Methamphetamine Inhibits the Glucose Uptake by Human Neurons and Astrocytes: Stabilization by Acetyl-L-Carnitine
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{"title"=>"Methamphetamine Inhibits the Glucose Uptake by Human Neurons and Astrocytes: Stabilization by Acetyl-L-Carnitine", "type"=>"journal", "authors"=>[{"first_name"=>"P. M.", "last_name"=>"Abdul Muneer"}, {"first_name"=>"Saleena", "last_name"=>"Alikunju"}, {"first_name"=>"Adam M.", "last_name"=>"Szlachetka"}, {"first_name"=>"James", "last_name"=>"Haorah"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"1932-6203", "doi"=>"10.1371/journal.pone.0019258", "pmid"=>"21556365"}, "id"=>"f0e1eea3-e9cc-3199-838c-f7bae10e4e45", "abstract"=>"Methamphetamine (METH), an addictive psycho-stimulant drug exerts euphoric effects on users and abusers. It is also known to cause cognitive impairment and neurotoxicity. Here, we hypothesized that METH exposure impairs the glucose uptake and metabolism in human neurons and astrocytes. Deprivation of glucose is expected to cause neurotoxicity and neuronal degeneration due to depletion of energy. We found that METH exposure inhibited the glucose uptake by neurons and astrocytes, in which neurons were more sensitive to METH than astrocytes in primary culture. Adaptability of these cells to fatty acid oxidation as an alternative source of energy during glucose limitation appeared to regulate this differential sensitivity. Decrease in neuronal glucose uptake by METH was associated with reduction of glucose transporter protein-3 (GLUT3). Surprisingly, METH exposure showed biphasic effects on astrocytic glucose uptake, in which 20 µM increased the uptake while 200 µM inhibited glucose uptake. Dual effects of METH on glucose uptake were paralleled to changes in the expression of astrocytic glucose transporter protein-1 (GLUT1). The adaptive nature of astrocyte to mitochondrial β-oxidation of fatty acid appeared to contribute the survival of astrocytes during METH-induced glucose deprivation. This differential adaptive nature of neurons and astrocytes also governed the differential sensitivity to the toxicity of METH in these brain cells. The effect of acetyl-L-carnitine for enhanced production of ATP from fatty oxidation in glucose-free culture condition validated the adaptive nature of neurons and astrocytes. These findings suggest that deprivation of glucose-derived energy may contribute to neurotoxicity of METH abusers.", "link"=>"http://www.mendeley.com/research/methamphetamine-inhibits-glucose-uptake-human-neurons-astrocytes-stabilization-acetyllcarnitine", "reader_count"=>26, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>3, "Researcher"=>6, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>2, "Student > Master"=>5, "Other"=>1, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>3, "Researcher"=>6, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>2, "Student > Master"=>5, "Other"=>1, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>2, "Unspecified"=>2, "Agricultural and Biological Sciences"=>11, "Medicine and Dentistry"=>5, "Pharmacology, Toxicology and Pharmaceutical Science"=>2, "Sports and Recreations"=>1, "Chemistry"=>1, "Psychology"=>2}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Chemistry"=>{"Chemistry"=>1}, "Sports and Recreations"=>{"Sports and Recreations"=>1}, "Psychology"=>{"Psychology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>11}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>2}}, "reader_count_by_country"=>{"Brazil"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/780220"], "description"=>"<p><b>A.</b> Dose dependent effects of METH on cell viability in human at 24 hr. <b>B.</b> Cell viability assay of human astrocytes treated with 20 µM METH in presence or absence of cytochalasin B (10 µM) or ALC (100 µM) for 72 hr and compared with untreated cells. Statistically significant (n = 5), **p<0.01 compared with controls in <b>A</b> and <b>B</b> and <sup>#</sup>p<0.05 with 20 µM METH or 10 µM cytochalasin B in <b>B</b>.</p>", "links"=>[], "tags"=>["glucose", "deprivation"], "article_id"=>450593, "categories"=>["Neuroscience", "Biochemistry", "Pharmacology", "Physiology", "Cell Biology"], "users"=>["P. M. Abdul Muneer", "Saleena Alikunju", "Adam M. Szlachetka", "James Haorah"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0019258.g005", "stats"=>{"downloads"=>1, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_METH_induced_glucose_deprivation_cause_cell_death_in_human_astrocytes_/450593", "title"=>"METH-induced glucose deprivation cause cell death in human astrocytes:", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 18:53:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/779972"], "description"=>"<p>Immunocytochemistry of GLUT3 (red) merged with NF (green) and DAPI (blue) in control (<b>A–B</b>), 20 µM METH (<b>C–D</b>), and 100 µM METH+100 µM ALC (<b>E–F</b>). Rabbit anti-GLUT3 and mouse anti-NF were used as primary antibodies for overnight at 4°C. Anti-rabbit-IgG Alexa Fluor 594 for GLUT3 and anti-mouse-IgG Alexa Fluor 488 for NF were used as secondary antibodies. Scale bar indicates 10 µm in all panels.