anisomycin and cordycepin

The process of memory consolidation involves the synthesis of new proteins, and interfering with protein synthesis through anisomycin can impair memory. Memory deficits due to aging and sleep disorders may also result from a reduction in protein synthesis. Rescuing memory deficits caused by protein synthesis deficiency is therefore an important issue that needs to be addressed. Our study focused on the effects of cordycepin on fear memory deficits induced by anisomycin using contextual fear conditioning. We observed that cordycepin was able to attenuate these deficits and restore BDNF levels in the hippocampus. The behavioral effects of cordycepin were dependent on the BDNF/TrkB pathway, as demonstrated by the use of ANA-12. Cordycepin had no significant impact on locomotor activity, anxiety or fear memory. Our findings provide the first evidence that cordycepin can prevent anisomycin-induced memory deficits by regulating BDNF expression in the hippocampus.

Topics: Anisomycin; Brain-Derived Neurotrophic Factor; Fear; Hippocampus; Humans; Memory Disorders

The purpose of the experiments reported here is to provide evidence that motoneurons (MTNs) isolated from chick embryo spinal cords go through an active process of cell death when deprived of trophic support in vitro. In order to analyze and characterize this process, MTNs were isolated with a metrizamide gradient technique and cultured in the presence of saturating concentrations of soluble muscle extract. When muscle extract was washed off from the cultures, MTNs entered a process of cell death that could be blocked with inhibitors of mRNA and protein synthesis. Two other additional criteria were used to define this process as an active one. First, ultrastructural analysis of MTNs dying as a consequence of muscle extract deprivation showed that some, but not all, of the MTNs displayed clear signs of apoptotic cell death. Those included cytoplasm condensation, fragmentation of chromatin, and preservation of cytoplasmic organelles. Second, internucleosomal degradation of DNA was detected in MTNs deprived of muscle extract. When DNA was analyzed by Southern hybridization techniques using digoxigenin-labeled genomic probes, a clear ladder pattern could be identified on muscle extract-deprived MTNs. The degradation of DNA upon trophic deprivation could be prevented by cycloheximide (CHX). In an attempt to characterize further the process of active cell death in MTNs, we found a time point of commitment to cell death of approximately 10 hr by using three different approaches: muscle extract deprivation plus readdition of muscle extract, muscle extract deprivation plus addition of CHX, and muscle extract deprivation plus addition of actinomycin D. Moreover, we show that MTNs deprived of trophic support from muscle extract but maintained alive with CHX could not be rescued from cell death by reading muscle extract if CHX was washed off the cultures within the first 15 hr of muscle extract deprivation. However, muscle extract alone was able to rescue MTNs that had been kept alive with CHX for periods of time longer than 24 hr after muscle extract deprivation. From these results we postulate that the activation of the cell death program after trophic deprivation is transient.

Topics: Animals; Anisomycin; Apoptosis; Blotting, Southern; Camptothecin; Cell Communication; Cell Separation; Cell Survival; Centrifugation, Density Gradient; Chick Embryo; Chickens; Cycloheximide; Dactinomycin; Deoxyadenosines; DNA; Gene Expression; Immunohistochemistry; Metrizamide; Microscopy, Electron; Motor Neurons; Muscle Denervation; Muscles; Neurofilament Proteins; Puromycin; Spinal Cord