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Neuroscience Bulletin 2022年第7期38卷 703-719页

作者： Yunyun Zhang Huiming Li Xinxin Zhang Sa Wang Dan Wang Jiajia Wang Tingting Tong Zhen Zhang Qianzi Yang Hailong Dong Department of Anesthesiology and Perioperative Medicine Xijing HospitalThe Fourth Military Medical UniversityXi'an 710032China

A growing number of studies have identified sex differences in response to general anesthesia;however,the underlying neural mechanisms are unclear.The medial preoptic area(MPA),an important sexually dimorphic structure and a critical hub for regulating consciousness transition,is enriched with estrogen receptor alpha(ERa),particularly in neuronal clusters that participate in regulating sleep.We found that male mice were more sensitive to sevoflurane.Pharmacological inhibition of ERαin the MPA abolished the sex differences in sevoflurane anesthesia,in particular by extending the induction time and facilitating emergence in males but not in females.Suppression of ERαin vitro inhibited GABAergic and glutamatergic neurons of the MPA in males but not in females.Furthermore,ERα.knockdown in GABAergic neurons of the male MPA was sufficient to eliminate sex differences during sevoflurane anesthesia.Collectively,MPA ERαpositively regulates the activity of MPA GABAergic neurons in males but not in females,which contributes to the sexdifference of mice in sevoflurane anesthesia.

关键词： sex difference Anesthesia Estrogen receptor alpha Medial preoptic area Sevoflurane

sex difference in the Repolarization Currents of Rabbit Ventricular Cells

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2005年第3期25卷 260-262页

作者：阮燕菲刘念周强李泱王琳 Department of Cardiology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

The current difference between male and female rabbit ventricular myocytes was investigated for elucidating the mechanism of longer QT interval and higher incidence of drug-associated torsade de pointes in female rabbits than in male rabbits. Whole cell patch clamp technique was used to record APD, I_to, I_K,tail, I_K1 and I_Ca,L of myocytes from left ventricular apex. There was no difference in the membrane capacitance between male and female rabbit myocytes. APD_90 was longer in female rabbits (560.4±26.5 ms, n=15) than in male ones (489.0±20.7 ms, n=14), Pdifference in I_to, I_K1 and I_Ca,L between male rabbits and female rabbits (P>0.05). The lower I_K,tail of female rabbit myocytes may contribute to the longer repolarization and the higher incidence of drug-associated torsade de pointes.

关键词： patch clamp technique ventricular myocytes potassium current calcium current sex difference

sex difference of Stereopsis in Chinese Rural Children and Adolescents

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Sex Difference of Stereopsis in Chinese Rural Children and A...

sex differences in Neuropathology and Cognitive Behavior in APP/PS1/tau Triple-Transgenic Mouse Model of Alzheimer's Disease

第二十一届全国心理学学术会议

作者： Yu’e Yao Jingjing Zhao School of Psychology Shaanxi Normal University and Shaanxi Key Laboratory of Behavior and Cognitive Neuroscience

Background: Eighty percent of the information in daily activities, such as driving, playing balls and watching 3D movies relies on stereopsis(binocular depth perception). Stereopsis is an advanced visual function based on binocular disparity. It is generally believed that stereopsis matured at 7-9 years old. However, empirical studies of stereopsis are relatively few. The current research first performed literature review of the stereopsis research. A meta-analysis was then conducted in clinical populations. We finally analyzed the stereopsis ability in a group of Chinese rural children and adolescents and examined sex difference of stereopsis in the population. Study 1: Literature review revealed that there were stereopsis deficits in patients with schizophrenia, autism, Parkinson’s disease, Alzheimer’s disease, depression and anxiety. Seven studies with means and standard deviations about stereopsis ability in clinical populations were included in the meta-analysis. Meta-analysis demonstrates that patients with schizophrenia had a marked deficit in stereopsis compared with the control group(Cohen’s d=0.643, psex difference was found in stereopsis: girls showed better stereopsis ability than boys(log transformed stereopsis: girls 1.66+0.16, boys 1.79+0.31, F(1,219)) =12.57, p<0.001, η=0.055;arc transformed accuracy of stereoscopic vision test: girls 1.41+0.30, boys 1.22+0.46, F(1,219)) =13.48, p<0.001, η=0.058). Conclusion: The stereopsis deficit exists in various diseases, including schizophrenia, autism, Parkinson’s disease, Alzheimer’s disease, depression and anxiety. Stereopsis develops

