Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic ...Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3(NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.展开更多
The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA), also called ecstasy, is a neurotoxin widely consumed among young people that has increased in recent years because it is a recreational drug, of whi...The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA), also called ecstasy, is a neurotoxin widely consumed among young people that has increased in recent years because it is a recreational drug, of which immediate effects are known such as a greater sensation of well-being, extroversion, increased sensory perception. However, its long-term effects have been described very little in the medical literature, including damage to the heart, central nervous system, kidney, etc. One of its little-known effects is hepatotoxicity, of which few cases are known associated with fulminant hepatitis, which is a rapidly deteriorating condition that is generally associated with a syndrome of multiple organ dysfunction and death. Therefore, it is very important to know this type of damage in the short and long term. The following case is of a 39-year-old man who came to our service due to jaundice syndrome and the only history of MDMA consumption, who as the days went by met the criteria for fulminant liver failure, with damage to multiple organs (organ dysfunction syndrome).展开更多
Aim p53 up-regulated modulator of apoptosis （PUMA） is a known apoptosis inducer; however its role in microglial survival remains poorly understood. In addition to the classical transcription factor p53, microRNA- ...Aim p53 up-regulated modulator of apoptosis （PUMA） is a known apoptosis inducer; however its role in microglial survival remains poorly understood. In addition to the classical transcription factor p53, microRNA- 143 （miR-143） is involved in PUMA expression at the post-transcriptional level. Furthermore, they identify unique roles of miR-143/PUMA in mediating microglial survival via the regulation of apoptosis and autophagy interplay. Results Blockage of autophagy accelerated methamphetamine-induced apoptosis, whereas the induction of autoph- agy attenuated the decrease in microglial survival. Moreover, anti-miR-143-dependent PUMA up-regulation re- versed the methamphetamine-induced decrease in microglial survival via the regulation of apoptosis and autophagy. The in vivo relevance of these findings was confirmed in mouse models, which demonstrated that the microinjection of anti-miR-143 into the hippocampus ameliorated the methamphetamine-induced decrease in microglia as well as that observed in heterozygous miR-143 ^＋/- mice. Conclusion These findings provided new insight for the specific contributions of miR-143/PUMA to microglial survival in the context of drug abuse.展开更多
The relapse of methamphetamine (meth) is associated with decision-making dysfunction. The present study aims to investigate theimpact of different emotions on the decision-making behavior of meth users. We used 2 (gen...The relapse of methamphetamine (meth) is associated with decision-making dysfunction. The present study aims to investigate theimpact of different emotions on the decision-making behavior of meth users. We used 2 (gender: male, female) × 3 (emotion:positive, negative, neutral) × 5 (block: 1, 2, 3, 4, 5) mixed experiment design. The study involved 168 meth users who weredivided into three groups: positive emotion, negative emotion and neutral emotion group, and tested by the emotional IowaGambling Task (IGT). The IGT performance of male users exhibited a decreasing trend from Block 1 to Block 3. Female methusers in positive emotion had the best performance in IGT than females in the other two groups. In positive emotion, the IGTperformance of female meth users was significantly better than that of men. Female meth users in positive emotion had betterdecision-making than those in negative or neutral emotion. Female meth users in positive emotion had better decision-makingperformance than males in positive emotion. In negative and neutral emotions, there was no significant gender difference indecision-making.展开更多
Background Methamphetamine (MA) is one of the most commonly abused illicit psychostimulant drugs and MA use disorder constitutes a universal health concern across the world. Despite many intervention approaches to MA ...Background Methamphetamine (MA) is one of the most commonly abused illicit psychostimulant drugs and MA use disorder constitutes a universal health concern across the world. Despite many intervention approaches to MA use disorder, the indicator of addiction severity is mainly limited to subjective craving score to drug-related cues, which is influenced by many factors such as social approval and self-masking. Aim The present study investigates whether self-reported craving for drug use in response to MA cues is a reliable indicator for addiction severity in MA users, and then tests the validity of the cue-induced attention