Dear Editor,Major depressive disorder(MDD)is associated with a high rate of suicide attempts(SA).Previous reports have identified risk factors for SA in MDD patients,including sex and metabolic disorders[1].However,to...Dear Editor,Major depressive disorder(MDD)is associated with a high rate of suicide attempts(SA).Previous reports have identified risk factors for SA in MDD patients,including sex and metabolic disorders[1].However,to our knowledge,the impact of sex differences on the association between body mass index(BMI)status and SA in patients with MDD has not been investigated.Th is study aimed to investigate:1)the sex diff erence in the prevalence of recent SA in Chinese drug-naïve fi rst-episode(DNFE)MDD patients,and 2)the eff ect of sex diff erence on the relationship between higher BMI(overweight or obese)and recent SA.Patients were recruited from the First Clinical Medical College of Shanxi Medical University from January 2015 to December 2017.All patients met the inclusion and exclusion criteria described in previous studies[2].展开更多
The mu oil tree(Vernicia montana Lour.) is a dioecious species, but the genetic mechanisms underlying its phenotypic sexual dimorphism are unclear. In this study, we determined two pivotal phases of sex differentiatio...The mu oil tree(Vernicia montana Lour.) is a dioecious species, but the genetic mechanisms underlying its phenotypic sexual dimorphism are unclear. In this study, we determined two pivotal phases of sex differentiation of mu oil tree via morphological and histological analyses of unisexual flowers:(Ⅰ) differentiation of male or female primordia to produce staminate flowers(SFs) or transient hermaphrodite flowers(HFs),and(Ⅱ) complete abortion of stamens in transient HFs to generate pistillate flowers(PFs). A total of 1621 sex-biased genes were identified by comparative transcriptome analysis which exhibited elevated rates of protein evolution than unbiased genes. The female-biased genes were enriched in the production of defense compounds while male-biased genes were focused on the production of viable pollens. Transcriptomebased analysis revealed that the differentially expressed genes(DEGs) between PFs and SFs in phase Ⅰ involved in abscisic acid(ABA), auxin(AUX), cytokinin(CK), ethylene(ET), and gibberellin(GA) biosynthesis and signaling showed higher expression levels in males than in females in general, whereas the DEGs involved in jasmonic acid(JA) and salicylic acid(SA) pathways displayed opposite expression patterns. Moreover,differentially expressed endogenous ABA, AUX, GAs, JA, and SA exhibited consistent biased expression patterns with the DEGs by UPLC-MSbased analysis. Exogenous application of an anti-ethylene plant growth regulator could promote the development of stamens in PFs and generated HFs. Comparative transcriptomic and hormonal analyses of PFs and SFs in phase Ⅱ indicated an increase in ET concentration when abortion of stamens in PFs occurred. This study suggested that phytohormones play key roles in sex dimorphism and ET may determine the development of stamens in PFs of mu oil tree, which provides an insight into plant sex differentiation mechanisms.展开更多
We studied sexual dimorphism in body size and shape and female reproductive characteristics in the Hainan Water Skink(Tropidophorus hainanus)from Hainan,South China.In our sample the largest female and male were 61.1 ...We studied sexual dimorphism in body size and shape and female reproductive characteristics in the Hainan Water Skink(Tropidophorus hainanus)from Hainan,South China.In our sample the largest female and male were 61.1 and 55.2 mm snout-vent length(SVL),respectively.The mean SVL was larger in adult females(52.0 mm)than in adult males(48.3 mm).Juveniles were sexually dimorphic in head length but not in other examined morphological variables.Adult males were longer in head length and shorter in abdomen length and fore-limb length than adult females of the same SVL.Ontogenetic shifts in sexual dimorphism in body shape were evident,as revealed by the fact that morphological differences between the sexes were more pronounced in adults than in juveniles.Females produced a single litter of 3–6 offspring per season from early August to early September.Litter size,litter mass and offspring(neonate)mass were positively related to female SVL.Neonate mass was independent of relative fecundity.From the above findings we draw three main conclusions.First,females are the larger sex in T.hainanus,and sexual dimorphism in body shape is more pronounced in adults than in juveniles.Second,larger female T.hainanus produce more and larger offspring and thus heavier litters than smaller ones.Third,the offspring size-number trade-off does is not evident in T.hainanus.展开更多
