RESUMO
Omega-3 polyunsaturated fatty acids (PUFA) are critical for optimal brain health and are involved in psychiatric and neurological ailments. Here, we report the effects of higher endogenous omega-3 PUFA on memory impairment in the hippocampus by studying mice with transgenic expression of the fat-1 gene that converts omega-6 to omega-3 PUFA. We performed Y-maze and passive avoidance tests to evaluate the memory function of fat-1 mice treated with scopolamine. Fat-1 mice showed induced alternation in the Y-maze test and increased latency in the passive avoidance test. The effects of scopolamine on hippocampal neurogenesis were confirmed by increases in the number of Ki-67- and DCX-positive cells in the fat-1 mice. Western blotting revealed increased brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element-binding protein levels, and lower scopolamine-induced apoptosis based on the cleaved-caspase 3 protein level in fat-1 mice. These findings suggest that higher endogenous omega-3 PUFA prevented granular cell loss, increased BDNF signaling, and decreased apoptosis signaling in scopolamine-treated fat-1 mice. These processes may underlie granular cell survival and suggest potential therapeutic targets for memory impairment.
Assuntos
Amnésia/metabolismo , Caderinas/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Hipocampo/efeitos dos fármacos , Memória/efeitos dos fármacos , Escopolamina/efeitos adversos , Acetilcolinesterase/metabolismo , Doença de Alzheimer/metabolismo , Amnésia/induzido quimicamente , Amnésia/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteína Duplacortina , Ácidos Graxos Ômega-3/administração & dosagem , Hipocampo/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurogênese/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/farmacologiaRESUMO
Temozolomide (TMZ) is an alkylating agent commonly used as a firstline treatment for highgrade glioblastoma. However, TMZ has short halflife and frequently induces tumor resistance, which can limit its therapeutic efficiency. In the present study, it was hypothesized that combined treatment with TMZ and acteoside has synergistic effects in glioblastoma therapy. Using cell viability and woundhealing assays, it was determined that this treatment regimen reduced cell viability and migration to a greater extent than either TMZ or acteoside alone. Following previous reports that TMZ affected autophagy in glioma cells, the present study examined the effects of TMZ + acteoside combination treatment on apoptosis and autophagy. The TMZ + acteoside combination treatment increased the cleavage of caspase3 and levels of Bcell lymphoma 2 (Bcl2)associated X protein and phosphorylated p53, and decreased the level of Bcl2. The combination treatment increased microtubuleassociated protein 1 light chain 3 and apoptosisrelated gene expression. It was also determined that TMZ + acteoside induced apoptosis and autophagy through the mitogenactivated protein kinase signaling pathway. These findings suggest that acteoside has beneficial effects on TMZbased glioblastoma therapy.
Assuntos
Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Glucosídeos/farmacologia , Fenóis/farmacologia , Temozolomida/farmacologia , Animais , Antineoplásicos Alquilantes/química , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioblastoma/genética , Glioblastoma/metabolismo , Glucosídeos/química , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fenóis/química , Ratos , Temozolomida/químicaRESUMO
Rotavirus group C is the major etiological agent associated with acute gastroenteritis in all human age groups. Here, we report the complete genome sequence of human group C rotavirus (GpC-RV) isolated in South Korea.