bias test in addiction severity assessment. Methods Fifty-two male MA users completed the cueinduced craving test and attention bias task, and were required to report clinical characteristics of addiction severity. For the attention bias test, subjects were required to discriminate the letter superimposed onto MA userelated or neutral scenes. The reaction time delay during MA-use condition relative to neutral condition was used as an index of the attention bias. Results The results showed that 24 of the 52 MA users rated non-zero in cue-induced craving test, and they showed a significant attention bias to drug-related pictures. However, the other 28 users who rated zero in cue-induced craving evaluation showed a similar attention bias to drug-related cues. In addition, the attention bias to MA use-related cues was significantly and positively correlated with the clinical indexes of addiction severity, but the relationship was absent between subjective craving evaluation and the indexes of addiction severity. Conclusion These results suggest that attention bias to MA cues may be a more reliable indicator than experiential craving report, especially when subjective craving is measured in the compulsory rehabilitation centre.展开更多
Methamphetamine is one of the most prevalent drugs abused in the world.Methamphetamine abusers usually present with hyperpyrexia (39℃),hallucination and other psychiatric symptoms.However,the detailed mechanism under...Methamphetamine is one of the most prevalent drugs abused in the world.Methamphetamine abusers usually present with hyperpyrexia (39℃),hallucination and other psychiatric symptoms.However,the detailed mechanism underlying its neurotoxic action remains elusive.This study investigated the effects of methamphetamine + 39℃ on primary cortical neurons from the cortex of embryonic Sprague-Dawley rats.Primary cortex neurons were exposed to 1 mM methamphetamine + 39℃.Propidium iodide staining and lactate dehydrogenase release detection showed that methamphetamine + 39℃ triggered obvious necrosis-like death in cultured primary cortical neurons,which could be partially inhibited by receptor-interacting protein-1 (RIP1) inhibitor Necrostatin-1 partially.Western blot assay results showed that there were increases in the expressions of receptor-interacting protein-3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the primary cortical neurons treated with 1 mM methamphetamine + 39℃ for 3 hours.After pre-treatment with RIP3 inhibitor GSK’872,propidium iodide staining and lactate dehydrogenase release detection showed that neuronal necrosis rate was significantly decreased;RIP3 and MLKL protein expression significantly decreased.Immunohistochemistry staining results also showed that the expressions of RIP3 and MLKL were up-regulated in brain specimens from humans who had died of methamphetamine abuse.Taken together,the above results suggest that methamphetamine + 39℃ can induce RIP3/MLKL regulated necroptosis,thereby resulting in neurotoxicity.The study protocol was approved by the Medical Ethics Committee of the Third Xiangya Hospital of Central South University,China (approval numbers: 2017-S026 and 2017-S033) on March 7,2017.展开更多
Objective To demonstrate the myocardial lesion associated with long-term administration of methamphetamine in rats. Methods The experimental models of intoxication of methamphetamine were established in Sprague-Dawle...Objective To demonstrate the myocardial lesion associated with long-term administration of methamphetamine in rats. Methods The experimental models of intoxication of methamphetamine were established in Sprague-Dawley rats. Methamphetamine hydrochloride （3 mg·kg^-1·d^-1） was subcutaneously injected to rats in methamphetarnine-treated group （n = 16）, and normal saline at the same dose was injected to rats in control group （n = 16）. After 1 week and 8 weeks of injection, 8 rats in each group were sacrificed and their hearts were examined with light microscopy and electron microscopy, respectively. Results After 1 week of methamphetamine exposure, loci of contraction band and cellular degeneration were present in subendocardial myocardium. Cellular degeneration, myocytolysis, and contraction band necrosis became prominent and extensive in methamphetamine-treated rats after 8 weeks. Hypertrophy, intracellular vacuolization, and fibrosis were also observed. The ultrastructural feature showed marked swelling and degeneration of mitochondria, enlargement of sarcoplasmic reticulum, and dissolution of myofilaments. No obvious cardiac myocyte lesions were observed in rats of control group. Conclusion Methamphetamine abuse daily for a long time may result in an increased risk of cardiovascular lesions similar to cardiomyopatby.展开更多