关键词： binocular depth perception stereopsis stereo acuity meta-analysis sex difference

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Neuroscience Bulletin 2018年第5期34卷 736-746页

作者： Jun-Ting Yang Zhao-Jun Wang Hong-Yan Cai Li Yuan Meng-Ming Hu Mei-Na Wu Jin-Shun Qi Department of Physiology Shanxi Medical University Department of Microbiology and Immunology Shanxi Medical University Department of Physiology Changzhi Medical College

Alzheimer＇s disease （AD） is the most common form of dementia among the elderly, characterized by amyloid plaques, neurofibrillary tangles, and neuroinflam- mation in the brain, as well as impaired cognitive behaviors. A sex difference in the prevalence of AD has been noted, while sex differences in the cerebral pathology and relevant molecular mechanisms are not well clarified. In the present study, we systematically investigated the sex differences in pathological characteristics and cognitive behavior in 12-month-old male and female APP/PSI/tau triple-trans- genic AD mice （3xTg-AD mice） and examined the molecular mechanisms. We found that female 3×Tg-AD mice displayed more prominent amyloid plaques, neurofib- rillary tangles, neuroinflammation, and spatial cognitive deficits than male 3×Tg-AD mice. Furthermore, the expres- sion levels of hippocampal protein kinase A-cAMP response element-binding protein （PKA-CREB） and p38- mitogen-activated protein kinases （MAPK） also showed sex difference in the AD mice, with a significant increase in the levels of p-PKA/p-CREB and a decrease in the p-p38 in female, but not male, 3×Tg-AD mice. We suggest that an estrogen deficiency-induced PKA-CREB-MAPK signaling disorder in 12-month-old female 3×Tg-AD mice might be involved in the serious pathological and cognitive damage in these mice. Therefore, sex differences should be taken into account in investigating AD biomarkers and related target molecules, and estrogen supplementation or PKA-CREB- MAPK stabilization could be beneficial in relieving the pathological damage in AD and improving the cognitive behavior of reproductively-senescent females.

关键词： sex difference 3xTg-AD mouse Amyloid plaque Neurofibrillary tangle Neuroinflammation Spatial memory

Mediation Effects of Placental Inflammatory Transcriptional Biomarkers on the sex-Dependent Associations between Maternal Phthalate Exposure and Infant Allergic Rhinitis: A Population-Based Cohort Study

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Biomedical and Environmental Sciences 2022年第8期35卷 711-721页

作者： WANG Jian Qing LI Zhi Juan GAO Hui SHENG Jie LIANG Chun Mei HU Ya Bin XIA Xun HUANG Kun WANG Su Fang ZHU Peng HAO Jia Hu TAO Fang Biao Department of Maiernal Child and Adolescent HealthSchool of Public HealthAnhui Medical UniversityHefei 230032AnhuiChina MOE Key Laboratory of Popularion Health across Life Cycle Hefei 230032AnhuiChina NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract Hefei 230032AnhuiChina Anhui Provincial Key Laboratory of Population Health and Aristogenics Anhui Medical UniversityHefei 230032AnhuiChina The Fourth Affiliated Hospital Anhui Medical UniversiyHefei 230022AnhuiChina Department of Pediatrics First Afiliated Hospital of Anhui Medical UniversityHefei 230022AnhuiChina

Objective Prenatal phthalate exposure has been associated with placental inflammatory factors and infant allergic rhinitis(AR).However,the results are inconclusive.We designed a population-based cohort study to examine the effects of placental inflammatory biomarkers on the sex-dependent associations between maternal phthalate exposure and infant AR.Methods A total of 2,348 pregnant women from Ma’anshan,Anhui Province,China,who were screened before antenatal visits and met the inclusion criteria,were included in the present study.We assessed AR in their offspring aged 36 months with a questionnaire.Quantitative PCR was performed to measure placental inflammatory factor m RNAs.The independent samples t-test and multivariable logistic regression were used to determine the associations between infant AR and maternal phthalates.Results Childhood AR may be related to education and family monthly income(P = 0.01).The phthalate metabolites,mono(2-ethylhexyl) phthalate(MEHP),mono(2-ethyl-5-hydroxyl) phthalate(MEHHP),in pregnant women were associated with a significantly increased risk for infant AR in males[P < 0.05;odds ratio(OR):1.285;95% confidence interval(CI):1.037-1.591,and OR:1.232,95% CI:1.008-1.507,respectively],but not females.Additionally,irritably-increased expression levels of HO-1 and IL-4 were associated with AR in male infants(OR:1.175;95% CI:1.038-1.329 and OR:1.181;95% CI:1.056-1.322,respectively).The association between maternal urinary MEHHP and placental HO-1 was marginally significant according to mediation analysis.Conclusion The associations of maternal MEHHP and MEOHP levels with fetal AR in males were significant.Placental HO-1 was a fractional mediator in the associations between MEHHP and AR.Thus,the placenta should be further investigated as a potential mediator of maternal exposure-induced disease risk in children.

