title: Temporal profiles of synaptic plasticity-related signals in adult mouse hippocampus with methotrexate treatment.
abstract: Methotrexate, which is used to treat many malignancies and autoimmune diseases, affects brain functions including hippocampal-dependent memory function. However, the precise mechanisms underlying methotrexate-induced hippocampal dysfunction are poorly understood. To evaluate temporal changes in synaptic plasticity-related signals, the expression and activity of N-methyl-D-aspartic acid receptor 1, calcium/calmodulin-dependent protein kinase II, extracellular signal-regulated kinase 1/2, cAMP responsive element-binding protein, glutamate receptor 1, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor were examined in the hippocampi of adult C57BL/6 mice after methotrexate (40 mg/kg) intraperitoneal injection. Western blot analysis showed biphasic changes in synaptic plasticity-related signals in adult hippocampi following methotrexate treatment. N-methyl-D-aspartic acid receptor 1, calcium/calmodulin-dependent protein kinase II, and glutamate receptor 1 were acutely activated during the early phase (1 day post-injection), while extracellular signal-regulated kinase 1/2 and cAMP responsive element-binding protein activation showed biphasic increases during the early (1 day post-injection) and late phases (7-14 days post-injection). Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression increased significantly during the late phase (7-14 days post-injection). Therefore, methotrexate treatment affects synaptic plasticity-related signals in the adult mouse hippocampus, suggesting that changes in synaptic plasticity-related signals may be associated with neuronal survival and plasticity-related cellular remodeling.
authors: Department of Veterinary Anatomy, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea.
authors: Miyoung
authors: M
authors: Yang
authors: Department of Veterinary Anatomy, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea.
authors: Juhwan
authors: J
authors: Kim
authors: Department of Veterinary Anatomy, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea.
authors: Sung-Ho
authors: SH
authors: Kim
authors: Department of Experimental Radiation, Research Center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), Busan 619-753, South Korea.
authors: Joong-Sun
authors: JS
authors: Kim
authors: Department of Veterinary Anatomy, College of Veterinary Medicine, Jeju National University, Jeju 690-756, South Korea.
authors: Taekyun
authors: T
authors: Shin
authors: Department of Veterinary Anatomy, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea.
authors: Changjong
authors: C
authors: Moon
keywords: hippocampus; methotrexate; neural regeneration; neurotrophic factor; synaptic plasticity-related signal
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