Abstract
Nicotine, the addictive agent in cigarettes, reduces circulating estradiol-17β (E 2) and inhibits E 2-mediated intracellular signaling in hippocampus of female rats. In hippocampus, E 2-signaling regulates synaptic plasticity by phosphorylation of the N-methyl-d-aspartic acid receptor subunit NR2B and cyclic-AMP response element binding protein (pCREB). Therefore, we hypothesized that chronic nicotine exposure induces synaptic dysfunction in hippocampus of female rats. Female rats were exposed to nicotine or saline for 16days followed by electrophysiological analysis of hippocampus. Briefly, population measurements of excitatory post-synaptic field potentials (fEPSPs) were recorded from stratum radiatum of the CA1 hippocampal slice subfield. A strict software-controlled protocol was used which recorded 30min of baseline data (stimulation rate of 1/min), a paired-pulse stimulation sequence followed by tetanic stimulation, and 1h of post-tetanus recording. EPSP amplitude and the initial EPSP slope were measured off-line. We then investigated by Western blot analysis the effects of nicotine on hippocampal estrogen receptor-beta (ER-β), NR2B and pCREB. The results demonstrated significantly decreased post-tetanic potentiation and paired-pulse facilitation at the 40, and 80ms interval in nicotine-exposed rats compared to the saline group. Western blot analysis revealed that nicotine decreased protein levels of ER-β, NR2B, and pCREB. We also confirmed the role of E 2 in regulating NR2B and pCREB phosphorylation by performing Western blots in hippocapmal tissue obtained from E 2-treated ovariectomized rats. In conclusion, chronic nicotine exposure attenuates short-term synaptic plasticity, and the observed synaptic defects might be a consequence of loss of estradiol-17β-signaling. However, determining the exact molecular mechanisms of chronic nicotine exposure on synaptic plasticity specific to the female brain require further investigation.
| Original language | English |
|---|---|
| Pages (from-to) | 41-46 |
| Number of pages | 6 |
| Journal | Neuroscience Letters |
| Volume | 517 |
| Issue number | 1 |
| DOIs | |
| State | Published - May 23 2012 |
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Keywords
- Cyclic-AMP response element binding
- Estrogen receptors
- Hippocampus
- Long-term potentiation
- Paired-pulse modulation
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Chronic nicotine exposure inhibits estrogen-mediated synaptic functions in hippocampus of female rats. / Raval, Ami; Sick, Justin T.; Gonzalez, Gabriel J.; DeFazio, R. Anthony; Dong, Chuanhui; Sick, Thomas.
In: Neuroscience Letters, Vol. 517, No. 1, 23.05.2012, p. 41-46.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Chronic nicotine exposure inhibits estrogen-mediated synaptic functions in hippocampus of female rats
AU - Raval, Ami
AU - Sick, Justin T.
AU - Gonzalez, Gabriel J.
AU - DeFazio, R. Anthony
AU - Dong, Chuanhui
AU - Sick, Thomas
PY - 2012/5/23
Y1 - 2012/5/23
N2 - Nicotine, the addictive agent in cigarettes, reduces circulating estradiol-17β (E 2) and inhibits E 2-mediated intracellular signaling in hippocampus of female rats. In hippocampus, E 2-signaling regulates synaptic plasticity by phosphorylation of the N-methyl-d-aspartic acid receptor subunit NR2B and cyclic-AMP response element binding protein (pCREB). Therefore, we hypothesized that chronic nicotine exposure induces synaptic dysfunction in hippocampus of female rats. Female rats were exposed to nicotine or saline for 16days followed by electrophysiological analysis of hippocampus. Briefly, population measurements of excitatory post-synaptic field potentials (fEPSPs) were recorded from stratum radiatum of the CA1 hippocampal slice subfield. A strict software-controlled protocol was used which recorded 30min of baseline data (stimulation rate of 1/min), a paired-pulse stimulation sequence followed by tetanic stimulation, and 1h of post-tetanus recording. EPSP amplitude and the initial EPSP slope were measured off-line. We then investigated by Western blot analysis the effects of nicotine on hippocampal estrogen receptor-beta (ER-β), NR2B and pCREB. The results demonstrated significantly decreased post-tetanic potentiation and paired-pulse facilitation at the 40, and 80ms interval in nicotine-exposed rats compared to the saline group. Western blot analysis revealed that nicotine decreased protein levels of ER-β, NR2B, and pCREB. We also confirmed the role of E 2 in regulating NR2B and pCREB phosphorylation by performing Western blots in hippocapmal tissue obtained from E 2-treated ovariectomized rats. In conclusion, chronic nicotine exposure attenuates short-term synaptic plasticity, and the observed synaptic defects might be a consequence of loss of estradiol-17β-signaling. However, determining the exact molecular mechanisms of chronic nicotine exposure on synaptic plasticity specific to the female brain require further investigation.
AB - Nicotine, the addictive agent in cigarettes, reduces circulating estradiol-17β (E 2) and inhibits E 2-mediated intracellular signaling in hippocampus of female rats. In hippocampus, E 2-signaling regulates synaptic plasticity by phosphorylation of the N-methyl-d-aspartic acid receptor subunit NR2B and cyclic-AMP response element binding protein (pCREB). Therefore, we hypothesized that chronic nicotine exposure induces synaptic dysfunction in hippocampus of female rats. Female rats were exposed to nicotine or saline for 16days followed by electrophysiological analysis of hippocampus. Briefly, population measurements of excitatory post-synaptic field potentials (fEPSPs) were recorded from stratum radiatum of the CA1 hippocampal slice subfield. A strict software-controlled protocol was used which recorded 30min of baseline data (stimulation rate of 1/min), a paired-pulse stimulation sequence followed by tetanic stimulation, and 1h of post-tetanus recording. EPSP amplitude and the initial EPSP slope were measured off-line. We then investigated by Western blot analysis the effects of nicotine on hippocampal estrogen receptor-beta (ER-β), NR2B and pCREB. The results demonstrated significantly decreased post-tetanic potentiation and paired-pulse facilitation at the 40, and 80ms interval in nicotine-exposed rats compared to the saline group. Western blot analysis revealed that nicotine decreased protein levels of ER-β, NR2B, and pCREB. We also confirmed the role of E 2 in regulating NR2B and pCREB phosphorylation by performing Western blots in hippocapmal tissue obtained from E 2-treated ovariectomized rats. In conclusion, chronic nicotine exposure attenuates short-term synaptic plasticity, and the observed synaptic defects might be a consequence of loss of estradiol-17β-signaling. However, determining the exact molecular mechanisms of chronic nicotine exposure on synaptic plasticity specific to the female brain require further investigation.
KW - Cyclic-AMP response element binding
KW - Estrogen receptors
KW - Hippocampus
KW - Long-term potentiation
KW - Paired-pulse modulation
UR - http://www.scopus.com/inward/record.url?scp=84861340552&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84861340552&partnerID=8YFLogxK
U2 - 10.1016/j.neulet.2012.04.015
DO - 10.1016/j.neulet.2012.04.015
M3 - Article
C2 - 22521583
AN - SCOPUS:84861340552
VL - 517
SP - 41
EP - 46
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 1
ER -