The Japanese Genji firefly Nipponoluciola cruciata is famous for geographic variation in flash pattern. Such geographic variation has also been well studied in terms of ecology and molecular phylogeny. However, there ...The Japanese Genji firefly Nipponoluciola cruciata is famous for geographic variation in flash pattern. Such geographic variation has also been well studied in terms of ecology and molecular phylogeny. However, there are very few studies on geographic variation in morphology of this species. This study focused on morphological characteristics of males of this species in Yamanashi and Gunma Prefectures separated by the Kanto Mountains in central Japan. Previous studies have shown that this species in the two prefectures exhibits different genetic features as well as different flash patterns. This study aimed to explore morphological characteristics of males of this species and performed multivariate analysis using measurements previously published in the literature. As a result, allometric analysis between body length and elytra width suggested that this species exhibits different allometric patterns between the two prefectures. Moreover, cluster analysis of measurements of genitalia suggested that this species is completely separated into two different groups between the two prefectures. These results suggest the importance of further morphological studies to clarify the divergence of this species.展开更多
Fisher's theory predicts equal sex ratios at the end of parental care if the cost associated with raising offspring of each sex is equal.However,sex ratios have important evolutionary consequences and are often bi...Fisher's theory predicts equal sex ratios at the end of parental care if the cost associated with raising offspring of each sex is equal.However,sex ratios have important evolutionary consequences and are often biased for many factors.Reported sex ratios are often biased in raptors,which display various degrees of reversed sexual dimorphism,but there seems no consistent pattern in their offspring sex ratios.In this study,we investigated the offspring sex ratio of the Eurasian Kestrel(Falco tinnunculus) and tested whether the patterns of biased sex ratios were related to laying order,egg mass,hatching order,laying date or clutch size.The brood sex ratio of the Eurasian Kestrel(male) in eggs was 47.0%,not statistically biased from 0.5,but in fledglings it was 40.8%,significantly biased from 0.5(p = 0.029).At population level,both primary and secondary sex ratios did not depart from parity.We found that clutch size and egg mass affected the secondary brood sex ratio,i.e.,the larger the clutch size,the larger the number of males and eggs producing sons were heavier than eggs producing daughters.Laying date affected both the primary and secondary sex ratios,and laying earlier is associated with a greater proportion of males.展开更多
A series of new cognitions on the morphogenesis of maize ( Zea mays L.) embryo have been obtained with scanning electron microscopy and semi-thin section techniques. 1. The proembryo. The proembryo from zygotic cell d...A series of new cognitions on the morphogenesis of maize ( Zea mays L.) embryo have been obtained with scanning electron microscopy and semi-thin section techniques. 1. The proembryo. The proembryo from zygotic cell divisions may be divided into three parts: proper, hypoblast and suspensor. The suspensor is short and small, and only exists transiently. As to the hypoblast there is a growth belt, which promotes elongation of the hypoblast. Eventually the upper portion of the hypoblast contributes to the formation of the coleorhiza and the remainder dries up, sticking to the end of the coleorhiza. 2. The maize embryo possesses dorsiventrality and cotyledon dimorphism. During early proembryo stage, the dorsiventrality appears in the proper of the embryo. On the ventral side, the cells are small with dense cytoplasm and few vacuoles. On the dorsal side, the cells are larger with lower cytoplasmic density and have more vacuoles. During later proembryo stage, the proper develops into two parts: the ventrum and the dorsurn. The ventrum rises up from the center of the ventral side. The dorsurn is composed of the marginal area of the ventral side and the whole dorsal side of the proper. During young embryo development, the ventrum differentiates into the coleoptile, apical meristem, hypocotyl, radicle and the main part of the coleorhiza. What is more important, the emergence of coleoptile primordium and radicular initials occur at the axis of the proper, then the coleoptile primordium expands from its two ends toward left and right to form a ring, and the endogenous radicular initials expand in all directions to form a conical radicular tip. All these morphogenetic activities of the ventrum follow a bilateral symmetrical pattern. The dorsurn forms the scutellum. primordium. Then the scutellum primordium, expands rapidly toward the left, right, front and back, while thickening itself, so as to make all components originating from the ventrum become hidden in the longitudinal groove of the scutellum. Lastly, the left and right lateral scales emerge from the edges of the longitudinal groove and expand toward the central line of the axis. As a consequence, morphologically, the bilateral symmetry of the ventral side of the embryo is revealed entirely. Morphogenetically, the coleoptile primordium and apical meristem in maize are similar to the coleoptile (apical cotyledon) and apex formation of the nice embryo, so the coleoptile of the maize embryo can also be considered as an apical cotyledon. The scutellum is a lateral cotyledon. These dimorphic cotyledons of the maize embryo originate from the dorsiventrality of the proper. 