Possible neuroprotective property of nicotinic acetylcholine receptors in association with predominant upregulation of glial cell line-derived neurotrophic factor in astrocytes

Takeshi Takarada, Noritaka Nakamichi, Hirofumi Kawagoe, Masato Ogura, Ryo Fukumori, Ryota Nakazato, Koichi Fujikawa, Miki Kou, Yukio Yoneda

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The underlying mechanisms are still unclear for the neuroprotective properties of nicotine to date, whereas we have shown functional expression of nicotinic acetylcholine receptors (nAChRs) responsible for the influx of extracellular Ca2+ in cultured rat cortical astrocytes. In this study, we investigated the possible involvement of astrocytic nAChRs in the neuroprotection by this agonist. Exposure to nicotine predominantly induced mRNA expression of glial cell line-derived neurotrophic factor (GDNF) among the different neurotrophic factors examined in cultured astrocytes, in a manner sensitive to nAChR antagonists, nifedipine, and aCa2+ chelator. Nicotine significantly increased GDNF in a concentration-dependent manner in cultured astrocytes but not in neurons or neural progenitors even at the highest concentration used. In cultured astrocytes, a transient increase was seen in the expression of mRNA and corresponding protein for GDNF during sustained exposure to nicotine for 24 hr. Cytotoxicity mediated by oxidative, calcium, mitochondrial, or endoplasmic reticulum stress was invariably protected against in cortical neurons cultured with conditioned medium from astrocytes previously exposed to nicotine, and preincubation with the anti-GDNF antibody reduced the neuroprotection by conditioned medium from astrocytes exposed to nicotine. Intraperitoneal administration of nicotine transiently increased the number of cells immunoreactive for both GDNF and glial fibrillary acidic protein in rat cerebral cortex. These results suggest that astrocytic nAChRs play a role in the neuroprotection against different cytotoxins after predominant upregulation of GDNF expression through a mechanism relevant to the acceleration of extracellular Ca2+ influx in rat brain in a particular situation.

Original languageEnglish
Pages (from-to)2074-2085
Number of pages12
JournalJournal of Neuroscience Research
Volume90
Issue number11
DOIs
Publication statusPublished - Nov 2012
Externally publishedYes

Fingerprint

Glial Cell Line-Derived Neurotrophic Factor
Nicotinic Receptors
Nicotine
Astrocytes
Up-Regulation
Conditioned Culture Medium
Neurons
Messenger RNA
Endoplasmic Reticulum Stress
Glial Fibrillary Acidic Protein
Cytotoxins
Nerve Growth Factors
Nifedipine
Chelating Agents
Cerebral Cortex
Cell Count
Calcium
Antibodies
Brain

Keywords

  • Astrocytes
  • GDNF
  • NAChR
  • Neuroprotection
  • Nicotine

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Possible neuroprotective property of nicotinic acetylcholine receptors in association with predominant upregulation of glial cell line-derived neurotrophic factor in astrocytes. / Takarada, Takeshi; Nakamichi, Noritaka; Kawagoe, Hirofumi; Ogura, Masato; Fukumori, Ryo; Nakazato, Ryota; Fujikawa, Koichi; Kou, Miki; Yoneda, Yukio.

In: Journal of Neuroscience Research, Vol. 90, No. 11, 11.2012, p. 2074-2085.

Research output: Contribution to journalArticle

Takarada, Takeshi ; Nakamichi, Noritaka ; Kawagoe, Hirofumi ; Ogura, Masato ; Fukumori, Ryo ; Nakazato, Ryota ; Fujikawa, Koichi ; Kou, Miki ; Yoneda, Yukio. / Possible neuroprotective property of nicotinic acetylcholine receptors in association with predominant upregulation of glial cell line-derived neurotrophic factor in astrocytes. In: Journal of Neuroscience Research. 2012 ; Vol. 90, No. 11. pp. 2074-2085.
@article{ea475d5a6e404aed88b96c0a500ea48c,
title = "Possible neuroprotective property of nicotinic acetylcholine receptors in association with predominant upregulation of glial cell line-derived neurotrophic factor in astrocytes",
abstract = "The underlying mechanisms are still unclear for the neuroprotective properties of nicotine to date, whereas we have shown functional expression of nicotinic acetylcholine receptors (nAChRs) responsible for the influx of extracellular Ca2+ in cultured rat cortical astrocytes. In this study, we investigated the possible involvement of astrocytic nAChRs in the neuroprotection by this agonist. Exposure to nicotine predominantly induced mRNA expression of glial cell line-derived neurotrophic factor (GDNF) among the different neurotrophic factors examined in cultured astrocytes, in a manner sensitive to nAChR antagonists, nifedipine, and aCa2+ chelator. Nicotine significantly increased GDNF in a concentration-dependent manner in cultured astrocytes but not in neurons or neural progenitors even at the highest concentration used. In cultured astrocytes, a transient increase was seen in the expression of mRNA and corresponding protein for GDNF during sustained exposure to nicotine for 24 hr. Cytotoxicity mediated by oxidative, calcium, mitochondrial, or endoplasmic reticulum stress was invariably protected against in cortical neurons cultured with conditioned medium from astrocytes previously exposed to nicotine, and preincubation with the anti-GDNF antibody reduced the neuroprotection by conditioned medium from astrocytes exposed to nicotine. Intraperitoneal administration of nicotine transiently increased the number of cells immunoreactive for both GDNF and glial fibrillary acidic protein in rat cerebral cortex. These results suggest that astrocytic nAChRs play a role in the neuroprotection against different cytotoxins after predominant upregulation of GDNF expression through a mechanism relevant to the acceleration of extracellular Ca2+ influx in rat brain in a particular situation.",
keywords = "Astrocytes, GDNF, NAChR, Neuroprotection, Nicotine",
author = "Takeshi Takarada and Noritaka Nakamichi and Hirofumi Kawagoe and Masato Ogura and Ryo Fukumori and Ryota Nakazato and Koichi Fujikawa and Miki Kou and Yukio Yoneda",
year = "2012",
month = "11",
doi = "10.1002/jnr.23101",
language = "English",
volume = "90",
pages = "2074--2085",
journal = "Journal of Neuroscience Research",
issn = "0360-4012",
publisher = "Wiley-Liss Inc.",
number = "11",

