Mapping brain glutamate in humans: sex differences in cigarette smokers
绘制人类大脑谷氨酸图谱:吸烟者的性别差异
基本信息
- 批准号:10376214
- 负责人:
- 金额:$ 7.8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-04-01 至 2023-03-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAbstinenceAcetylcysteineAcuteAddressAdultAdvanced DevelopmentAffectAnatomyAnteriorAntismokingAttenuatedBehavioralBiological AssayBiological MarkersBrainBrain MappingBrain regionCigaretteCigarette SmokerCuesCysteineCytologyDataDevelopmentDiseaseDopamineDorsalEstrogensExcitatory Amino Acid AntagonistsFemaleFunctional Magnetic Resonance ImagingGlutamate TransporterGlutamatesGlutamineHealthHeart DiseasesHumanImaging TechniquesInsula of ReilLibidoLinkMagnetic Resonance SpectroscopyMaintenanceMalignant neoplasm of cervix uteriMeasurementMeasuresN-MethylaspartateNicotineNicotine WithdrawalNicotinic ReceptorsOvarian hormoneParticipantProgesteroneRadiation exposureResolutionRestRodentSamplingSatiationSelf AdministrationSerumSex DifferencesSignal TransductionSmokeSmokerSmokingSumTechniquesTestingThalamic structureTimeTissuesTobacco Use DisorderTreatment EfficacyVariantWithdrawal SymptomWomanaddictionantiportercigarette cravingcigarette smokingcingulate cortexdensityexperienceextracellularglutamatergic signalinghigh riskimprovedin vivomalemenneuropsychiatric disorderneurotransmissionnicotine replacementnicotine seeking behaviornon-smokernovelpersonalized medicinepreventable deathreduce symptomssegregationsexsmoking abstinencesmoking cessationsmoking interventionspecific biomarkersspectroscopic imagingtreatment responsevarenicline
项目摘要
PROJECT SUMMARY/ABSTRACT
Smoking is the leading cause of preventable death and disease in the U.S. Women are disproportionately
affected by smoking, as they not only have a higher risk of experiencing some health consequences of smoking,
such as heart disease, but also suffer sex-specific health issues, including cervical cancer. Women have more
difficulty maintaining long-term abstinence from smoking than men, possibly because they experience stronger
withdrawal symptoms and greater relief of these symptoms after resumption of smoking. Despite their enhanced
need for smoking-cessation therapies, current first-line treatments, such as nicotine replacement, are less
effective for women than men. The underlying differences in brain function that drive these sex differences
remain unknown, and understanding them can guide development of personalized smoking cessation therapies.
Glutamatergic neurotransmission is a promising new target for smoking cessation therapy, but sex
differences in glutamate levels across the brain, which can impact the efficacy of glutamatergic treatments, have
not been investigated in smokers. Our preliminary data using single-voxel magnetic resonance spectroscopy
(MRS), have revealed important sex differences in the relationships of glutamate in the dorsal anterior cingulate
cortex (dACC), a region highly implicated in Tobacco Use Disorder, with sex (males vs. females) and smoking
state (overnight abstinent vs. post-smoking) in smokers. Moreover, glutamate in the dACC is also associated
with circulating estrogen, and possibly progesterone, in women who smoke. However, important relationships
between glutamate in other brain regions and these factors are yet to be explored. Echo-planar spectroscopic
imaging (EPSI), a state-of-the-art technique, permits measurement of glutamate in ~80 percent of the whole
brain in vivo in humans. Given our preliminary results using single-voxel MRS, we now propose to test
replicability of our finding in the dACC and to examine potential extension to other brain regions heavily
implicated in the behavioral states of Tobacco Use Disorder - the anterior insula and thalamus. We will also
perform exploratory analyses of relationships of glutamate across the brain with sex, smoking state, and ovarian
hormones.
Otherwise healthy, adult daily smokers (30 men and 30 women) will serve as participants for this study. They
will be tested twice, after overnight (~12 h) abstinence from smoking and after smoking their first cigarette of the
day. We will combine EPSI with analysis of circulating ovarian hormones in serum to address two specific aims:
Aim 1. Determine relationships between brain glutamate, sex, and circulating ovarian hormones. Aim 2.
Determine sex differences in acute effects of smoking on brain glutamate. The findings from this study will
provide important empirical information regarding glutamate levels across the brain in smokers and help guide
development of personalized, sex-specific smoking cessation therapies.
项目总结/文摘
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Jeffry R Alger其他文献
Jeffry R Alger的其他文献
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{{ item.author }}
{{ truncateString('Jeffry R Alger', 18)}}的其他基金
Novel Algorithms for Reducing Radiation Dose of CT Perfusion
减少 CT 灌注辐射剂量的新算法
- 批准号:
10220967 - 财政年份:2017
- 资助金额:
$ 7.8万 - 项目类别:
Novel Algorithms for Reducing Radiation Dose of CT Perfusion
减少 CT 灌注辐射剂量的新算法
- 批准号:
10006737 - 财政年份:2017
- 资助金额:
$ 7.8万 - 项目类别:
RESEARCH ANIMAL MAGNETIC RESONANCE IMAGING INSTRUMENT
研究动物磁共振成像仪
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2864968 - 财政年份:1999
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PEDIATRIC LOW GRADE ASTROCYTOMA--TREATMENT GUIDANCE
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2461212 - 财政年份:1997
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