The sexually dimorphic expression of glutamate transporters and their implication in pain after spinal cord injury  

作　　者：Jennifer M.Colón-Mercado Aranza I.Torrado-Tapias Iris K.Salgado Jose M.Santiago Samuel E.Ocasio Rivera Dina P.Bracho-Rincon Luis H.Pagan Rivera Jorge D.Miranda 

机构地区：[1]Department of Physiology,University of Puerto Rico,Medical Sciences Campus,San Juan,PR,USA [2]National Institutes of Health,National Human Genome Research Institute,Bethesda,MD,USA [3]Universidad Central del Caribe,School of Medicine,Bayamón,PR,USA [4]University of Puerto Rico,Carolina Campus,Carolina,PR,USA [5]Institute of Neurobiology,San Juan,PR,USA

出　　处：《Neural Regeneration Research》2025年第11期3317-3329,共13页中国神经再生研究（英文版）

基　　金：supported by COBRE(P30GM149367);the Puerto Rico Science&Technology Trust(2022-00125);MBRS-RISE Program(R25 GM061838);SC1GM144032 program(all to JDM)。

摘　　要：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 expressi

关 键 词：ALLODYNIA central neuropathic pain EAAT-1/GLAST EAAT-2/GLT-1 glutamate transporters selective estrogen receptor modulator sexual dimorphism spinal cord injury TRAUMA 

分 类 号：R651.2[医药卫生—外科学]