Methamphetamine is an amphetamine-type psychostimulant that can damage dopaminergic neurons and cause characteristic pathological changes similar to neurodegenerative diseases such as Parkinson's disease. However,...Methamphetamine is an amphetamine-type psychostimulant that can damage dopaminergic neurons and cause characteristic pathological changes similar to neurodegenerative diseases such as Parkinson's disease. However, its specific mechanism of action is still unclear. In the present study, we established a Parkinson's disease pathology model by exposing SH-SY5 Y cells and C57 BL/6 J mice to methamphetamine. In vitro experiments were performed with 0, 0.5, 1.0, 1.5, 2.0 or 2.5 mM methamphetamine for 24 hours or 2.0 mM methamphetamine for 0-, 2-, 4-, 8-, 16-, and 24-hour culture of SH-SY5 Y cells. Additional experimental groups of SH-SY5 Y cells were administered a nitric oxide inhibitor, 0.1 mM N-nitro-L-arginine, 1 hour before exposure to 2.0 mM methamphetamine for 24 hours. In vivo experiments: C57 BL/6 J mice were intraperitoneally injected with N-nitro-L-arginine(8 mg/kg), eight times, at intervals of 12 hours. Methamphetamine 15 mg/kg was intraperitoneally injected eight times, at intervals of 12 hours, but 0.5-hour after each N-nitro-L-arginine injection in the combined group. Western blot assay was used to determine the expression of nitric oxide synthase, α-synuclein(α-Syn), 5 G4, nitrated α-synuclein at the residue Tyr39(nT39 α-Syn), cleaved caspase-3, and cleaved poly ADP-ribose polymerase(PARP) in cells and mouse brain tissue. Immunofluorescence staining was conducted to measure the positive reaction of NeuN, nT39 α-Syn and 5 G4. Enzyme linked immunosorbent assay was performed to determine the dopamine levels in the mouse brain. After methamphetamine exposure, α-Syn expression increased; the aggregation of α-Syn 5 G4 increased; nT39 α-Syn, nitric oxide synthase, cleaved caspase-3, and cleaved PARP expression increased in the cultures of SH-SY5 Y cells and in the brains of C57 BL/6 J mice; and dopamine levels were reduced in the mouse brain. These changes were markedly reduced when N-nitro-L-arginine was administered with methamphetamine in both SH-SY5 Y cells and C57 BL/6 J mice. These results suggest that nT39 α-Syn aggregation is involved in methamphetamine neurotoxicity.展开更多
The use of ＂bath salts＂ or other new psychoactive substances,otherwise known as ＂legal highs＂,is increasing.Illicit drug use during pregnancy is not uncommon.Nevertheless,literature reporting bath salts and their ...The use of ＂bath salts＂ or other new psychoactive substances,otherwise known as ＂legal highs＂,is increasing.Illicit drug use during pregnancy is not uncommon.Nevertheless,literature reporting bath salts and their effect on pregnancy is scant.Besides,there seems to be no literature about bath salts and conduct of general anesthesia.This case report describes a general anesthetic for the surgical delivery of an infant to a woman under the acute influence of bath salts and methamphetamines.展开更多
This study examined the neuroprotective effect of cluster of differentiation molecule 200 （CD200） against methamphetamine （METH）-induced neurotoxicity. In the in vitro experiment, neuron-microglia cultures were tr...This study examined the neuroprotective effect of cluster of differentiation molecule 200 （CD200） against methamphetamine （METH）-induced neurotoxicity. In the in vitro experiment, neuron-microglia cultures were treated with METH （20 μmol/L）, METH （20 μmol/L）＋CD200-Fc （10 μg/mL） or CD200-Fc （10 μg/mL）. Those untreated served as control. Microglia activation expressed as the ratio of MHC-Ⅱ/CD11b was assessed by flow cytometry. The cytokines （IL-1β, TNF-α） secreted by activated microglia were detected by enzyme-linked immunosorbent assay （ELISA）. In the in vivo experiment, 40 SD rats were divided into control, METH, METH＋CD200-Fc and CD200-Fc groups at random. Rats were intraperitoneally injected with METH （15 mg/kg 8 times at 12 h interval） in METH group, with METH （administered as the same dose and time as the METH group） and CD200-Fc （1 mg/kg at day 0, 2, 4 after METH injection） in METH＋CD200-Fc group, with CD200-Fc （1 mg/kg injected as the same time as the METH＋CD200-Fc group） or with physiological saline solution in the control group. The level of striatal dopamine （DA） in rats was measured by high-performance liquid chromatography （HPLC）. The microglial cells were immunohistochemically detected for the expression of Iba-1, a marker for microglial activation. The results showed that METH could increase the microglia activation in the neuron-microglia cultures and elevate the secretion of IL-1β and TNF-α, which could be attenuated by CD200-Fc. Moreover, CD200-Fc could partially reverse the striatal DA depletion induced by METH and reduce the number of activated microglia, i.e. Iba-1-positive cells. It was concluded that CD200 may have neuroprotective effects against METH-induced neurotoxicity by inhibiting microglial activation and reversing DA depletion in striatum.展开更多
基金supported by the National Natural Science Foundation of China,No.81971246 (to TM)Opening Foundation of Jiangsu Key Laboratory of Neurodegeneration,Nanjing Medical University,No.KF202204 (to LZ and SF)。
文摘Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3(NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.