3. The true morphological structure of the maize embryo is recognized and its developmental stages are established. A maize embryo is a hypocotyl, in which the apical part is the shoot apex (or plumule) with the coleoptile, the central part consists mainly of the hypocotyl with a lateral cotyledon (scutellum), and the basal part is the radicle with coleorhiza. The left and right lateral scales derived from the scutellum overlap at the ventral side, leaving only two little pores at both ends of the seam from which the coleoptile and coleorhiza can be seen. The four sequential stages of maize embryonic development are as follows: (1) proembryo, stage. This stage covers a period from zygotic cell division to the appearance of the dorsum and ventrum. (2) ventrum rapid differentiation stage. (3) scutellum rapid expansion stage. (4) lateral scale development stage (or embryonic envelope formation stage). 4. To obtain a median longitudinal section perpendicular to the ventral surface is crucial for recognizing the genuine morphological structure of the maize embryo.展开更多
Sexual selection is considered the major cause of sexual dimorphism, but recent observations suggest that natural selection may play a more important role in the evolution of sex differentiation than previously recogn...Sexual selection is considered the major cause of sexual dimorphism, but recent observations suggest that natural selection may play a more important role in the evolution of sex differentiation than previously recognized. Therefore, studying the trade-offs between natural selection and sexual selection is crucial to a better understanding of the ecology underlying the evolution of sexual dimorphism. The freshwater blenny Salaria fluviatilis, a fish inhabiting lakes and rivers around the Mediterranean Sea, displays strong sexual dimorphism in size, shape, and behavior （i.e., larger body and head size for males and higher swimming requirements for females during the reproductive period）. We tested for differences in sexual dimorphism in size and shape between the populations from lake and river habitats with the goal of identifying the trade-offs between natural and sexual se- lection that underlie variations in sexual dimorphism in this species. Our results show i） differences in sexual size dimorphism （SSizeD） in accordance to Rensch＇s rule （i.e., larger individuals in rivers associated with higher SSizeD）, and ii） a decrease in shape differentiation between males and fe- males in lake populations. Together, this suggests that the different environmental conditions between lake and river habitats （e.g., resource limitations, predation pressure, water velocity） affect the relative importance of sexual selection in the display of sexual dimorphism within the species. This study highlights the importance of considering the environmental conditions to which populations are exposed to better understand the ecology underlying the evolution of sexual dimorphism.展开更多
In addition to the loss of motor function,~60% of patients develop pain after spinal cord injury.The cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epice...In addition to the loss of motor function,~60% of patients develop pain after spinal cord injury.The cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic pain.Sprouting can lead to the formation of new connections triggering abnormal sensory transmission.The excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and excitotoxicity.Our previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator tamoxifen.In this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord injury.We hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant sprouting.Male and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical allodynia.Tamoxifen treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent effect.The expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on astrocytes.Female rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased excitatory amino acid transporter-2 expression compared with female rodents.Analyses of peptidergic(calcitonin gene-related peptide-α)and non-peptidergic(isolectin B4)fibers outgrowth in the dorsal horn after spinal cord injury showed an increased calcitonin gene-related peptide-α/isolectin B4 ratio in comparison with sham,suggesting increased receptive fields in the dorsal horn.Although the behavioral assay shows decreased allodynia in tamoxifen-treated female rats,this was not associated with overexpression of glutamate transporters or alterations in the dorsal horn laminae fibers at 28 days post-injury.Our findings provide new evidence of the sexually dimorphic expression of glutamate transporters in the spinal cord.The dimorphic expression revealed in this study provides a therapeutic opportunity for treating chronic pain,an area with a critical need for treatment.展开更多
基金supported by the Guangzhou Municiple Health Commission(2023 C-TS26)the Opening Foundation of Jiangsu Key Laboratory of Neurodegeneration,Nanjing Medical University(KF202202)+1 种基金the Plan on Enhancing Scientific Research in Guangzhou Medical University(02-410-230221XM,GMUCR2024-02025)the Project of Guangzhou Municipal Science and Technology Bureau(2023A03J0835).
