Estrogen protects against dopamine neuron toxicity in primary mesencephalic cultures through an indirect P13K/Akt mediated astrocyte pathway.
Neurosci Lett
; 610: 79-85, 2016 Jan 01.
Article
in En
| MEDLINE
| ID: mdl-26520464
ABSTRACT
Astrocytes regulate neuronal homeostasis and have been implicated in affecting the viability and functioning of surrounding neurons under stressed and injured conditions. Previous data from our lab suggests indirect actions of estrogen through ERα in neighboring astroglia to protect dopamine neurons against 1-methyl-4-phenylpyridinium (MPP(+)) toxicity in mouse mesencephalic cultures. We further evaluate estrogen signaling in astrocytes and the mechanism of estrogen's indirect neuroprotective effects on dopamine neurons. Primary mesencephalic cultures pre-treated with 17ß-estradiol and the membrane impermeable estrogen, E2-BSA, were both neuroprotective against MPP(+) -induced dopamine neuron toxicity, suggesting membrane-initiated neuroprotection. ERα was found in the plasma membrane of astrocyte cultures and colocalized with the lipid raft marker, flotillin-1. A 17ß-estradiol time course revealed a significant increase in Akt, which was inhibited by the PI3 kinase inhibitor, LY294004. Estrogen conditioned media collected from pure astrocyte cultures rescued glial deficient mesencephalic cultures from MPP(+). This indirect estrogen-mediated neuroprotective effect in mesencephalic cultures was significantly reduced when PI3 kinase signaling in astrocytes was blocked prior to collecting estrogen-conditioned media using the irreversible PI3 kinase inhibitor, Wortmannin. Estrogen signaling via astrocytes is rapidly initiated at the membrane level and requires PI3 kinase signaling in order to protect primary mesencephalic dopamine neurons from MPP(+) neurotoxicity.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Astrocytes
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Neuroprotective Agents
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Phosphatidylinositol 3-Kinases
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Estradiol
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Estrogens
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Proto-Oncogene Proteins c-akt
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Dopaminergic Neurons
Limits:
Animals
Language:
En
Journal:
Neurosci Lett
Year:
2016
Document type:
Article