文摘The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA), also called ecstasy, is a neurotoxin widely consumed among young people that has increased in recent years because it is a recreational drug, of which immediate effects are known such as a greater sensation of well-being, extroversion, increased sensory perception. However, its long-term effects have been described very little in the medical literature, including damage to the heart, central nervous system, kidney, etc. One of its little-known effects is hepatotoxicity, of which few cases are known associated with fulminant hepatitis, which is a rapidly deteriorating condition that is generally associated with a syndrome of multiple organ dysfunction and death. Therefore, it is very important to know this type of damage in the short and long term. The following case is of a 39-year-old man who came to our service due to jaundice syndrome and the only history of MDMA consumption, who as the days went by met the criteria for fulminant liver failure, with damage to multiple organs (organ dysfunction syndrome).
文摘Aim p53 up-regulated modulator of apoptosis （PUMA） is a known apoptosis inducer; however its role in microglial survival remains poorly understood. In addition to the classical transcription factor p53, microRNA- 143 （miR-143） is involved in PUMA expression at the post-transcriptional level. Furthermore, they identify unique roles of miR-143/PUMA in mediating microglial survival via the regulation of apoptosis and autophagy interplay. Results Blockage of autophagy accelerated methamphetamine-induced apoptosis, whereas the induction of autoph- agy attenuated the decrease in microglial survival. Moreover, anti-miR-143-dependent PUMA up-regulation re- versed the methamphetamine-induced decrease in microglial survival via the regulation of apoptosis and autophagy. The in vivo relevance of these findings was confirmed in mouse models, which demonstrated that the microinjection of anti-miR-143 into the hippocampus ameliorated the methamphetamine-induced decrease in microglia as well as that observed in heterozygous miR-143 ^＋/- mice. Conclusion These findings provided new insight for the specific contributions of miR-143/PUMA to microglial survival in the context of drug abuse.
基金supported by grants from the National Social Science Foundation of China(19BGL230)the Key Project of Social Science Planning in Jiangxi Province(23JY01).
文摘The relapse of methamphetamine (meth) is associated with decision-making dysfunction. The present study aims to investigate theimpact of different emotions on the decision-making behavior of meth users. We used 2 (gender: male, female) × 3 (emotion:positive, negative, neutral) × 5 (block: 1, 2, 3, 4, 5) mixed experiment design. The study involved 168 meth users who weredivided into three groups: positive emotion, negative emotion and neutral emotion group, and tested by the emotional IowaGambling Task (IGT). The IGT performance of male users exhibited a decreasing trend from Block 1 to Block 3. Female methusers in positive emotion had the best performance in IGT than females in the other two groups. In positive emotion, the IGTperformance of female meth users was significantly better than that of men. Female meth users in positive emotion had betterdecision-making than those in negative or neutral emotion. Female meth users in positive emotion had better decision-makingperformance than males in positive emotion. In negative and neutral emotions, there was no significant gender difference indecision-making.
基金National Natural Science Foundation of China (grant no. 3187110331671164).
文摘Background Methamphetamine (MA) is one of the most commonly abused illicit psychostimulant drugs and MA use disorder constitutes a universal health concern across the world. Despite many intervention approaches to MA use disorder, the indicator of addiction severity is mainly limited to subjective craving score to drug-related cues, which is influenced by many factors such as social approval and self-masking. Aim The present study investigates whether self-reported craving for drug use in response to MA cues is a reliable indicator for addiction severity in MA users, and then tests the validity of the cue-induced attention bias test in addiction severity assessment. Methods Fifty-two male MA users completed the cueinduced craving test and attention bias task, and were required to report clinical characteristics of addiction severity. For the attention bias test, subjects were required to discriminate the letter superimposed onto MA userelated or neutral scenes. The reaction time delay during MA-use condition relative to neutral condition was used as an index of the attention bias. Results The results showed that 24 of the 52 MA users rated non-zero in cue-induced craving test, and they showed a significant attention bias to drug-related pictures. However, the other 28 users who rated zero in cue-induced craving evaluation showed a similar attention bias to drug-related cues. In addition, the attention bias to MA use-related cues was significantly and positively correlated with the clinical indexes of addiction severity, but the relationship was absent between subjective craving evaluation and the indexes of addiction severity. Conclusion These results suggest that attention bias to MA cues may be a more reliable indicator than experiential craving report, especially when subjective craving is measured in the compulsory rehabilitation centre.