文摘Dear Editor,Major depressive disorder(MDD)is associated with a high rate of suicide attempts(SA).Previous reports have identified risk factors for SA in MDD patients,including sex and metabolic disorders[1].However,to our knowledge,the impact of sex differences on the association between body mass index(BMI)status and SA in patients with MDD has not been investigated.Th is study aimed to investigate:1)the sex diff erence in the prevalence of recent SA in Chinese drug-naïve fi rst-episode(DNFE)MDD patients,and 2)the eff ect of sex diff erence on the relationship between higher BMI(overweight or obese)and recent SA.Patients were recruited from the First Clinical Medical College of Shanxi Medical University from January 2015 to December 2017.All patients met the inclusion and exclusion criteria described in previous studies[2].
基金supported by the National Natural Science Foundation of China (Grant No.32171843)the Postgraduate Scientific Research Innovation Project of Hunan Province (Grant No.CX20200696)the Scientific Innovation Fund for Graduate of Central South University of Forestry and Technology (Grant No.CX20201003)。
文摘The mu oil tree(Vernicia montana Lour.) is a dioecious species, but the genetic mechanisms underlying its phenotypic sexual dimorphism are unclear. In this study, we determined two pivotal phases of sex differentiation of mu oil tree via morphological and histological analyses of unisexual flowers:(Ⅰ) differentiation of male or female primordia to produce staminate flowers(SFs) or transient hermaphrodite flowers(HFs),and(Ⅱ) complete abortion of stamens in transient HFs to generate pistillate flowers(PFs). A total of 1621 sex-biased genes were identified by comparative transcriptome analysis which exhibited elevated rates of protein evolution than unbiased genes. The female-biased genes were enriched in the production of defense compounds while male-biased genes were focused on the production of viable pollens. Transcriptomebased analysis revealed that the differentially expressed genes(DEGs) between PFs and SFs in phase Ⅰ involved in abscisic acid(ABA), auxin(AUX), cytokinin(CK), ethylene(ET), and gibberellin(GA) biosynthesis and signaling showed higher expression levels in males than in females in general, whereas the DEGs involved in jasmonic acid(JA) and salicylic acid(SA) pathways displayed opposite expression patterns. Moreover,differentially expressed endogenous ABA, AUX, GAs, JA, and SA exhibited consistent biased expression patterns with the DEGs by UPLC-MSbased analysis. Exogenous application of an anti-ethylene plant growth regulator could promote the development of stamens in PFs and generated HFs. Comparative transcriptomic and hormonal analyses of PFs and SFs in phase Ⅱ indicated an increase in ET concentration when abortion of stamens in PFs occurred. This study suggested that phytohormones play key roles in sex dimorphism and ET may determine the development of stamens in PFs of mu oil tree, which provides an insight into plant sex differentiation mechanisms.
基金supported by grants from the Special Foundation for Basic Work of the Science and Technology Ministry of China (2022FY100500-2)National Natural Science Foundation of China (31470471)+2 种基金Hainan Key Program of Science and Technology (ZDXM20110008)Hainan Specially Supporting Discipline of ZoologyWenzhou Ecological Park Research Project。
文摘We studied sexual dimorphism in body size and shape and female reproductive characteristics in the Hainan Water Skink(Tropidophorus hainanus)from Hainan,South China.In our sample the largest female and male were 61.1 and 55.2 mm snout-vent length(SVL),respectively.The mean SVL was larger in adult females(52.0 mm)than in adult males(48.3 mm).Juveniles were sexually dimorphic in head length but not in other examined morphological variables.Adult males were longer in head length and shorter in abdomen length and fore-limb length than adult females of the same SVL.Ontogenetic shifts in sexual dimorphism in body shape were evident,as revealed by the fact that morphological differences between the sexes were more pronounced in adults than in juveniles.Females produced a single litter of 3–6 offspring per season from early August to early September.Litter size,litter mass and offspring(neonate)mass were positively related to female SVL.Neonate mass was independent of relative fecundity.From the above findings we draw three main conclusions.First,females are the larger sex in T.hainanus,and sexual dimorphism in body shape is more pronounced in adults than in juveniles.Second,larger female T.hainanus produce more and larger offspring and thus heavier litters than smaller ones.Third,the offspring size-number trade-off does is not evident in T.hainanus.
