Depressive Behavior and Monoamine Contents in Brain Structures of Rats During Chronic Overcrowding.

Effects of chronic overcrowding on the development of depressive-like behavior and changes in monoamine contents in the brain structures involved in the development of depression were studied in rats. It was shown that overcrowding increased grooming duration and did not change the number of crossed squares and postures in the open-field test. In the forced swimming test, overcrowding increased immobility time and deceased the duration of the first episode of active swimming, which attested to depressive-like behavior. Overcrowding reduced the content of dopamine in the striatum, its metabolites (homovanilic and dioxyphenylacetic acids) and dopamine metabolism rate in the hypothalamus, and increased the concentrations of norepinephrine, homovanilic acid, and dioxyphenylacetic acid in the olfactory bulb and homovanilic acid in the prefrontal cortex. No changes were found in the nucleus accumbens. Serotonin content did not change in all analyzed structures. It was hypothesized that the observed changes in the content of monoamines and their metabolites in certain brain structures could underlie the depressive-like behavior induced by overcrowding in rats.

Electrophysiological correlations of morphological restructuring in experimental local ischemia of different severity in the rat sensorimotor cortex.

Local cerebrovascular disorders were modeled by reversible photochemical clotting of hemispheric cortical vessels. Mild ischemia led to reversible edema in the surface layers of the cortex: cytotoxic edema of the neuropile, primarily of the distal dendrites. This status led to an increase in the lower delta rhythm frequency band power. After administration of systemic anesthetic, delta rhythm appeared sooner in the ischemic foci than in intact cortical areas. More severe ischemia led to the appearance of dark and pyknotic neurons and reduction of oscillation power in all EEG spectrum bands. Restructuring of primarily dendrites caused by local moderate ischemia of the surface cortical layers at the early stage of neurodegenerative processes stimulated the inhibitory recovery processes.

Immunological parameters of the blood and monoamine content in the brain of rats during long-term overcrowding.

Blood immunological parameters (cytokine profile and interferon status) and the level of monoamines and their metabolites in various brain structures (amygdala, hippocampus, septum, and hypothalamus) were studied in rats kept under standard conditions or in overpopulated cages. Long-term overcrowding was associated with reduced expression of IL-4 gene, increased transcription of IL-17, and decreased production of IFN-γ, which attested to impaired humoral and cell-mediated immunity and disturbances in IFN-γ synthesis at the post-transcriptional level. Under these conditions, the levels of norepinephrine and dopamine decreased in the septum, but increased in the hypothalamus. The amount of dopamine metabolite dihydroxyphenylacetic acid decreased in both these structures, and the index of dopamine metabolism (dihydroxyphenylacetic acid/dopamine ratio, DOPAC/dopamine) decreased only in the hypothalamus. Overcrowding was not followed by changes in the parameters of noradrenergic and dopaminergic systems in the amygdala and hippocampus and serotoninergic system in all study structures.

Anxiety level and body weight changes in rats living in overpopulated cages.

Behavioral indicators of anxiety and body weight dynamics were compared in rats kept under standard conditions (4-5 animals per cage) and in overpopulated cages (17 rats per cage). The behavior of rats exposed to overcrowding for a short and long period was evaluated in the open field, light-darkness, and elevated plus-maze tests. The anxiety parameters of animals increased only in the light-darkness test during the acute period of overcrowding and in all tests during chronic overcrowding. Behavioral tests had a negative impact on body weight gain in controls and rats living in overpopulated cages. If the behavioral tests were carried out at the beginning of the experiment, body weight ceased to increase in animals exposed to overcrowding and continued to increase in the controls. Overcrowding without behavioral tests had no effects on the body weight dynamics. The model of chronic (but not acute) overcrowding may be used for evaluation of anxiolytic effects of drugs.

[Effects of human cultural neuronal and mesenchymal stem cells on the rat learning and brain state after acute hypoxia].

The aim of the study was to compare the effects of neurotransplantation of cultural neural stem cells (NSC) and mesenchymal stem cells (MSC) on the rat behaviour and brain state after acute hypoxia. It was shown that development of two-way avoidance defensive conditioning in a shuttle box improved in rats-recipients with NSC, but not MSC as compared to control. Both the transplants of NSC and transplants of MSC exert neuroprotective influence on the rat brain. NSC both in vitro (before transplantation) and in vivo (on day 27 after transplantation) gave rise to all neural cell types: stem/progenitor cells, precursors of neurons and glia, neurons and glial cells. MSC population in vitro and in vivo (on day 10 after transplantation) consisted of fibroblast-like cells which were eliminated by day 20 after transplantation and were surrounded by reactive glia. We suggest that effects of NSC may be connected with their good survival and potential to differentiate into neurons and with trophic influence on the brain of recipient, whereas MSC only have possible positive trophic effect at early stages after transplantation.