}

TY - JOUR

T1 - Possible neuroprotective property of nicotinic acetylcholine receptors in association with predominant upregulation of glial cell line-derived neurotrophic factor in astrocytes

AU - Takarada, Takeshi

AU - Nakamichi, Noritaka

AU - Kawagoe, Hirofumi

AU - Ogura, Masato

AU - Fukumori, Ryo

AU - Nakazato, Ryota

AU - Fujikawa, Koichi

AU - Kou, Miki

AU - Yoneda, Yukio

PY - 2012/11

Y1 - 2012/11

N2 - The underlying mechanisms are still unclear for the neuroprotective properties of nicotine to date, whereas we have shown functional expression of nicotinic acetylcholine receptors (nAChRs) responsible for the influx of extracellular Ca2+ in cultured rat cortical astrocytes. In this study, we investigated the possible involvement of astrocytic nAChRs in the neuroprotection by this agonist. Exposure to nicotine predominantly induced mRNA expression of glial cell line-derived neurotrophic factor (GDNF) among the different neurotrophic factors examined in cultured astrocytes, in a manner sensitive to nAChR antagonists, nifedipine, and aCa2+ chelator. Nicotine significantly increased GDNF in a concentration-dependent manner in cultured astrocytes but not in neurons or neural progenitors even at the highest concentration used. In cultured astrocytes, a transient increase was seen in the expression of mRNA and corresponding protein for GDNF during sustained exposure to nicotine for 24 hr. Cytotoxicity mediated by oxidative, calcium, mitochondrial, or endoplasmic reticulum stress was invariably protected against in cortical neurons cultured with conditioned medium from astrocytes previously exposed to nicotine, and preincubation with the anti-GDNF antibody reduced the neuroprotection by conditioned medium from astrocytes exposed to nicotine. Intraperitoneal administration of nicotine transiently increased the number of cells immunoreactive for both GDNF and glial fibrillary acidic protein in rat cerebral cortex. These results suggest that astrocytic nAChRs play a role in the neuroprotection against different cytotoxins after predominant upregulation of GDNF expression through a mechanism relevant to the acceleration of extracellular Ca2+ influx in rat brain in a particular situation.

AB - The underlying mechanisms are still unclear for the neuroprotective properties of nicotine to date, whereas we have shown functional expression of nicotinic acetylcholine receptors (nAChRs) responsible for the influx of extracellular Ca2+ in cultured rat cortical astrocytes. In this study, we investigated the possible involvement of astrocytic nAChRs in the neuroprotection by this agonist. Exposure to nicotine predominantly induced mRNA expression of glial cell line-derived neurotrophic factor (GDNF) among the different neurotrophic factors examined in cultured astrocytes, in a manner sensitive to nAChR antagonists, nifedipine, and aCa2+ chelator. Nicotine significantly increased GDNF in a concentration-dependent manner in cultured astrocytes but not in neurons or neural progenitors even at the highest concentration used. In cultured astrocytes, a transient increase was seen in the expression of mRNA and corresponding protein for GDNF during sustained exposure to nicotine for 24 hr. Cytotoxicity mediated by oxidative, calcium, mitochondrial, or endoplasmic reticulum stress was invariably protected against in cortical neurons cultured with conditioned medium from astrocytes previously exposed to nicotine, and preincubation with the anti-GDNF antibody reduced the neuroprotection by conditioned medium from astrocytes exposed to nicotine. Intraperitoneal administration of nicotine transiently increased the number of cells immunoreactive for both GDNF and glial fibrillary acidic protein in rat cerebral cortex. These results suggest that astrocytic nAChRs play a role in the neuroprotection against different cytotoxins after predominant upregulation of GDNF expression through a mechanism relevant to the acceleration of extracellular Ca2+ influx in rat brain in a particular situation.

KW - Astrocytes

KW - GDNF

KW - NAChR

KW - Neuroprotection

KW - Nicotine

UR - http://www.scopus.com/inward/record.url?scp=84866051868&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866051868&partnerID=8YFLogxK

U2 - 10.1002/jnr.23101

DO - 10.1002/jnr.23101

M3 - Article

C2 - 22807215

AN - SCOPUS:84866051868

VL - 90

SP - 2074

EP - 2085

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 11

ER -