关键词： Phthalate Infants Allergic rhinitis Inflammation sex difference

Influence of biological sex and exercise on murine cardiac metabolism

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Journal of Sport and Health Science 2022年第4期11卷 479-494页

作者： Kyle Fulghum Helen E.Collins Steven P.Jones Bradford G.Hill Diabetes and Obesity Center Department of MedicineDivision of Environmental MedicineChristina Lee Brown Envirome InstituteUniversity of LouisvilleLouisvilleKY 40202USA Department of Physiology University of LouisvilleLouisvilleKY 40202USA

Although the structural and functional effects of exercise on the heart are well established,the metabolic changes that occur in the heart during and after exercise remain unclear.In this study,we used metabolomics to assess time-dependent changes in the murine cardiac metabolome following 1 session of treadmill exercise.After the exercise bout,we also recorded blood lactate,glucose,and ketone body levels and measured cardiac mitochondrial respiration.In both male and female mice,moderate-and high-intensity exercise acutely increased blood lactate levels.In both sexes,low-and moderate-intensity exercise augmented circulating 3-hydroxybutryrate levels immediately after the exercise bout;however,only in female mice did high-intensity exercise increase 3-hydroxybutyrate levels,with significant increases occurring 1 h after the exercise session.Untargeted metabolomics analyses of sedentary female and male hearts suggest considerable sex-dependent differences in basal cardiac metabolite levels,with female hearts characterized by higher levels of pantothenate,pyridoxamine,homoarginine,tryptophan,and several glycerophospholipid and sphingomyelin species and lower levels of numerous metabolites,including acetyl coenzyme A,glucuronate,gulonate,hydroxyproline,prolyl-hydroxyproline,carnosine,anserine,and carnitinylated and glycinated species,as compared with male hearts.Immediately after a bout of treadmill exercise,both male and female hearts had higher levels of corticosterone;however,female mice showed more extensive exercise-induced changes in the cardiac metabolome,characterized by significant,time-dependent changes in amino acids(e.g.,serine,alanine,tyrosine,tryptophan,branched-chain amino acids)and the ketone body 3-hydroxybutyrate.Results from experiments using isolated cardiac mitochondria suggest that high-intensity treadmill exercise does not acutely affect respiration or mitochondrial coupling;however,female cardiac mitochondria demonstrate generally higher adenosine diphosphate sensitivity compared with male ca

关键词： Ketone bodies Metabolomics Mitochondria Physical activity sex difference

Age-specific mortality and fecundity of a spider mite under diet restriction and delayed mating

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Insect Science 2022年第3期29卷 889-899页

作者： Guang-Yun Li Zhi-Qiang Zhang Centre for Biodiversity and Biosecurity School of Biological SciencesUniversity of AucklandAucklandNew Zealand Manaaki Whenua-Landcare Research AucklandNew Zealand Key Laboratory of Entomology and Pest Control Engineering College of Plant ProtectionSouthwest UniversityChongqingChina

