Chronic nicotine exposure inhibits estrogen-mediated synaptic functions in hippocampus of female rats

Raval, Ami P.; Sick, Justin; Gonzalez, Gabriel J.; DeFazio, R. Anthony; Dong, Chuanhui; Sick, Thomas J.

doi:10.1016/j.neulet.2012.04.015

Cited by 12 publications

(9 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, ER-positive tumor tissues had preferentially higher α9-nAChR mRNA expression in comparison to ER-negative tumor tissues. Chronic nicotine treatment reduced the ERβ protein expression in brain hippocampus and cortical cells in female rats (d'Adesky et al, 2018;Raval et al, 2012). Further, intact ovaries or E2 supplementation increases the nicotine intake, thus promoting the rewarding effects of nicotine in female rats (Flores, Pipkin, Uribe, Perez, & O'Dell, 2016).…”

Section: Discussionmentioning

confidence: 93%

Structural binding perspectives of a major tobacco alkaloid, nicotine, and its metabolite cotinine with sex‐steroid nuclear receptors

Rehan

Ahmad²,

Beg

2020

J of Applied Toxicology

View full text Add to dashboard Cite

Globally, more than a billion people smoke tobacco making it one of the biggest public health problems and a leading risk factor for global deaths. Nicotine, the main alkaloid in tobacco, has been shown to be associated with fertility problems in men and women. The adverse effects of tobacco/nicotine on reproduction have been attributed to deleterious effects on gametes, steroidogenic imbalance, and competitive inhibition of steroid receptors. The present study reports the sex‐steroid receptor disrupting potential of nicotine and its major metabolite cotinine against the estrogen receptor‐α (ERα), ERβ, androgen receptor (AR), and progesterone receptor (PR). Both ligands bound in the ligand‐binding pockets of ERα, ERβ, AR and PR and formed important hydrophobic interactions with different amino‐acid residues of receptors. Most of the residues of ERα, ERβ, AR and PR interacting with nicotine and cotinine were common with those of native/bound ligands of the receptors. Interacting amino acids most important for binding of nicotine and cotinine with each receptor were identified by loss in accessible surface area. Amino acids Leucine‐346, Leucine‐384 and Phenylalanine‐404 for ERα; Methionine‐336, Phenylalanine‐356 and Leucine‐298 for ERβ; and Leucine‐704 and Leucine‐718, respectively for AR and PR, were the most important residues for binding with nicotine and cotinine. Among the four receptors, based on the number of interactions, nicotine and cotinine had greater potential to interfere in the signaling of ERβ. In conclusion, the results suggested that nicotine and cotinine bind and interact with sex‐steroid nuclear receptors and have potential to interfere in the steroid hormone signaling resulting in reproductive dysfunction.

show abstract

Section: Discussionmentioning

confidence: 93%

Structural binding perspectives of a major tobacco alkaloid, nicotine, and its metabolite cotinine with sex‐steroid nuclear receptors

Rehan

Ahmad²,

Beg

2020

J of Applied Toxicology

View full text Add to dashboard Cite

show abstract

“…Conversely, periodic activation of ER-β significantly decreased inflammasome activation and reduced post-ischemic neuronal death in the hippocampus of reproductively senescent female rats. It has been shown that aging as well as long-term nicotine usage reduces ER-β availability in the brain [ 30 , 31 ]. Therefore, nicotine-induced inflammasome activation in the brain could be due to the direct immunomodulatory nature of nicotine or the loss of ER-β following long-term nicotine exposure in the brain.…”

Section: Discussionmentioning

confidence: 99%

“…To obtain sustained nicotine delivery, osmotic pumps (type 2ML2, Alzet Corp., Palo Alto, CA, USA) containing nicotine or saline were implanted in rats for 16–21 days as described [ 30 ]. The pump delivered a fixed and continuous dose of nicotine hydrogen tartrate (4.5 mg/kg/day, equivalent to 1.5 mg/kg/day free base) throughout the 16–21 days.…”

