RESUMO
The effects of caspase inhibitors on different types of learning and memory were studied in adult rats on administration into the cerebral ventricles and application to the vermis of the cerebellum. The wide-spectrum caspase inhibitor z-VAD-fmk, given into the lateral ventricles of adult rats, facilitated the formation of long-term spatial memory in a water maze and increased the ability to rearrange the habit at the early stages of acquisition of this skill. Application of the specific caspase 3 inhibitor z-DEVD-CHO to the cerebellar vermis stimulated the extinction of an acoustic startle reaction but had no effect on its retention or reproduction. These results indicate that caspases may be involved in the mechanisms of learning and memory both via indirect influences on the linked processes of neurogenesis and apoptosis in the adult brain and by regulating synaptic efficiency.
Assuntos
Caspase 3/metabolismo , Inibidores de Caspase , Inibidores de Cisteína Proteinase/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Oligopeptídeos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Ventrículos Cerebrais/enzimologia , Masculino , Memória , Ratos , Ratos WistarRESUMO
Effects of caspase inhibitors injected intracerebroventricularly or applicated to cerebellar vermis of adult rats on different types of learning and memory were studied. Pancaspase inhibitor z-VAD-fmk introduced into lateral cerebral ventriculi enhanced elaboration of long-term spatial memory in Morris water maze and stimulated habit alteration at the early stage of its formation. Caspase-3 inhibitor z-DEVD-CHO applied to cerebellar vermis enhanced the elaboration of acoustic startle habituation but had no effect on its storage and retrieval. These results indicate caspase participation in mechanisms of learning and memory both through influence on coupled processes of neurogenesis-apoptosis and through modulation of synaptic efficiency.
Assuntos
Caspase 3/metabolismo , Inibidores de Caspase , Inibidores de Cisteína Proteinase/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Oligopeptídeos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Ventrículos Cerebrais/enzimologia , Masculino , Memória , Ratos , Ratos WistarRESUMO
We studied the effects of central administration of pancaspase inhibitor z-VAD-fmk and specific caspase 3 inhibitor z-DEVD-fmk on learning and memory in rats. The inhibitors selectively facilitated the formation of freezing behavior without modulating consolidation and retrieval of passive defense behavior in the model of conditioned freezing.
Assuntos
Clorometilcetonas de Aminoácidos/farmacologia , Comportamento Animal , Inibidores de Caspase , Inibidores de Cisteína Proteinase/farmacologia , Oligopeptídeos/farmacologia , Clorometilcetonas de Aminoácidos/administração & dosagem , Animais , Inibidores de Cisteína Proteinase/administração & dosagem , Masculino , Oligopeptídeos/administração & dosagem , Ratos , Ratos WistarRESUMO
CBA mice were given a single Desferal dose (50 mg/kg). The mice received 3H-Thymidine 1 hour before they were killed. They were killed 1, 2, 6, or 9 hours after Desferal. Radiometry, and autoradiography were used to determine the level of DNA synthesis. Desferal was found to stimulate splenic 3H-incorporation 3 hours after drug injection and to increase the DNA-synthesizing cell fraction. In contrast, the agent inhibited 3H-incorporation in the bone marrow and thymus 9 hours after injection. This suppressive affect was accompanied by a decrease in the DNA-synthesizing cell fraction in these organs. In the thymus, there was a significant increase in the DNA-synthesizing cell fraction among lymphoblasts 1 and 3 hours following the administration of Desferal.
Assuntos
Medula Óssea/efeitos dos fármacos , Desferroxamina/farmacologia , Baço/efeitos dos fármacos , Timo/efeitos dos fármacos , Animais , Autorradiografia , Medula Óssea/metabolismo , Células da Medula Óssea , Divisão Celular/efeitos dos fármacos , DNA/biossíntese , DNA/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos CBA , Baço/citologia , Baço/metabolismo , Timo/citologia , Timo/metabolismo , Fatores de TempoRESUMO
Human bone marrow cells were separated by centrifugation in percoll discontinuous density gradient with 1.020-1.080 g/ml densities. CFU-GM test and EPICS analysis were used to characterize cell compositions of the resultant fractions. The employed mode of separation permits obtaining cell fractions rich for monocytes, macrophages, T and B lymphocytes.