[Cross-Talk of the Glutamate and Leptin Receptor Pathways].

The hormone leptin is produced in adipocytes of white adipose tissue and crosses the blood-brain barrier. Leptin receptors are present in the brain regions that are involved in higher cognitive functions. In particular, leptin directly influences the glutamate receptor trafficking in CA3 → CA1 synapses to increase the phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) level, which is controlled by phosphoinositide 3-kinase (PI3K). It is well recognized that glutamate receptor trafficking involves at least some components of the insulin signaling cascade. However, the effects of leptin and insulin hormones differ at the cell and behavioral levels and often oppose each other. The domain organization of synaptic proteins was analyzed for CA1 field neurons. A molecular mechanism of leptin effects in the hippocampus was assumed to involve a cross-talk of the molecular pathways of the leptin receptors and NMDA-type glutamate receptors. Non-receptor protein kinases of the Src subfamily and, in particular, kinase Fyn are part of glutamate receptor macrocomplexes and are involved in regulating the efficiency of synaptic transmission. Fyn was assumed to utilize its SH2 domain to interact with leptin receptors directly or through other proteins and contribute to leptin signaling through the PI3K signaling pathway. The hypothesis explains experimental findings and sheds further light on the fine tuning of hormone-dependent modulation of hippocampal synaptic processes.

[Protein-Protein Interactions of Huntingtin in the Hippocampus].

Huntingtin (HTT) occurs in the neuronal cytoplasm and can interact with structural elements of synapses. Huntington's disease (HD) results from pathological expansion of a polyglutamine stretch in the HTT molecule, being probably associated with aberrant protein-protein interactions. The pathogenetic mechanism is still incompletely understood. Alterations of the synaptic structure and plasticity in the hippocampus are observed in early HD. The objective of the study was to theoretically evaluate the HTT contribution to changes in synaptic plasticity by integrating the available experimental data. HTT protein complexes are involved in maintaining the efficiency of synaptic transmission. A pathogenic HTT form (polyQ-HTT) probably disrupts the protein-protein interactions in distorts the dynamics of molecular processes in the synapsis. It was assumed that polyQ-HTT may compete with postsynaptic density proteins and proteins regulating cytoskeleton remodeling.

Amide of Lambertian Acid Suppresses Hyperactivation of Inotropic Glutamate Receptors, but not Synaptic Potentiation in Hippocampal Sections.

Amide of lambertian acid suppresses hyperactivation of inotropic glutamate receptors in hippocampal sections induced by a decrease in the level of magnesium ions (a selective blocker of glutamate NMDA receptors). Treatment of the sections with amide of lambertian acid in standard physiological saline does not prevent development of NMDA-dependent synaptic potentiation. Lambertian acid isolated from needles and turpentine of Siberian pine (Pinus sibirica R. Mayr), and its derivatives may become a source of substances with glutamatergic mechanism of action for treatment of cognitive and neurodegenerative disorders.

[MOBILITY OF AMPA SUBTYPE GLUTAMATE RECEPTOR AS A KEY FACTOR OF EXPRESSION AND MAINTENANCE OF SYNAPTIC POTENTIATION].

A time dynamic of LTP development in the first minutes after high frequency stimulation has been investigated by using a cell model of synaptic potentiation. An experimental assessment of dependence of potentiation and maintenance of a stable level of synaptic transmission in the CA1 area of mice hippocampus on the intracellular transport has been made with brefeldin A (the blocker of transport vesicle forming). The integrative activity of the systems, ensuring the delivery of glutamate receptors to the dendrite spines in amounts and in time intervals necessary for fast changing and long maintenance of transmission efficiency is discussing.

Substances in subthreshold concentrations under stress conditions can act as conditioned stimuli and trigger defense reactions.

The capacity of living systems to perceive low-intensity stimuli sometimes inducing protective reactions is still little studied. Incubation of neurons under conditions increasing the content of cAMP and Ca(2+) increases the amplitude of their responses to lidocaine (10(-3) M). After cell preconditioning with low concentrations of lidocaine (10(-15) M) under these conditions, the protective effects of "ineffective" concentrations were detected, because the response amplitude did not decrease. It was hypothesized that the basic amplitude responses retrieved by lidocaine in a concentration of 10(-3) M are memory traces about the effects of this compound in subthreshold concentrations.