Section: Methodsmentioning

confidence: 99%

Nicotine Alters Estrogen Receptor-Beta-Regulated Inflammasome Activity and Exacerbates Ischemic Brain Damage in Female Rats

d’Adesky

Vaccari

Bhattacharya

et al. 2018

IJMS

View full text Add to dashboard Cite

Smoking is a preventable risk factor for stroke and smoking-derived nicotine exacerbates post-ischemic damage via inhibition of estrogen receptor beta (ER-β) signaling in the brain of female rats. ER-β regulates inflammasome activation in the brain. Therefore, we hypothesized that chronic nicotine exposure activates the inflammasome in the brain, thus exacerbating ischemic brain damage in female rats. To test this hypothesis, adult female Sprague-Dawley rats (6–7 months old) were exposed to nicotine (4.5 mg/kg/day) or saline for 16 days. Subsequently, brain tissue was collected for immunoblot analysis. In addition, another set of rats underwent transient middle cerebral artery occlusion (tMCAO; 90 min) with or without nicotine exposure. One month after tMCAO, histopathological analysis revealed a significant increase in infarct volume in the nicotine-treated group (64.24 ± 7.3 mm3; mean ± SEM; n = 6) compared to the saline-treated group (37.12 ± 7.37 mm3; n = 7, p < 0.05). Immunoblot analysis indicated that nicotine increased cortical protein levels of caspase-1, apoptosis-associated speck-like protein containing a CARD (ASC) and pro-inflammatory cytokines interleukin (IL)-1β by 88% (p < 0.05), 48% (p < 0.05) and 149% (p < 0.05), respectively, when compared to the saline-treated group. Next, using an in vitro model of ischemia in organotypic slice cultures, we tested the hypothesis that inhibition of nicotine-induced inflammasome activation improves post-ischemic neuronal survival. Accordingly, slices were exposed to nicotine (100 ng/mL; 14–16 days) or saline, followed by treatment with the inflammasome inhibitor isoliquiritigenin (ILG; 24 h) prior to oxygen-glucose deprivation (OGD; 45 min). Quantification of neuronal death demonstrated that inflammasome inhibition significantly decreased nicotine-induced ischemic neuronal death. Overall, this study shows that chronic nicotine exposure exacerbates ischemic brain damage via activation of the inflammasome in the brain of female rats.

show abstract

“…There is widespread agreement that NR2B function increases in hippocampal CA1 pyramidal neurons after E2 treatment, but the mechanism is controversial, with reports of increased NR2B mRNA, protein, and protein phosphorylation (Xu et al, 2011;Nebieridze et al, 2012;Raval et al, 2012) in vivo, decreased NR2B phosphorylation in response to E2 using cultured cortical neurons (Liu et al, 2012), or enhanced recruitment of NR2B receptors to synapses but no change in protein or phosphorylation levels (Snyder et al, 2011). E2 treatment is known to increase extracellular signal-regulated kinase phosphorylation in hippocampus in an NMDA-dependent manner .…”

Section: Discussionmentioning

confidence: 99%

Analysis of Kalirin-7 Knockout Mice Reveals Different Effects in Female Mice

et al. 2012

View full text Add to dashboard Cite

Estradiol treatment of ovariectomized rodents is known to affect the morphology of dendritic spines and produce behavioral and cognitive effects. Kalirin-7 (Kal7), a postsynaptic density (PSD)-localized Rho-guanine nucleotide exchange factor, is important for dendritic spine formation and stability. Male Kal7 knockout [Kal7(KO)] mice exhibit a number of abnormal behavioral and biochemical phenotypes. Given that chronic 17␤-estradiol (E2) replacement of ovariectomized rats enhanced Kal7 expression in the hippocampus and primary hippocampal cultures, we assessed the behavioral and biochemical effects of chronic E2 treatment of ovariectomized female wild-type and Kal7(KO) mice. Both intact and ovariectomized Kal7(KO) female mice exhibited decreased anxiety-like behavior compared with the corresponding wild type in the elevated zero maze and were unaffected by E2 treatment. Chronic E2 decreased locomotor activity in the open field and enhanced performance in a passive-avoidance fear conditioning task, which were both unaffected by genotype. Kal7(KO) female mice engaged in significantly more object exploration, both familiar and novel, than did wild-type females. E2 enhanced the acute locomotor response to cocaine, with no significant effect of genotype. Similar to Kal7(KO) males, Kal7(KO) females had decreased levels of Nmethyl-D-aspartate receptor 2B in hippocampal PSD fractions with no effect of E2 treatment. The differing behavioral effects of Kal7 ablation in female and male mice may offer insight into the molecular underpinnings of these differences.

show abstract

Chronic nicotine exposure inhibits estrogen-mediated synaptic functions in hippocampus of female rats

Cited by 12 publications

References 32 publications

Structural binding perspectives of a major tobacco alkaloid, nicotine, and its metabolite cotinine with sex‐steroid nuclear receptors

Structural binding perspectives of a major tobacco alkaloid, nicotine, and its metabolite cotinine with sex‐steroid nuclear receptors

Nicotine Alters Estrogen Receptor-Beta-Regulated Inflammasome Activity and Exacerbates Ischemic Brain Damage in Female Rats

Analysis of Kalirin-7 Knockout Mice Reveals Different Effects in Female Mice

Contact Info

Product

Resources

About