate that P4 increased the level of mature BDNF (neuroprotective) while decreasing pro-BDNF (potentially neurotoxic) in the conditioned media (CMs) of cultured C6 astrocytes. We examined the effects of CMs derived from P4-treated astrocytes (P4-CMs) on 2 neuronal models: 1) all-trans retinoid acid-differentiated SH-SY5Y cells and 2) mouse primary hippocampal neurons. P4-CM increased synaptic marker expression and promoted neuronal survival against H2O2. These effects were attenuated by Y1036 (an inhibitor of neurotrophin receptor [tropomysin-related kinase] signaling), as well as tropomysin-related kinase B-IgG (a more specific inhibitor to block BDNF signaling), which pointed to BDNF as the key protective component within P4-CM. These findings suggest that P4 may exert its maximal protection by triggering a glia-neuron cross talk, in which P4 promotes mature BDNF release from glia to enhance synaptogenesis as well as survival of neurons. This recognition of the importance of glia in mediating P4's neuroprotection may also inform the design of effective therapeutic methods for treating diseases wherein neuronal death and/or synaptic deficits are noted.

Original languageEnglish
Pages (from-to)2067-2079
Number of pages13
JournalEndocrinology
Volume157
Issue number5
DOIs
StatePublished - 1 May 2016

Fingerprint

Brain-Derived Neurotrophic Factor
Neuroglia
Neurons
Conditioned Culture Medium
Astrocytes
Phosphotransferases
Nerve Growth Factor Receptors
Cytoprotection
Retinoids
Progesterone
Immunoglobulin G
Acids
Membranes
Brain

Cite this

Sun, Fen ; Nguyen, Trinh ; Jin, Xin ; Huang, Ren-Qi ; Chen, Zhenglan ; Cunningham, Rebecca Lynn ; Singh, Meharvan ; Su, Chang. / Pgrmc1/BDNF signaling plays a critical role in mediating glia-neuron cross talk. In: Endocrinology. 2016 ; Vol. 157, No. 5. pp. 2067-2079.
@article{cd0acc6c5b104b2799ae3a5765bf3523,
title = "Pgrmc1/BDNF signaling plays a critical role in mediating glia-neuron cross talk",
abstract = "Progesterone (P4) exerts robust cytoprotection in brain slice cultures (containing both neurons and glia), yet such protection is not as evident in neuron-enriched cultures, suggesting that glia may play an indispensable role in P4's neuroprotection. We previously reported that a membraneassociated P4 receptor, P4 receptor membrane component 1, mediates P4-induced brain-derived neurotrophic factor (BDNF) release from glia. Here, we sought to determine whether glia are required for P4's neuroprotection and whether glia's roles are mediated, at least partially, via releasing soluble factors to act on neighboring neurons. Our data demonstrate that P4 increased the level of mature BDNF (neuroprotective) while decreasing pro-BDNF (potentially neurotoxic) in the conditioned media (CMs) of cultured C6 astrocytes. We examined the effects of CMs derived from P4-treated astrocytes (P4-CMs) on 2 neuronal models: 1) all-trans retinoid acid-differentiated SH-SY5Y cells and 2) mouse primary hippocampal neurons. P4-CM increased synaptic marker expression and promoted neuronal survival against H2O2. These effects were attenuated by Y1036 (an inhibitor of neurotrophin receptor [tropomysin-related kinase] signaling), as well as tropomysin-related kinase B-IgG (a more specific inhibitor to block BDNF signaling), which pointed to BDNF as the key protective component within P4-CM. These findings suggest that P4 may exert its maximal protection by triggering a glia-neuron cross talk, in which P4 promotes mature BDNF release from glia to enhance synaptogenesis as well as survival of neurons. This recognition of the importance of glia in mediating P4's neuroprotection may also inform the design of effective therapeutic methods for treating diseases wherein neuronal death and/or synaptic deficits are noted.",
author = "Fen Sun and Trinh Nguyen and Xin Jin and Ren-Qi Huang and Zhenglan Chen and Cunningham, {Rebecca Lynn} and Meharvan Singh and Chang Su",
year = "2016",
month = "5",
day = "1",
doi = "10.1210/en.2015-1610",
language = "English",
volume = "157",
pages = "2067--2079",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "Oxford University Press",
number = "5",

}

Pgrmc1/BDNF signaling plays a critical role in mediating glia-neuron cross talk. / Sun, Fen; Nguyen, Trinh; Jin, Xin; Huang, Ren-Qi; Chen, Zhenglan; Cunningham, Rebecca Lynn; Singh, Meharvan; Su, Chang.