Numerous experimental life-history studies on aging are mainly baised on two classical models—fruit fly Drosophila melanogaster(Meigen)and nematode Caenorhab-ditis elegans(Maupas)—with relatively little attention given to other organisms with different life-history characters.Two-spotted spider mite Tetranychus urticae Koch(Acari:Tetranychidae)differs from many other arthropods in that the females continue their growth in the early adult stage and can reproduce sexually and asexually.In this study,the influences of dietary restriction and delayed mating on the aging patterns of the spider mite were examined with the prevailing survival and reproduction trade-off hypothesis of aging being tested.Significant sex-specific responses of the spider mites were found.The females showed longevity extension on diet restriction(fasting for 2 days in every 4 days)compared with their counterparts being fed ad libitum,and after delayed mating for 9 days,while the males displayed a decrease in lifespan when experiencing diet restriction but were not significantly influenced by delayed mating.Path analysis was used to investigate the relationship between mite survival and reproduction traits,including longevity,female lifetime reproduction,age at first reproduction,early reproductive efforts and late reproductive efforts,yielding no evidence for trade-offs between these life-history traits.The additive effects of dietary restriction and delayed mating in lifespan extension of female spider mites were confirmed,proving that diet restriction is a robust anti-aging intervention,and that later onset of reproduction can prolong adult lifespan in females.

关键词： age-specific mortality delayed mating diet restriction reproduction sex difference trade-off

Gender Role,But Not sex,Shapes Humans’Susceptibility to Emotion

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Neuroscience Bulletin 2021年第2期37卷 201-216页

作者： Jiajin Yuan Hong Li Quanshan Long Jiemin Yang Tatia M.C.Lee Dandan Zhang The Laboratory for Affect Cognition and Regulation Institute of Brain and Psychological SciencesSichuan Normal UniversityChengdu 610068China College of Psychology Shenzhen UniversityShenzhen 518060China Faculty of Psychology Southwest UniversityChongqing 400715China Department of Psychology The University of Hong KongHong Kong 999077China Shenzhen-Hong Kong Institute of Brain Science Shenzhen 518060China Shenzhen Institute of Neuroscience Shenzhen 518060China

It is unknown whether the famous sex-related difference in emotion processing is accounted for by biological sex,gender role,or their interaction.To clarify the issue,in Study 1 we recorded event-related potentials in response to negative and positive images of diverse intensities when 47 masculine(26 males)and 47 feminine(22 males)subjects performed a non-emotional task.The occipital P1 and N1 amplitudes were larger in women than in men,while feminine subjects showed larger N1 amplitudes than masculine subjects,regardless of sex.Moreover,feminine subjects showed enhanced frontocentral N2(210–270 ms)amplitudes for highly and mildly negative than for neutral stimuli,while masculine subjects showed an emotion effect only for highly negative stimuli.The feminine-specific effect for mildly negative stimuli was positively correlated to the feminine score,and this correlation was located to the anterior cingulate and the superior and medial frontal gyri.Furthermore,feminine but not masculine subjects showed enhanced parietal P3(330–560 ms)amplitudes for highly and mildly positive than for neutral stimuli,an effect positively related to the feminine score and localized to the precuneus,posterior cingulate,and superior temporal gyrus.Machine learning analyses verified that single-trial N2 and P3 amplitudes of feminine subjects reliably discriminated the intensity of negative and positive stimuli,respectively.For ecological considerations,in Study 2 we used an observational approach(n=300)and confirmed that feminine gender role,rather than biological sex,predicted individual differences in daily experience of emotion-related psychopathological symptoms.These findings provide solid evidence for the critical impact of gender role rather than sex on emotional susceptibility.

关键词： sex difference Gender role Emotional susceptibility Event-related potential Machine learning

sex-Dependent Glial Signaling in Pathological Pain:Distinct Roles of Spinal Microglia and Astrocytes

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Neuroscience Bulletin 2018年第1期34卷 98-108页

作者： Gang Chen Xin Luo M.Yawar Qadri Temugin Berta Ru-Rong Ji Department of Anesthesiology Duke University Medical Center Key Laboratory of Neuroregeneration of Jiangsu and the Ministry of Education Co-Innovation Center of Neuroregeneration Nantong University Pain Research Center Department of AnesthesiologyUniversity of Cincinnati Medical Center Department of Neurobiology Duke University Medical Center