文摘The Japanese Genji firefly Nipponoluciola cruciata is famous for geographic variation in flash pattern. Such geographic variation has also been well studied in terms of ecology and molecular phylogeny. However, there are very few studies on geographic variation in morphology of this species. This study focused on morphological characteristics of males of this species in Yamanashi and Gunma Prefectures separated by the Kanto Mountains in central Japan. Previous studies have shown that this species in the two prefectures exhibits different genetic features as well as different flash patterns. This study aimed to explore morphological characteristics of males of this species and performed multivariate analysis using measurements previously published in the literature. As a result, allometric analysis between body length and elytra width suggested that this species exhibits different allometric patterns between the two prefectures. Moreover, cluster analysis of measurements of genitalia suggested that this species is completely separated into two different groups between the two prefectures. These results suggest the importance of further morphological studies to clarify the divergence of this species.
基金supported by the National Natural Science Foundation of China (Grant No. 30400047)the Training Fund of Northeast Normal University Scientific Innovation Project (Grant No. 07013)the Jilin Provincial Science and Technology Department (Grant No. 20070558 and 20090575)
文摘Fisher's theory predicts equal sex ratios at the end of parental care if the cost associated with raising offspring of each sex is equal.However,sex ratios have important evolutionary consequences and are often biased for many factors.Reported sex ratios are often biased in raptors,which display various degrees of reversed sexual dimorphism,but there seems no consistent pattern in their offspring sex ratios.In this study,we investigated the offspring sex ratio of the Eurasian Kestrel(Falco tinnunculus) and tested whether the patterns of biased sex ratios were related to laying order,egg mass,hatching order,laying date or clutch size.The brood sex ratio of the Eurasian Kestrel(male) in eggs was 47.0%,not statistically biased from 0.5,but in fledglings it was 40.8%,significantly biased from 0.5(p = 0.029).At population level,both primary and secondary sex ratios did not depart from parity.We found that clutch size and egg mass affected the secondary brood sex ratio,i.e.,the larger the clutch size,the larger the number of males and eggs producing sons were heavier than eggs producing daughters.Laying date affected both the primary and secondary sex ratios,and laying earlier is associated with a greater proportion of males.
文摘A series of new cognitions on the morphogenesis of maize ( Zea mays L.) embryo have been obtained with scanning electron microscopy and semi-thin section techniques. 1. The proembryo. The proembryo from zygotic cell divisions may be divided into three parts: proper, hypoblast and suspensor. The suspensor is short and small, and only exists transiently. As to the hypoblast there is a growth belt, which promotes elongation of the hypoblast. Eventually the upper portion of the hypoblast contributes to the formation of the coleorhiza and the remainder dries up, sticking to the end of the coleorhiza. 2. The maize embryo possesses dorsiventrality and cotyledon dimorphism. During early proembryo stage, the dorsiventrality appears in the proper of the embryo. On the ventral side, the cells are small with dense cytoplasm and few vacuoles. On the dorsal side, the cells are larger with lower cytoplasmic density and have more vacuoles. During later proembryo stage, the proper develops into two parts: the ventrum and the dorsurn. The ventrum rises up from the center of the ventral side. The dorsurn is composed of the marginal area of the ventral side and the whole dorsal side of the proper. During young embryo development, the ventrum differentiates into the coleoptile, apical meristem, hypocotyl, radicle and the main part of the coleorhiza. What is more important, the emergence of coleoptile primordium and radicular initials occur at the axis of the proper, then the coleoptile primordium expands from its two ends toward left and right to form a ring, and the endogenous radicular initials expand in all directions to form a conical radicular tip. All these morphogenetic activities of the ventrum follow a bilateral symmetrical pattern. The dorsurn forms the scutellum. primordium. Then the scutellum primordium, expands rapidly toward the left, right, front and back, while thickening itself, so as to make all components originating from the ventrum become hidden in the longitudinal groove of the scutellum. Lastly, the left and right lateral scales emerge from the edges of the longitudinal groove and expand toward the central line of the axis. As a consequence, morphologically, the bilateral symmetry of the ventral side of the embryo is revealed entirely. Morphogenetically, the coleoptile primordium and apical meristem in maize are similar to the coleoptile (apical cotyledon) and apex formation of the nice embryo, so the coleoptile of the maize embryo can also be considered as an apical cotyledon. The scutellum is a lateral cotyledon. These dimorphic cotyledons of the maize embryo originate from the dorsiventrality of the proper. 