Sex Specific Differences in GABA and Glutamate Levels in Response to Cigarette Smoke<br>

Sex Specific Differences in GABA and Glutamate Levels in Response to Cigarette Smoke

Research Article

Open Access

Anita Mandal¹, Sudhish Mishra² and Prabir Mandal^1*

¹Edward Waters College, Department of Biology, 1658 Kings Road, Jacksonville, FL 32209, USA

²MSU College of Human Medicine and Van Andel Institute, Department of Translational Science and Molecular Medicine, 333 Bostwick Avenue NE, Grand Rapids, MI 49503, USA

^*Corresponding author:

Prabir K. Mandal
Department of Biology
Edward Waters College, Jacksonville
FL 32209, USA
Tel: 904-470-8091
Fax: 904-470- 8047
E-mail: prabir.mandal0807@ewc.edu

Received January 28, 2013; Published February 10, 2013

Citation: Mandal A, Mishra S, Mandal P (2013) Sex Specific Differences in GABA and Glutamate Levels in Response to Cigarette Smoke. 2:614 doi:10.4172/scientificreports.614

Copyright: Â© 2013 Mandal A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Cigarette smoking act differently in men and women. Nicotine is the main psychoactive substance of tobacco and affects several neurological pathways through nicotinic acetylcholine receptors (nAChRs). Addiction to nicotine is developed by dopaminergic system with the involvement of GABAergic and glutamatergic systems. In the present study we have measured the circulating GABA and glutamate in smokers and non-smokers men and compared them with women. Our results showed that GABA levels are significantly less in men than women with greater difference among smokers. No difference was found in glutamate levels in men and women.

Keywords

Nicotine; Nicotinic acetylcholine receptors; Gamma- Amino Butyric Acid (GABA); Glutamate

Introduction

Men and women behave differently in response to cigarette smoke. Women are quicker to develop nicotine tolerance than men [1] and have higher rate of relapse [2,3]. Nicotine, a major substance of smoke binds to nicotinic acetylcholine receptors (nAChRs); ligandgated cation channels [4] and modulates its activity. Nicotine also up-regulates nAChRs, which is more readily reflected in males than females [5].

Chronic smoking also alters circulating sex-hormones [6], which in turn mediates nAChRs activity. Progesterone has been shown to inhibit nAChRs activity [7] and estrogen but not testosterone can block antinociceptive effect of nicotine in female mice [8,9].

Although, dopaminergic system is involved in nicotine addiction, involvement of glutamatergic and GABAergic system is crucial for long term addiction [10]. GABA and glutamate are major inhibitory and excitatory neurotransmitters and are involved in many neurological pathways [11,12]. Nicotine modulates release of GABA and glutamate through nAChRs [13].

This study aims to measure gamma amino butyric acid (GABA) and glutamate in men and women chronic smokers of African American (AA) descent. GABA is known to control dopamine release through receptors present on dopamine releasing neurons while Glutamate, a neurotransmitter associated with memory in the brain, causes increase in alertness and pleasure through acetyl choline and dopamine, respectively [14].

Materials and Methods

Sample collection

Blood samples were collected in sterile condition from 58 African American men and women volunteers as per the institutional guidelines and grouped on the basis of smoking behaviour. Plasma were separated from these samples by centrifugation for 10 min and stored at -20Â°C in aliquots until further use. Enzyme Linked Immuno-Sorbant Assay (ELISA) kits were purchased from Alpco, Salem (NH).

Plasma concentrations of GABA and Glutamate

Plasma levels of GABA and Glutamate were measured by ELISA according to manufacturersâ€™ instructions. Plates were read in EPOCH Elisa reader from Biotek (Winooski, VT) following manufacturersâ€™ protocol and data were analyzed using GEN5 software.

Statistical analysis

All the results were compared using studentsâ€™ paired T-test. To determine whether significant difference in changes were present between groups, ANOVA was performed with a set to 0.05. All data are reported as mean Â± SE.

Results

Plasma level of GABA is significantly decreased in male smokers (81.2 Â± 2.4 ng/ml as against 122.2 Â± 2.8 ng/ml) but not in female smokers (129.4 Â± 4.0 ng/ml as against 136.5 Â± 2.0 ng/ml), while Glutamate levels are decreased significantly in both males (10.5 Â± 5.0 Î¼g/ml as against 19.4 Â± 2.9 Î¼g/ml) and females (13.7 Â± 3.3 Î¼g/ml as against 19.3 Â± 3.1 Î¼g/ ml) when compared to non-smoking volunteers of same sex (Figure 1).

When concentrations of thses neurotransmitters were compared between men and women, we found significantly lower levels of GABA in men than women. The difference is highly significant in smokers. No significant difference was found in the levels of glutamate between men and women.

Discussion

In the present study, we analyzed effect of gender and cigarette smoking on circulating GABA and glutamate in African-American smokers and non-smokers. Our results showed that GABA levels are significantly lower in men as compared to women irrespective of their smoking behavior. However, smoker men showed further decrease in GABA level but no significant changes were observed in smoker women when compared to non-smokers.

Our results correlated with the study by Esterlis et al. [15], who reported higher GABA_A-BZR availability in brain of women than men, regardless of smoking status but in complete contrast to study by Epperson et al. [16], where lower GABA levels are reported in female smokers but not in male smokers, when compared to corresponding non-smokers. This gender specific difference is more evident by the fact that during hippocampus development, switch from depolarizing to hyperpolarizing GABA_A receptor mediated response occur earlier in females than males [17].

In addition to transient increase in GABAergic transmission, nicotine also enhances glutamatergic transmission through nAChRs [18], that desensitize them and ultimately effect on dopaminergic neurons. We didnâ€™t observe any sex-specific difference in glutamate levels. This may be a reason for lack of literature for gender specific studies on glutamatergic system. In an unrelated study Yararbas et al. [19] reported that nicotine induces conditioned place preference (CPP) through glutamate receptors in male rats but not in female rats.

For our study we collected samples randomly and didnâ€™t account for menstrual phase of women subjects. Thus, the effects of hormonal changes of women were not considered in this study. With these results we conclude that GABAergic system differs significantly between men and women but that difference is not evident for glutamatergic system.

Acknowledgement

This study was supported by James & Esther King Biomedical Research Program of Florida Department of Health Grant HBC-01 to Drs. Prabir K. Mandal (PI), Sudhish Mishra (Co-PI) and Anita Mandal (Co-PI) of Biology Department, Edward Waters College. Authors are grateful to subjects volunteered for the study. The technical help from our students, faculty and staff are highly appreciated and hereby acknowledged.

References