The anthraquinone derivative Emodin ameliorates neurobehavioral deficits of a rodent model for schizophrenia.
Abnormality in cytokine signaling is implicated in the neuropathology of schizophrenia. Previously, we established an animal model for schizophrenia by administering epidermal growth factor (EGF) to neonatal rats. Here we investigated effects of the anthraquinone derivatives emodin (3-methyl-1,6,8-trihydroxyanthraquinone) and sennoside (bis-[D: -glucopyranosyl-oxy]-tetrahydro-4,4'-dihydroxy-dioxo[bianthracene]-2,2'-dicarboxylic acid) on behaviors of this model and EGF signaling. Subchronic oral administration of emodin (50 mg/kg) suppressed acoustic startle responses and abolished prepulse inhibition (PPI) deficits in this rodent model. ANCOVA revealed that emodin had distinct effects on PPI and startle responses. In contrast, sennoside (50 mg/kg) had no effects. Emodin attenuated weight gain initially during treatment but had no apparent effect on weight gain and locomotor activity thereafter. Application of emodin to neocortical cultures attenuated the phosphorylation of ErbB1 and ErbB2. We conclude that emodin can both attenuate EGF receptor signaling and ameliorate behavioral deficits. Therefore, emodin might be a novel class of a pro-drug for anti-psychotic medication.
Mizuno
M
M
Center for Transdisciplinary Research, Niigata University, Niigata, Japan.
Kawamura
H
H
Takei
N
N
Nawa
H
H
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D015153:Blotting, Western; D002400:Cathartics / Q000494:pharmacology; D004195:Disease Models, Animal; D004642:Emodin / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000633:toxicity; D009433:Neural Inhibition / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects; D012559:Schizophrenia / Q000139:chemically induced / Q000188:drug therapy*; D012676:Senna Extract; D000081226:Sennosides
D000880:Anthraquinones; D014150:Antipsychotic Agents; D002400:Cathartics; D047428:Protein Kinase Inhibitors; D000081226:Sennosides; D004815:Epidermal Growth Factor; D012676:Senna Extract; D004642:Emodin