[Effects of human and rat interferons-alpha on the behavior of rats of different ages. Comparative study of the homology of amino acid sequences].

Effects of chronic intranasal administration of human and rat interferons alpha on feeding and defensive behavior of rats were studied. Natural leukocyte human interferon "Lokferon" (a mixture of alpha interferon subtypes) and recombinant rat interferon alpha of the first subtype were used in the dose of 350 ME per rat daily. In addition, using the databases NCBI and EBI, we quantitatively estimated homology of amino-acid sequences between different subtypes of human and rat interferons. Both human (mostly in young rats) and rat interferons (mostly in old rats) increased rat feeding behavior after food conditioning to an audio tone. In old (but not in young) rats, both human and rat interferons worsened the ability of time interval assessment. In young (but not old) rats, both interferon kinds improved avoidance conditioning. The degree of homology between different human and rat interferons varied from 72% to 77%. Thus, generally, the effects of rat and human alpha interferons (350 ME) on rat conditioning were similar. This may be due to high degree of homology of amino-acid sequences between the two interferons.

[Dose-dependent effects of neuroimmunomodulator interferon alpha on behavior of humans and animals].

The review analyses the literature on polyfunctional activity of the cytokine interferon-alpha (IA) which has neuroimmunomodulatory properties and is used for treatment of viral and oncologic diseases. The major intention is devoted to action of small and high doses of IA on different forms of animals and human behavior. We suggest that chronic treatment with small IA doses is more effective than high dose therapy.

[The role of interferon-alpha in regulation of nervous system functions].

The review analyses contemporary data on the role of the interferon-alpha in the central nervous systems. Interferon-alpha is one of the key polyfunctional cytokines providing integrative activity of the neuro-immuno-endocrine complex. The emphasis is made on the molecular mechanisms of anti-viral, anti-proliferative and neuromodulating actions of the interferon-alpha in the brain. Mechanisms of its involvement in regulation of pain, sleep, body temperature, circadian rhythms, food consumption etc. are considered. Based on the literature and our data we hypothesized a dose-dependent action of exogenous interferon-alpha on the nervous system. We suggest that optimal schemes of chronic application of small interferon-alpha doses can be more expedient for treatment of viral or oncologic diseases than large doses causing neuropsychiatric disorders.

[Effect of small doses of interferon-alpha on food conditioning in young and ageing rats].

Low doses (10 or 350 ME) of human interferon-alpha (HIA) were intranasally applied to young (3-4 months) and ageing (12-15 months) Wistar rats during food conditioning. In control groups, development of the conditioned reflex to acoustic stimulus (tone) did not differ significantly in young and ageing rats in the course of chronic applications of the HIA. However, the control ageing rats were better than young rats in time-interval conditioning. Small doses of HIA do not cause anorexia in rats whereas large doses do so. Tone-conditioning did not change in rats of both ages when they were treated with 10 ME of the HIA; moreover, 350 ME increased food motivation, especially in young rats. Time-interval conditioning in aging rats was descended by both doses to the level of young rats, whereas in young rats it did not change at all. We suggest that these differences between ages may by accounted for be different affinity and concentration of micro-opiod receptors (which are the targets for the HIA) in the brain structures responsible for food behaviour, and for counting time intervals.

[Influence of small doses human interferon-alpha intranasal injection on behavior of rats of different age].

Behavior of young (3-4 month old) and ageing (12-15 month old) rats was studied during chronic intranasal application of low doses (10 ME or 350 ME) of human interferon-alpha (HIA). In ageing rats HIA did not affect dynamics (days 0th, 8th and 16th) of (a) locomotive and (b) investigative activity in the "open field" test and in two-side defensive conditioning, and (c) decreased anxiety ("open field", "light-darkness" test). In young rats HIA (a) increased locomotive activity by 16th day (it decreased in control), (b) investigative activity did not change (in control it decreased by 8th day; "open field" test), (c) anxiety decreased in the "open field" and increased in "light-darkness" tests, (d) development of conditioned reflex improved (during 2nd learning session in 5 days after the first one). Thus, small doses of HIA differently affected behavior of rats depending on the age and experimental situation. However, both HIA doses changed rats' behavior in the same direction. We suggest that chronic low doses of HIA can regulate different aspects of behavior, but not suppress activity as it is commonly thought. This regulation can be performed via modulation of neuro-immuno-endocrine complex.