title: Melatonin reverses the decreases in hippocampal protein serine/threonine kinases observed in an animal model of autism.
abstract: Lower global cognitive function scores are a common symptom of autism spectrum disorders (ASDs). This study investigates the effects of melatonin on hippocampal serine/threonine kinase signaling in an experimental ASD model. We found that chronic melatonin (1.0 or 5.0 mg/kg/day, 28 days) treatment significantly rescued valproic acid (VPA, 600 mg/kg)-induced decreases in CaMKII (Thr286), NMDAR1 (Ser896), and PKA (Thr197) phosphorylation in the hippocampus without affecting total protein levels. Compared with control rats, the immunostaining of pyramidal neurons in the hippocampus revealed a decrease in immunolabeling intensity for phospho-CaMKII (Thr286) in the hippocampus of VPA-treated rats, which was ameliorated by chronic melatonin treatment. Consistent with the elevation of CaMKII/PKA/PKC phosphorylation observed in melatonin-treated rat, long-term potentiation (LTP) was enhanced after chronic melatonin (5.0 mg/kg) treatment, as reflected by extracellular field potential slopes that increased from 56 to 60 min (133.4 ± 3.9% of the baseline, P < 0.01 versus VPA-treated rats) following high-frequency stimulation (HFS) in hippocampal slices. Accordingly, melatonin treatment also significantly improved social behavioral deficits at postnatal day 50 in VPA-treated rats. Taken together, the increased phosphorylation of CaMKII/PKA/PKC signaling might contribute to the beneficial effects of melatonin on autism symptoms.
authors: Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, Zhejiang University, Hangzhou, China.
authors: Yun
authors: Y
authors: Tian
authors: Yasushi
authors: Y
authors: Yabuki
authors: Shigeki
authors: S
authors: Moriguchi
authors: Kohji
authors: K
authors: Fukunaga
authors: Pei-Jiang
authors: PJ
authors: Mao
authors: Ling-Juan
authors: LJ
authors: Hong
authors: Ying-Mei
authors: YM
authors: Lu
authors: Rui
authors: R
authors: Wang
authors: Muhammad Masood
authors: MM
authors: Ahmed
authors: Mei-Hua
authors: MH
authors: Liao
authors: Ji-Yun
authors: JY
authors: Huang
authors: Rui-Ting
authors: RT
authors: Zhang
authors: Tian-Yi
authors: TY
authors: Zhou
authors: Sen
authors: S
authors: Long
authors: Feng
authors: F
authors: Han
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001321:Autistic Disorder; D001522:Behavior, Animal / Q000187:drug effects*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology*; D007150:Immunohistochemistry; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D014635:Valproic Acid; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D008550:Melatonin
keywords: CaMKII; autism; hippocampus; melatonin; phosphorylation; valproic acid