3. The true morphological structure of the maize embryo is recognized and its developmental stages are established. A maize embryo is a hypocotyl, in which the apical part is the shoot apex (or plumule) with the coleoptile, the central part consists mainly of the hypocotyl with a lateral cotyledon (scutellum), and the basal part is the radicle with coleorhiza. The left and right lateral scales derived from the scutellum overlap at the ventral side, leaving only two little pores at both ends of the seam from which the coleoptile and coleorhiza can be seen. The four sequential stages of maize embryonic development are as follows: (1) proembryo, stage. This stage covers a period from zygotic cell division to the appearance of the dorsum and ventrum. (2) ventrum rapid differentiation stage. (3) scutellum rapid expansion stage. (4) lateral scale development stage (or embryonic envelope formation stage). 4. To obtain a median longitudinal section perpendicular to the ventral surface is crucial for recognizing the genuine morphological structure of the maize embryo.
文摘Sexual selection is considered the major cause of sexual dimorphism, but recent observations suggest that natural selection may play a more important role in the evolution of sex differentiation than previously recognized. Therefore, studying the trade-offs between natural selection and sexual selection is crucial to a better understanding of the ecology underlying the evolution of sexual dimorphism. The freshwater blenny Salaria fluviatilis, a fish inhabiting lakes and rivers around the Mediterranean Sea, displays strong sexual dimorphism in size, shape, and behavior （i.e., larger body and head size for males and higher swimming requirements for females during the reproductive period）. We tested for differences in sexual dimorphism in size and shape between the populations from lake and river habitats with the goal of identifying the trade-offs between natural and sexual se- lection that underlie variations in sexual dimorphism in this species. Our results show i） differences in sexual size dimorphism （SSizeD） in accordance to Rensch＇s rule （i.e., larger individuals in rivers associated with higher SSizeD）, and ii） a decrease in shape differentiation between males and fe- males in lake populations. Together, this suggests that the different environmental conditions between lake and river habitats （e.g., resource limitations, predation pressure, water velocity） affect the relative importance of sexual selection in the display of sexual dimorphism within the species. This study highlights the importance of considering the environmental conditions to which populations are exposed to better understand the ecology underlying the evolution of sexual dimorphism.
基金supported by COBRE(P30GM149367)the Puerto Rico Science&Technology Trust(2022-00125)+1 种基金MBRS-RISE Program(R25 GM061838)SC1GM144032 program(all to JDM)。
文摘In addition to the loss of motor function,~60% of patients develop pain after spinal cord injury.The cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic pain.Sprouting can lead to the formation of new connections triggering abnormal sensory transmission.The excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and excitotoxicity.Our previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator tamoxifen.In this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord injury.We hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant sprouting.Male and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical allodynia.Tamoxifen treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent effect.The expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on astrocytes.Female rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased excitatory amino acid transporter-2 expression compared with female rodents.Analyses of peptidergic(calcitonin gene-related peptide-α)and non-peptidergic(isolectin B4)fibers outgrowth in the dorsal horn after spinal cord injury showed an increased calcitonin gene-related peptide-α/isolectin B4 ratio in comparison with sham,suggesting increased receptive fields in the dorsal horn.Although the behavioral assay shows decreased allodynia in tamoxifen-treated female rats,this was not associated with overexpression of glutamate transporters or alterations in the dorsal horn laminae fibers at 28 days post-injury.Our findings provide new evidence of the sexually dimorphic expression of glutamate transporters in the spinal cord.The dimorphic expression revealed in this study provides a therapeutic opportunity for treating chronic pain,an area with a critical need for treatment.
