LIM-kinase 1 effects on memory abilities and male courtship song in Drosophila depend on the neuronal type.

The signal pathway of actin remodeling, including LIM-kinase 1 (LIMK1) and its substrate cofilin, regulates multiple processes in neurons of vertebrates and invertebrates. Drosophila melanogaster is widely used as a model object for studying mechanisms of memory formation, storage, retrieval and forgetting. Previously, active forgetting in Drosophila was investigated in the standard Pavlovian olfactory conditioning paradigm. The role of specific dopaminergic neurons (DAN) and components of the actin remodeling pathway in different forms of forgetting was shown. In our research, we investigated the role of LIMK1 in Drosophila memory and forgetting in the conditioned courtship suppression paradigm (CCSP). In the Drosophila brain, LIMK1 and p-cofilin levels appeared to be low in specific neuropil structures, including the mushroom body (MB) lobes and the central complex. At the same time, LIMK1 was observed in cell bodies, such as DAN clusters regulating memory formation in CCSP. We applied GAL4 × UAS binary system to induce limk1 RNA interference in different types of neurons. The hybrid strain with limk1 interference in MB lobes and glia showed an increase in 3-h short-term memory (STM), without significant effects on long-term memory. limk1 interference in cholinergic neurons (CHN) impaired STM, while its interference in DAN and serotoninergic neurons (SRN) also dramatically impaired the flies' learning ability. By contrast, limk1 interference in fruitless neurons (FRN) resulted in increased 15-60 min STM, indicating a possible LIMK1 role in active forgetting. Males with limk1 interference in CHN and FRN also showed the opposite trends of courtship song parameters changes. Thus, LIMK1 effects on the Drosophila male memory and courtship song appeared to depend on the neuronal type or brain structure.

[Effect of tryptophan and kynurenine on the cellular proliferation in the organotypic tissue culture of brain cortex in young and old rats.]

Metabolic disorders of L-kinurenin, which is an intermediate product of the breakdown of genetically encoded amino acid L-tryptophan, is one of the links in the development of a number of neuropathological processes. The influence of tryptophan and kynurenine on cell proliferation in organotypic tissue culture of the cerebral cortex in young and old rats was studied. Tryptophan in effective concentration (0,5 ng/ml) inhibited cellular proliferation of the cerebral cortex of young and old rats by 35 and 18%, respectively. However, under the action of kinurenin (1 ng/ml), stimulation of cell proliferation occurred, and more pronounced in the explants of the cerebral cortex of old rats-by 22% compared to the control. The data obtained about the ability of kynurenine to stimulate cellular proliferation in the cerebral cortex of old animals has the potential to create new drugs of nootropic drugs for diseases of the nervous system associated with age.

[Effect of genetically coded amino acids and their precursors carboxylic acids on the cellular proliferation in the organotypic culture of spleen in young and old rats].

Effect of carboxylic acids - structurally related to amino acids, on the proliferation activity of the cells in organotypic cultures of rat spleen was first studied. It was found that almost all aliphatic carboxylic acids have stimulating effects on proliferative activity of cells in young and old rats. In contrast only 3 from 14 active amino acids in young rats were able stimulate proliferation, but 11 amino acids inhibited it. In the old rats a number of the active amino acids was decreased until 4, an inhibiting effect was observed in 3 of them. Thus, the carboxylic acids are able to stimulate the regeneration processes in the immune tissue both in the young and old organisms. This fact can be a base for the research of new medical substances for the stimulation of the immunogenesis by the aging.