基金funded by the National Natural Science Foundation of China,No.81971891(to KX),81571939(to KX),81772134(to KX),81772024(to JY),and 81860781(to FXL)the Key Research and Development Program of Hunan Province of China,No.2018SK2091(to KX)+1 种基金the Natural Science Foundation of Hunan Province of China,No.2017JJ2339(to JY)the Wu Jie-Ping Medical Foundation of the Minister of Health of China,No.320.6750.14118(to KX)
文摘Methamphetamine is one of the most prevalent drugs abused in the world.Methamphetamine abusers usually present with hyperpyrexia (39℃),hallucination and other psychiatric symptoms.However,the detailed mechanism underlying its neurotoxic action remains elusive.This study investigated the effects of methamphetamine + 39℃ on primary cortical neurons from the cortex of embryonic Sprague-Dawley rats.Primary cortex neurons were exposed to 1 mM methamphetamine + 39℃.Propidium iodide staining and lactate dehydrogenase release detection showed that methamphetamine + 39℃ triggered obvious necrosis-like death in cultured primary cortical neurons,which could be partially inhibited by receptor-interacting protein-1 (RIP1) inhibitor Necrostatin-1 partially.Western blot assay results showed that there were increases in the expressions of receptor-interacting protein-3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the primary cortical neurons treated with 1 mM methamphetamine + 39℃ for 3 hours.After pre-treatment with RIP3 inhibitor GSK’872,propidium iodide staining and lactate dehydrogenase release detection showed that neuronal necrosis rate was significantly decreased;RIP3 and MLKL protein expression significantly decreased.Immunohistochemistry staining results also showed that the expressions of RIP3 and MLKL were up-regulated in brain specimens from humans who had died of methamphetamine abuse.Taken together,the above results suggest that methamphetamine + 39℃ can induce RIP3/MLKL regulated necroptosis,thereby resulting in neurotoxicity.The study protocol was approved by the Medical Ethics Committee of the Third Xiangya Hospital of Central South University,China (approval numbers: 2017-S026 and 2017-S033) on March 7,2017.
基金Supported by Medical Scientific Research Foundation of Hubei Province (JX3B55)
文摘Objective To demonstrate the myocardial lesion associated with long-term administration of methamphetamine in rats. Methods The experimental models of intoxication of methamphetamine were established in Sprague-Dawley rats. Methamphetamine hydrochloride （3 mg·kg^-1·d^-1） was subcutaneously injected to rats in methamphetarnine-treated group （n = 16）, and normal saline at the same dose was injected to rats in control group （n = 16）. After 1 week and 8 weeks of injection, 8 rats in each group were sacrificed and their hearts were examined with light microscopy and electron microscopy, respectively. Results After 1 week of methamphetamine exposure, loci of contraction band and cellular degeneration were present in subendocardial myocardium. Cellular degeneration, myocytolysis, and contraction band necrosis became prominent and extensive in methamphetamine-treated rats after 8 weeks. Hypertrophy, intracellular vacuolization, and fibrosis were also observed. The ultrastructural feature showed marked swelling and degeneration of mitochondria, enlargement of sarcoplasmic reticulum, and dissolution of myofilaments. No obvious cardiac myocyte lesions were observed in rats of control group. Conclusion Methamphetamine abuse daily for a long time may result in an increased risk of cardiovascular lesions similar to cardiomyopatby.
