Effect of potentiated antiserum to brain-specific protein S100 in a concentration of 10 -'~176 prepared according to standard homeopathic procedures on integrative activity ot ~ rat brain was studied on models of conditioned avoidance reaction and self-stimulation of the lateral hypothalamus through chronically implanted electrodes. The antibodies reversibly inhibit memory processes during avoidance reaction. The incidence of the self-stimulation reaction increased after single administration of potentiated antibodies, while their administration for 5 days decreased the incidence of this reaction. Administration of water caused no such effects.
We studied the effect of morphine hydrochloride, brain-specific S100 protein, and antibodies to morphine, S100 protein, and opiate mu-receptors in ultralow doses on self-stimulation of the lateral hypothalamus in morphinized rats. This reaction in morphine-withdrawn rats underwent specific changes after single administration of test preparations. Repeated treatment with preparations in the same dose equalized emotional homeostasis. This effect was especially pronounced after treatment with antibodies to morphine, S100 protein, and opiate mu-receptors. Our findings should be taken into account in developing methods for non-narcotic substitutive therapy of patients with morphine dependence.
Sleep disorders, which are among the earliest and most sensitive non-motor manifestations of Parkinson's disease (PD), are not diagnosed in 40–50 % of patients and are not subject to the necessary correction. In this regard, the ineffectiveness of a late start of treatment, when more than 50 % of dopamine-producing neurons are already affected, dictates the need to search for and develop approaches to the prevention and slowdown of neurodegenerative pathology at the preclinical stages of its development using adequate experimental models. Taking into account the low bioavailability of dopamine (DA) and data on the advantages of the intranasal route of administration in comparison with oral and parenteral methods of drug delivery to the CNS, the aim of the work was to study the neurophysiological features of the wake-sleep cycle as early manifestations of nigrostriatal insufficiency and the effect of intranasal administration of DA on the quality of sleep during the formation of the preclinical stage of PD in rats. It was shown that under the conditions of modeling PD, the cyclic organization of sleep with a predominance of incomplete cycles against the background of hyperproduction of slow-wave sleep and REM phases are early manifestations of nigrostriatal insufficiency. Course administration of DA at a dose of 3 mg/kg is accompanied by the normalization of sleep quality in the form of reduction (by 76 %) in the number of incomplete cycles. The preventive orientation of the obtained effects may indicate a certain therapeutic potential of intranasal delivery of DA to the brain, aimed at slowing down the processes of neurodegeneration and possibly delaying its clinical manifestation
We studied the effect of potentiated antibodies to morphine (10(-100) wt %) on self-stimulation of the lateral hypothalamus and behavioral reactions reflecting the severity of withdrawal syndrome in rats with morphine dependence. Repeated treatment with potentiated antibodies to morphine increased the rate of self-stimulation, suppressed active avoidance response, promoted freezing behavior after acoustic stimulation, and decreased tail-flick latency in rats after morphine withdrawal. Distilled water did not produce these changes.
We studied the effects of morphine and its potentiated form on nociceptive thresholds in rats with the morphine withdrawal syndrome. Repeated combination (bipathic) treatment with morphine and its potentiated form increased nociceptive threshold and, therefore, activated the nociceptive system in the brain.
We compared the effects of neurotropic and neurospecific substances and their antibodies on conditioned activity of rats. Single treatment produced the positive effect on the latency and number of conditioned responses. Repeated treatment with test compounds in the same dose improved conditioned activity of animals.
The effect of homeopathically potentiated antibodies to mu-receptors (10(-100) wt %) on integrative activity of rat brain was studied using the models of self-stimulation of the lateral hypothalamus and convulsions produced by electric current. Electric current was delivered through electrodes implanted into the ventromedial hypothalamus. Single treatment with potentiated antibodies to mu-receptors increased the rate of self-stimulation and decreased the threshold of convulsive seizures. Administration of these antibodies for 7 days led to further activation of the positive reinforcement system and decrease in seizure thresholds. Distilled water did not change the rate of self-stimulation and seizure threshold.
The current therapy for Alzheimer's disease does not give patients a chance of recovery. Therefore, it is relevant to study the novel factors of influence, in particular microRNA, on the pathogenic mechanisms of amyloidosis. The aim of this work was to determine the effect of miR-101 on early predictors of amyloidosis in experimental Alzheimer's disease in animals. The study was carried out on 25 male rats of 14 months of age. A model of Alzheimer's disease was created by intrahippocampal administration of Aβ40 aggregates to animals. Ten days later, a 10-day course of nasal administration of miR-101 in liposomes was launched. The level of endogenous Aβ42 and cytokines (TNFα, IL-6 and IL-10) was determined in the supernatants of the nerve tissues of the target brain structures (hippocampus, olfactory bulbs, and olfactory tubercles). A neuroethological method of presenting smells of isovaleric acid and peanut butter was used to assess the olfactory system functional state in the experimental rats. In the course of polygraphic registration of the sleep-wakefulness cycle, the representation of wakefulness and individual sleep phases, as well as proportion of incomplete and complete sleep cycles were determined. It was shown that injection of Aβ40 aggregates into the hippocampus simulates an amyloidogenic state in the rat’s hippocampus and olfactory tubercles, but not in the olfactory bulbs. Moreover, a pro-inflammatory state was registered in the hippocampus of the animal brain (an increase in the concentration of pro-inflammatory cytokines TNFα and IL-6), while the cytokine level in the olfactory bulbs and tubercles did not change. When studying the functional state of olfactory analyzers in the rats with Alzheimer's disease, we revealed negative changes in behavioral response to the smell of isovaleric acid and peanut butter. In terms of somnograms, the Aβ40 toxicity caused reduction in the deep slow-wave sleep stage combined with deficiency of the paradoxical sleep phase, and predominance of incomplete sleep cycles. Nasal therapy with miR-101 in liposomes normalized the level of Aβ42 in the hippocampus and olfactory tubercles and decreased the level of proinflammatory cytokines in the hippocampus. MiR-101 prevented olfactory disfunctions in assessing smells of isovaleric acid and peanut butter, increased the ratio of deep slow-wave sleep and paradoxical sleep in the cycle structure and restored proportion of complete sleep cycles in animals. Thus, liposomal miR-101 has an anti-amyloidogenic and anti-inflammatory effect in rats with a model of Alzheimer's disease. It helps to restore the functional state of olfactory analyzer and optimize structural organization of the sleep-wakefulness cycle in sick animals.
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