Increasing evidence suggests that spinal micro- glia regulate pathological pain in males. In this study, we investigated the effects of several microglial and astroglial modulators on inflammatory and neuropathic pain follow- ing intrathecal injection in male and female mice. These modulators were the microglial inhibitors minocycline and ZVEID （a caspase-6 inhibitor） and the astroglial inhibitors L-α-aminoadipate （L-AA, an astroglial toxin） and car- benoxolone （a connexin 43 inhibitor）, as well as U0126 （an ERK kinase inhibitor） and D-JNKI-1 （a c-Jun N-terminal kinase inhibitor）. We found that spinal administration of minocycline or ZVEID, or Caspase6 deletion, reduced formalin-induced inflammatory and nerve injury-induced neuropathic pain primarily in male mice. In contrast, intrathecal L-AA reduced neuropathic pain but not inflam- matory pain in both sexes. Intrathecal U0126 and D-JNKI- 1 reduced neuropathic pain in both sexes. Nerve injury caused spinal upregulation of the astroglial markers GFAP and Connexin 43 in both sexes. Collectively, our data confirmed male-dominant microglial signaling but also revealed sex-independent astroglial signaling in the spinal cord in inflammatory and neuropathic pain.

关键词： Astrocytes - Microglia sex difference Spinal cord

sex-specific effects of Eugenia punicifolia extract on gastric ulcer healing in rats

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World Journal of Gastroenterology 2018年第38期24卷 4369-4383页

作者： Larissa Lucena Périco Vinícius Peixoto Rodrigues Rie Ohara Gabriela Bueno Vania Vasti Alfieri Nunes Raquel Cássia dos Santos Ana Carolina Lima Camargo Luis Antuio Justulin Joior Sérgio Faloni de Andrade Viviane Miranda Bispo Steimbach Luísa Mota da Silva Lúcia Regina Machado da Rocha Wagner Vilegas Catarina dos Santos Clélia Akiko Hiruma-Lima Department of Physiology Institute of BiosciencesSa Paulo State University(UNESP)Botucatu 18618-970Sa PauloBrazil Laboratory of Bioactive Compounds Sao Francisco UniversityBraganca Paulista 12916-900Sa PauloBrazil Department of Morphology Institute of BiosciencesSao Paulo State University(UNESP)Botucatu 18618-970Sao PauloBrazil Programa de Po-graduacao em Ciecias Farmaco-ticas Nuleo de Investigacoes Quiico-Farmaceticas(NIQFAR)Universidade do Vale do Itajai-UNIVALIItajai 88302-901Santa CatarinaBrazil Coastal Campus of Sa Vicente Sa Paulo State University(UNESP)Sa Vicente 11330-900Sa PauloBrazil Department of Biological Science Faculty of Sciences and LanguagesSa Paulo State University(UNESP)Assis 19806-900SaPauloBrazil

AIM To evaluate the sex-specific effects of a hydroalcoholic extract from Eugenia punicifolia(HEEP) leaves on gastric ulcer healing.METHODS In this rat study involving males, intact(cycling) females, and ovariectomized females, gastric ulcers were induced using acetic acid. A vehicle, lansoprazole, or HEEP was administered for 14 d after ulcer induction. Body weight was monitored throughout the treatment period. At the end of treatment, the rats were euthanized and the following in vivo and in vitro investigations were performed: macroscopic examination of the lesion area and organ weights, biochemical analysis, zymography, and evaluation of protein expression levels. Additionally, the concentration-dependent effect of HEEP was evaluated in terms of subacute toxicity and cytotoxicity.RESULTS Compared to the vehicle, HEEP demonstrated a great healing capacity by substantially reducing the ulcerative lesion area in males(52.44%), intact females(85.22%), and ovariectomized females(65.47%), confirming that HEEP accelerates the healing of acetic acidinduced gastric lesions and suggesting that this effect is modulated by female sex hormones. The antiulcer effect of HEEP was mediated by prostaglandin E2 only in male rats. Overall, the beneficial effect of HEEP was the highest in intact females. Notably, HEEP promoted the expression of vascular endothelial growth factor(intact vs ovariectomized females) and decreased the expression of Caspase-8 and Bcl-2(intact female vs male or ovariectomized female). Additionally, HEEP enhanced fibroblast proliferation and migration into a wounded area in vitro, confirming its healing effect. Finally, no sign of subacute toxicity or cytotoxicity of HEEP was observed.CONCLUSION In gastric ulcers, HEEP-induced healing(modulated by female sex hormones; in males, mediated by prostaglandin) involves extracellular matrix remodeling, with gastric mucosa cell proliferation and migration.

关键词： Eugenia punicifolia Gastric ulcer healing Acetic acid sex difference Myrtaceae Toxicity