RESUMO
Humulus japonicus (HJ) is a traditional herbal medicine that exhibits antiinflammatory, antimicrobial and antitumor effects that is used for the treatment of hypertension, pulmonary disease and leprosy. Recently, it has also been reported that HJ demonstrates neuroprotective properties in animal models of neurodegenerative diseases. The current study hypothesised that the administration of HJ would exhibit therapeutic effects in autism spectrum disorder (ASD), a neurodevelopmental disorder with lifelong consequences. The BTBR T+ Itpr3tf/J mouse model of ASD was used to investigate the antiautistic like behavioural effects of HJ. Chronic oral administration of the ethanolic extract of HJ significantly increased social interaction, attenuated repetitive grooming behaviour and improved novelobject recognition in BTBR mice. Antiinflammatory effects of HJ in the brain were analysed using immunohistochemistry and reversetranscription quantitative PCR analysis. Microglia activation was markedly decreased in the striatum and hippocampus, and proinflammatory cytokines, including CC Motif Chemokine Ligand 2, interleukin (IL)1ß and IL6, were significantly reduced in the hippocampus following HJ treatment. Moreover, HJ treatment normalised the phosphorylation levels of: NmethylDaspartate receptor subtype 2B and calcium/calmodulindependent protein kinase type II subunit α in the hippocampus of BTBR mice. The results of the present study demonstrated that the administration of HJ may have beneficial potential for ameliorating behavioural deficits and neuroinflammation in ASD.
Assuntos
Transtorno Autístico/tratamento farmacológico , Humulus/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Transtorno do Espectro Autista/tratamento farmacológico , Transtorno Autístico/genética , Comportamento Animal/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Hipocampo/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Fosforilação/efeitos dos fármacosRESUMO
Dapsone (4,4'-diaminodiphenyl sulfone; DDS), an established anti-leprosy drug, showed anticonvulsive effects in the amygdaloid kindling model of epilepsy. Single doses of the drug in rats (6.25-12.5 mg/kg, i.p.) suppressed the kindled seizures in a dose-dependent manner without overt behavioral toxicity. With repeated oral administration in cats, relatively higher initial doses (13-23 mg/kg) were required to obtain seizure suppression, and neurotoxic signs occurred within a few days with serum drug levels of approximately 20 micrograms/ml. Although dapsone showed anticonvulsive effects in both animal species, the effective serum levels overlapped the toxic levels reported in the clinical treatment of leprosy. In the majority of the cats, however, seizure suppression was maintained even after the discontinuation of dapsone with lower serum levels than those observed at the beginning of the seizure suppression. Therefore, dapsone would be useful as an antiepileptic drug only when long-term anticonvulsive efficacy is demonstrated using smaller doses comparable to those used in the treatment of leprosy.
Assuntos
Tonsila do Cerebelo/efeitos dos fármacos , Anticonvulsivantes/uso terapêutico , Dapsona/uso terapêutico , Epilepsia/tratamento farmacológico , Excitação Neurológica/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Gatos , Dapsona/toxicidade , Avaliação Pré-Clínica de Medicamentos , Epilepsia/fisiopatologia , Feminino , Masculino , Estrutura Molecular , Ratos , Ratos Endogâmicos , Síndrome de Abstinência a Substâncias/fisiopatologiaRESUMO
A biting behavior in the Moroccan pond tortoise (Clemmys caspica leprósa) after apomorphine administration is described. The biting behavior was antagonized by the specific anti-dopaminergic drug haloperidol (10 mg/kg) and trifluperazine (15 mg/kg). The behavior was compared to similar behaviors in birds and mammals. The dopamine metabolites, homovanillic acid and 3,4-dihydroxyphenylacetic acid, were measured by a gas chromatographic method in the tortoise brain. From the effects on behavior and the changes in the level of these metabolites upon drug administration it was concluded that the dopamine system in the tortoise is qualitatively similar to that in birds and mammals but less sensitive to blockade.