</p>", "links"=>[], "tags"=>["meth", "glut3"], "article_id"=>450338, "categories"=>["Neuroscience", "Biochemistry", "Pharmacology", "Physiology", "Cell Biology"], "users"=>["P. M. Abdul Muneer", "Saleena Alikunju", "Adam M. Szlachetka", "James Haorah"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0019258.g003", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_METH_on_GLUT3_expression_in_human_neurons_/450338", "title"=>"Effects of METH on GLUT3 expression in human neurons:", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 18:51:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/779811"], "description"=>"<p><b>A.</b> Dose dependent effects of METH on D-(2-<sup>3</sup>H)-glucose uptake by human neurons for 24 hr. <b>B.</b> Effects of GLUT inhibitor cytochalasin B (10 µM) and ALC (100 µM) on glucose uptake by neurons following 20 µM and 100 µM of METH for 24 hr. <b>C.</b> Effect of 20 µM METH on D-(2-<sup>3</sup>H)-glucose uptake in human neurons at 24, 48 and 72 hr exposure periods and compared with respective untreated control cells. Statistically significant, *p<0.05, **p<0.01 compared with controls (n = 5 in <b>A</b> and <b>B</b>, n = 3 in <b>C</b>); <sup>##</sup>p<0.01 with 100 µM of METH (in <b>B</b>, n = 5).</p>", "links"=>[], "tags"=>["regulates", "glucose", "uptake"], "article_id"=>450180, "categories"=>["Neuroscience", "Biochemistry", "Pharmacology", "Physiology", "Cell Biology"], "users"=>["P. M. Abdul Muneer", "Saleena Alikunju", "Adam M. Szlachetka", "James Haorah"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0019258.g002", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_METH_down_regulates_glucose_uptake_in_human_neurons_/450180", "title"=>"METH down regulates glucose uptake in human neurons:", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 18:50:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/780810"], "description"=>"<p>Primary human neurons and astrocytes cultured in 96 well plates (20000 cells/well) in normal (+ glucose) or glucose-free (- glucose) media were exposed to 100 µM METH for 48 hr, and were analyzed for cell viability and ATP production. Viability of cells in glucose-deprived culture supplemented with pyruvate (PV)/palmitate (PA) in the presence or absence of ALC (100 µM) in (<b>A</b>) neurons and (<b>B</b>) astrocyte. Production of ATP in glucose-deprived culture with PV/PA in the presence or absence of ALC, (<b>C</b>) in neurons and (<b>D</b>) in astrocytes. Untreated (+) glucose is a positive control and untreated (-) glucose is a negative control. Results are expressed as mean values (± SEM; n = 3 in <b>A</b> and <b>B</b>; n = 5 in <b>C</b> and <b>D</b>). Statistically significant *p<0.05 and **p<0.01 compared with respective conditions (adjacent bars) in <b>A</b> and <b>B</b>; ***p<0.001 with compared with (-) glucose in <b>C</b> and <b>D</b>; <sup>#</sup>p<0.05 and <sup>##</sup>p<0.01 compared with (-) glucose+METH in <b>A</b> and B, and <sup>###</sup>p<0.001 with compared with (-) glucose+METH condition in <b>C</b> and <b>D</b>.</p>", "links"=>[], "tags"=>["neurons", "astrocytes", "glucose", "deprivation", "meth"], "article_id"=>451175, "categories"=>["Neuroscience", "Biochemistry", "Pharmacology", "Physiology", "Cell Biology"], "users"=>["P. M. Abdul Muneer", "Saleena Alikunju", "Adam M. Szlachetka", "James Haorah"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0019258.g009", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Utilization_of_pyruvate_palmitate_by_neurons_and_astrocytes_during_glucose_deprivation_and_METH_insult_/451175", "title"=>"Utilization of pyruvate/palmitate by neurons and astrocytes during glucose deprivation and METH insult:", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 18:56:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/780329"], "description"=>"<p><b>A.</b> Dose dependent effects of METH on D-(2-<sup>3</sup>H)-glucose uptake by human astrocytes for 24 hr. <b>B.</b> Effects of GLUT inhibitor cytochalasin B (10 µM) and ALC (100 µM) on glucose uptake by astrocytes following 20 µM and 200 µM of METH for 24 hr treatment. Statistically significant (n = 5), *p<0.05, **p<0.01 compared with controls in <b>A</b> and <b>B</b> and <sup>#</sup>P<0.05, <sup>##</sup>p<0.01 with 200 µM METH in B (third bar).