RESUMEN
Molecular mechanisms of the synapse and dendrite maintenance and their disturbance in psychiatric and neurodegenerative diseases (ND) are intensively studied in searching for target genes of therapeutic actions. It is suggested that glia, alongside with well-studied pre- and postsynaptic neurons, is the third, poorly studied partner in synaptic transmission (the tripartite synapse) that is involved in the positive feedback between the first two partners. This bidirectional coupling between presynaptic neurons and their postsynaptic targets involve neurotrophins (NTF), such as glial cell-derived neurotrophic factor (GDNF) that is produced LIM kinase 1 (LIMK1, the key enzyme of actin remodeling). The cytoplasmic domain of neuregulins interacts with LIMK1. Since neurons and axons that do not receive a sufficient NTF amount are at risk of degeneration and synapse elimination, GDNF seems to be the best studied factor of the ND therapy. The delivery of GDNF stem cells to the neurodegeneration locus is very efficient. There has been proposed a new approach based on use of Drosophila heat shock (hs) promoter. This promoter responds to the mammalian body temperature as to the shock factor resulting in the constant expression of the GDNF gene. The Drosophila models allow studying any given component of the bidirectional communication between pre- and postsynaptic neurons in development of the main diagnostic ND symptom, such as defective memory resulted from synaptic atrophy. In the present study we used the Drosophila stocks imitating different disturbances of the nervous system: Canton-S (wild type), GDNF (transgenic flies that carry human glial-cell-line derived nerve factor (GDNF) gene under hs promoter), l(1)ts403 with dusturbance of HSPs mRNA extranuclear transport, a defect of intracellular stress report, and agn(ts3) mutation in LIMK1 gene. We have revealed functional connections at the behavioral level (learning/memory) depending on the GDNF and LIMK1 brain expression and HSPs transduction that might provide targets for complex approaches for the ND treatment.