PubMed · 6923913
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M M Stevens. 1982. Post concussion syndrome.. https://doi.org/10.1097/01376517-198210000-00006
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The current study used the passive avoidance test to examine whether heat shock pretreatment has an effect on the memory impairment induced by scopolamine. Heat shock protein (HSP) 72 overexpression was detected in different brain structures in rats 16 h after heat shock treatment, but not in rats receiving no heat shock or 48 h after heat shock treatment. The step-through latency of either pre- or post-training administration of scopolamine in rats 16 h after heat shock treatment was significantly higher than those of the rats receiving no heat shock or 48 h after heat shock treatment. However, rats, 16 h after heat shock treatment and having been given scopolamine, performed no better than rats treated only with scopolamine. Hence, the present results indicate that heat shock has a protective, but not therapeutic, effect on the memory impairment induced by scopolamine by overexpression of HSP72 in rat brain.
To discover new cognition enhancers, a set of virtually designed synthesizable compounds from different chemical series was investigated using two computer-aided approaches. One of the approaches is prediction of biological activity spectra for substances (PASS) and the second is prediction of toxicity, mutagenicity, and carcinogenicity (DEREK). To increase the probability of finding new chemical entities, we investigated a heterogeneous set of highly diverse chemicals including different types of heterocycles: five-membered (thiophenes, thiazoles, imidazoles, oxazoles, pyrroles), six-membered (pyridines, pyrimidines), seven-membered (diazepines, triazepines), fused five+six-membered heterocycles (indoles, benzothiazoles, purines, indolizines, neutral, mesoionic, and cationic azolopyridines). A database including 5494 structures of compounds was created. On the basis of the PASS and DEREK prediction results, eight compounds with the highest probability of cognition-enhancing effect were selected. The cognition-enhancing activity testing showed that all of the selected compounds had a pronounced antiamnesic effect and were found to reduce significantly scopolamine-induced amnesia of passive avoidance reflex (PAR). The action of compounds at doses of 1 and 10 mg/kg caused a statistically significant increase in latent time of reflex and in the number of animals, which did not enter the dark chamber when testing the PAR. Therefore, on the basis of computer prediction, new cognition-enhancing agents were discovered within the chemical series, in which this activity was not known previously.
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