</p>", "links"=>[], "tags"=>["meth", "glucose", "uptake"], "article_id"=>450696, "categories"=>["Neuroscience", "Biochemistry", "Pharmacology", "Physiology", "Cell Biology"], "users"=>["P. M. Abdul Muneer", "Saleena Alikunju", "Adam M. Szlachetka", "James Haorah"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0019258.g006", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Dual_effects_of_METH_on_glucose_uptake_in_astrocytes_/450696", "title"=>"Dual effects of METH on glucose uptake in astrocytes:", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 18:53:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/780677"], "description"=>"<p><b>A:</b> Effects of METH on 45 kDa GLUT1 protein levels in human astrocytes. The effects of cytochalasin B and ALC on GLUT1 expression also showed in the band pattern. <b>B.</b> Results are expressed as ratio of GLUT1 to that of α-actin bands, and presented as the mean values (± SEM; n = 5). (Statistically significant, *p<0.05 **p<0.01 compared with controls).</p>", "links"=>[], "tags"=>["blot", "glut1", "meth", "treated"], "article_id"=>451047, "categories"=>["Neuroscience", "Biochemistry", "Pharmacology", "Physiology", "Cell Biology"], "users"=>["P. M. Abdul Muneer", "Saleena Alikunju", "Adam M. Szlachetka", "James Haorah"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0019258.g008", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Western_blot_analysis_of_GLUT1_in_METH_treated_human_astrocytes_/451047", "title"=>"Western blot analysis of GLUT1 in METH treated human astrocytes:", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 18:55:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/780117"], "description"=>"<p><b>A-B:</b> Effects of METH on GLUT3 (45 kDa) protein levels in human neurons. Bar graph shows the results, which are expressed as ratio of GLUT3 to that of α-actin bands, and presented as the mean values (± SEM; n = 5). (Statistically significant, **p<0.01 compared with controls).</p>", "links"=>[], "tags"=>["blot", "glut3", "meth", "treated"], "article_id"=>450484, "categories"=>["Neuroscience", "Biochemistry", "Pharmacology", "Physiology", "Cell Biology"], "users"=>["P. M. Abdul Muneer", "Saleena Alikunju", "Adam M. Szlachetka", "James Haorah"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0019258.g004", "stats"=>{"downloads"=>3, "page_views"=>51, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Western_blot_analysis_for_GLUT3_expression_in_METH_treated_human_neurons_/450484", "title"=>"Western blot analysis for GLUT3 expression in METH treated human neurons.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 18:52:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/779673"], "description"=>"<p><b>A.</b> Dose dependent effects of METH on cell viability in human neurons at 24 hr. <b>B.</b> Cell viability assay of human neurons treated with 20 µM METH in presence or absence of cytochalasin B (10 µM) or ALC (100 µM) for 72 hr. Statistically significant (n = 5), **p<0.01 compared with controls in <b>A</b> and <b>B</b>; <sup>#</sup>P<0.05 with 20 µM METH in <b>B</b>; and <sup>@</sup>p<0.05 with 10 µM cytochalasin B in <b>B</b>.</p>", "links"=>[], "tags"=>["meth-induced", "glucose", "deprivation", "neuronal"], "article_id"=>450037, "categories"=>["Neuroscience", "Biochemistry", "Pharmacology", "Physiology", "Cell Biology"], "users"=>["P. M. Abdul Muneer", "Saleena Alikunju", "Adam M. Szlachetka", "James Haorah"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0019258.g001", "stats"=>{"downloads"=>3, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_METH_induced_glucose_deprivation_on_neuronal_viability_/450037", "title"=>"Effect of METH-induced glucose deprivation on neuronal viability:", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 18:50:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/780506"], "description"=>"<p>A-H: Immunocytochemistry of GLUT1 (red) merged with GFAP (green) and DAPI (blue) in human astrocytes. The expression of GLUT1 is shown in control (<b>A–B</b>), 20 µM METH (<b>C–D</b>), 200 µM METH (<b>E–F</b>) and 200 µM METH+100 µM ALC (<b>G–H</b>). Mouse anti-GLUT1 and rabbit anti-GFAP were used as primary antibodies for overnight at 4°C. Anti-mouse-IgG Alexa Fluor 594 for GLUT1 and anti-rabbit-IgG Alexa Fluor 488 for GFAP were used as the secondary antibodies. Scale bar indicates 10 µm in all panels.</p>", "links"=>[], "tags"=>["glut1", "meth", "treated"], "article_id"=>450877, "categories"=>["Neuroscience", "Biochemistry", "Pharmacology", "Physiology", "Cell Biology"], "users"=>["P. M. Abdul Muneer", "Saleena Alikunju", "Adam M. Szlachetka", "James Haorah"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0019258.g007", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_GLUT1_in_METH_treated_human_astrocytes_/450877", "title"=>"Expression of GLUT1 in METH treated human astrocytes:", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 18:54:51"}

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