In: Endocrinology, Vol. 157, No. 5, 01.05.2016, p. 2067-2079.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Pgrmc1/BDNF signaling plays a critical role in mediating glia-neuron cross talk

AU - Sun, Fen

AU - Nguyen, Trinh

AU - Jin, Xin

AU - Huang, Ren-Qi

AU - Chen, Zhenglan

AU - Cunningham, Rebecca Lynn

AU - Singh, Meharvan

AU - Su, Chang

PY - 2016/5/1

Y1 - 2016/5/1

N2 - Progesterone (P4) exerts robust cytoprotection in brain slice cultures (containing both neurons and glia), yet such protection is not as evident in neuron-enriched cultures, suggesting that glia may play an indispensable role in P4's neuroprotection. We previously reported that a membraneassociated P4 receptor, P4 receptor membrane component 1, mediates P4-induced brain-derived neurotrophic factor (BDNF) release from glia. Here, we sought to determine whether glia are required for P4's neuroprotection and whether glia's roles are mediated, at least partially, via releasing soluble factors to act on neighboring neurons. Our data demonstrate that P4 increased the level of mature BDNF (neuroprotective) while decreasing pro-BDNF (potentially neurotoxic) in the conditioned media (CMs) of cultured C6 astrocytes. We examined the effects of CMs derived from P4-treated astrocytes (P4-CMs) on 2 neuronal models: 1) all-trans retinoid acid-differentiated SH-SY5Y cells and 2) mouse primary hippocampal neurons. P4-CM increased synaptic marker expression and promoted neuronal survival against H2O2. These effects were attenuated by Y1036 (an inhibitor of neurotrophin receptor [tropomysin-related kinase] signaling), as well as tropomysin-related kinase B-IgG (a more specific inhibitor to block BDNF signaling), which pointed to BDNF as the key protective component within P4-CM. These findings suggest that P4 may exert its maximal protection by triggering a glia-neuron cross talk, in which P4 promotes mature BDNF release from glia to enhance synaptogenesis as well as survival of neurons. This recognition of the importance of glia in mediating P4's neuroprotection may also inform the design of effective therapeutic methods for treating diseases wherein neuronal death and/or synaptic deficits are noted.

AB - Progesterone (P4) exerts robust cytoprotection in brain slice cultures (containing both neurons and glia), yet such protection is not as evident in neuron-enriched cultures, suggesting that glia may play an indispensable role in P4's neuroprotection. We previously reported that a membraneassociated P4 receptor, P4 receptor membrane component 1, mediates P4-induced brain-derived neurotrophic factor (BDNF) release from glia. Here, we sought to determine whether glia are required for P4's neuroprotection and whether glia's roles are mediated, at least partially, via releasing soluble factors to act on neighboring neurons. Our data demonstrate that P4 increased the level of mature BDNF (neuroprotective) while decreasing pro-BDNF (potentially neurotoxic) in the conditioned media (CMs) of cultured C6 astrocytes. We examined the effects of CMs derived from P4-treated astrocytes (P4-CMs) on 2 neuronal models: 1) all-trans retinoid acid-differentiated SH-SY5Y cells and 2) mouse primary hippocampal neurons. P4-CM increased synaptic marker expression and promoted neuronal survival against H2O2. These effects were attenuated by Y1036 (an inhibitor of neurotrophin receptor [tropomysin-related kinase] signaling), as well as tropomysin-related kinase B-IgG (a more specific inhibitor to block BDNF signaling), which pointed to BDNF as the key protective component within P4-CM. These findings suggest that P4 may exert its maximal protection by triggering a glia-neuron cross talk, in which P4 promotes mature BDNF release from glia to enhance synaptogenesis as well as survival of neurons. This recognition of the importance of glia in mediating P4's neuroprotection may also inform the design of effective therapeutic methods for treating diseases wherein neuronal death and/or synaptic deficits are noted.

UR - http://www.scopus.com/inward/record.url?scp=84969816019&partnerID=8YFLogxK

U2 - 10.1210/en.2015-1610

DO - 10.1210/en.2015-1610

M3 - Article

VL - 157

SP - 2067

EP - 2079

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 5

ER -