基金supported by the National Natural Science Foundation of China,No.81373240(to PMQ)and 81671865(to PMQ)
文摘Methamphetamine is an amphetamine-type psychostimulant that can damage dopaminergic neurons and cause characteristic pathological changes similar to neurodegenerative diseases such as Parkinson's disease. However, its specific mechanism of action is still unclear. In the present study, we established a Parkinson's disease pathology model by exposing SH-SY5 Y cells and C57 BL/6 J mice to methamphetamine. In vitro experiments were performed with 0, 0.5, 1.0, 1.5, 2.0 or 2.5 mM methamphetamine for 24 hours or 2.0 mM methamphetamine for 0-, 2-, 4-, 8-, 16-, and 24-hour culture of SH-SY5 Y cells. Additional experimental groups of SH-SY5 Y cells were administered a nitric oxide inhibitor, 0.1 mM N-nitro-L-arginine, 1 hour before exposure to 2.0 mM methamphetamine for 24 hours. In vivo experiments: C57 BL/6 J mice were intraperitoneally injected with N-nitro-L-arginine(8 mg/kg), eight times, at intervals of 12 hours. Methamphetamine 15 mg/kg was intraperitoneally injected eight times, at intervals of 12 hours, but 0.5-hour after each N-nitro-L-arginine injection in the combined group. Western blot assay was used to determine the expression of nitric oxide synthase, α-synuclein(α-Syn), 5 G4, nitrated α-synuclein at the residue Tyr39(nT39 α-Syn), cleaved caspase-3, and cleaved poly ADP-ribose polymerase(PARP) in cells and mouse brain tissue. Immunofluorescence staining was conducted to measure the positive reaction of NeuN, nT39 α-Syn and 5 G4. Enzyme linked immunosorbent assay was performed to determine the dopamine levels in the mouse brain. After methamphetamine exposure, α-Syn expression increased; the aggregation of α-Syn 5 G4 increased; nT39 α-Syn, nitric oxide synthase, cleaved caspase-3, and cleaved PARP expression increased in the cultures of SH-SY5 Y cells and in the brains of C57 BL/6 J mice; and dopamine levels were reduced in the mouse brain. These changes were markedly reduced when N-nitro-L-arginine was administered with methamphetamine in both SH-SY5 Y cells and C57 BL/6 J mice. These results suggest that nT39 α-Syn aggregation is involved in methamphetamine neurotoxicity.
文摘The use of ＂bath salts＂ or other new psychoactive substances,otherwise known as ＂legal highs＂,is increasing.Illicit drug use during pregnancy is not uncommon.Nevertheless,literature reporting bath salts and their effect on pregnancy is scant.Besides,there seems to be no literature about bath salts and conduct of general anesthesia.This case report describes a general anesthetic for the surgical delivery of an infant to a woman under the acute influence of bath salts and methamphetamines.
基金supported by grants from the National Natural Science Foundation of China(No.30572090 and No.30872918)
文摘This study examined the neuroprotective effect of cluster of differentiation molecule 200 （CD200） against methamphetamine （METH）-induced neurotoxicity. In the in vitro experiment, neuron-microglia cultures were treated with METH （20 μmol/L）, METH （20 μmol/L）＋CD200-Fc （10 μg/mL） or CD200-Fc （10 μg/mL）. Those untreated served as control. Microglia activation expressed as the ratio of MHC-Ⅱ/CD11b was assessed by flow cytometry. The cytokines （IL-1β, TNF-α） secreted by activated microglia were detected by enzyme-linked immunosorbent assay （ELISA）. In the in vivo experiment, 40 SD rats were divided into control, METH, METH＋CD200-Fc and CD200-Fc groups at random. Rats were intraperitoneally injected with METH （15 mg/kg 8 times at 12 h interval） in METH group, with METH （administered as the same dose and time as the METH group） and CD200-Fc （1 mg/kg at day 0, 2, 4 after METH injection） in METH＋CD200-Fc group, with CD200-Fc （1 mg/kg injected as the same time as the METH＋CD200-Fc group） or with physiological saline solution in the control group. The level of striatal dopamine （DA） in rats was measured by high-performance liquid chromatography （HPLC）. The microglial cells were immunohistochemically detected for the expression of Iba-1, a marker for microglial activation. The results showed that METH could increase the microglia activation in the neuron-microglia cultures and elevate the secretion of IL-1β and TNF-α, which could be attenuated by CD200-Fc. Moreover, CD200-Fc could partially reverse the striatal DA depletion induced by METH and reduce the number of activated microglia, i.e. Iba-1-positive cells. It was concluded that CD200 may have neuroprotective effects against METH-induced neurotoxicity by inhibiting microglial activation and reversing DA depletion in striatum.
