Effect of Trehalose Disaccharide on Activation of Microglia and Indices of Systemic Inflammation in an Experimental Model of Alzheimer's Disease.

In an experimental model of Alzheimer's disease in mice, oral administration of trehalose disaccharide reduces neuroinflammation assessed by the expression level of microglia activation marker Iba1 and affects the neutrophil degranulation activity. A potential anti-inflammatory effect of 4% trehalose solution associated with a decrease in the activity of leukocyte elastase in plasma was revealed.

Restoration of Parkinson's Disease-Like Deficits by Activating Autophagy through mTOR-Dependent and mTOR-Independent Mechanisms in Pharmacological and Transgenic Models of Parkinson's Disease in Mice.

We studied the possibilities of inhibition of neurodegeneration in MPTP-induced model of Parkinson's disease (PD) in C57Bl/6J mice and transgenic model of early PD stage (5-monthold B6.Cg-Tg(Prnp-SNCA*A53T)23Mkle/J mice) by autophagy activation through mTOR-dependent and mTOR-independent pathways with rapamycin and trehalose, respectively. Therapy with autophagy inducers in a "postponed" mode (7 days after MPTP intoxication) restored the expression of the dopaminergic neuron marker tyrosine hydroxylase and markedly improved cognitive function in the conditioned passive avoidance response (CPAR; fear memory). The transgenic model also showed an increase in the expression of tyrosine hydroxylase in the nigrostriatal system of the brain. An enhanced therapeutic effect of the combined treatment with the drugs was revealed on the expression of tyrosine hydroxylase, but not in the CPAR test. Thus, activation of both pathways of autophagy regulation in PD models with weakened neuroinflammation can restore the dopaminergic function of neurons and cognitive activity in mice.

Hypotensive effect of retabolil correcting the concentration of aldosterone during stress exposures.

Male rats were exposed to single or repeated (19 days) cold treatment (4°C) and non-cold stress (60-min shaking on a laboratory shuttle device). Retabolil had a hypotensive effect, which was accompanied by the prevention of a stress-induced increase in the concentration of a hypertensive hormone aldosterone. Under conditions of repeated stress, these effects were realized via µ-opioid receptors. Our results suggest that retabolil can be used as a hypotensive and aldosterone-blocking agent, at least during stress exposure in animals (and probably in humans).

Effects of dehydroepiandrosterone sulfate on the conversion of corticosterone into 11-dehydrocorticosterone in stress: a regulatory scheme.

In male rats, repeated but not single exposures to stress increased the conversion of corticosterone (CS) to 11-dehydrocorticosterone (11-DHCS), particularly on the background of administration of dehydroepiandrosterone sulfate (DHEAS). Naltrexone given 20 min before DHEAS at a dose of 0.1 mg/kg, at which it selectively blocks mu opioid receptors, prevented this effect of DHEAS, which is evidence that it is mediated by mu opioid receptors. This action of DHEAS involved endogenous ACTH and was thus mediated by central regulatory mechanisms. Our results, along with published data, lead to the first proposed scheme for the physiological regulation of the interconversion of CS and 11-DHCS in conditions of repeated stress with the involvement of DHEAS and mu opioid receptors.

Prolonged decrease in stress reactivity caused by dehydroepiandrosterone sulfate.

In male rats exposed to repeated stress, the decrease in stress reactivity produced by subcutaneous injection of dehydroepiandrosterone sulfate (recorded by the decrease in stress-induced concentrations of corticosterone and adrenocorticotropic hormone in blood plasma) was observed 1-6 days postinjection and involved central regulatory mechanisms.

Ratio between the contents of 11-dehydrocorticosterone and corticosterone after acute and repeated stress: effect of dehydroepiandrosterone sulfate.

Acute stress was accompanied by reduction of 11-dehydrocorticosterone to corticosterone in male rats. The reverse reaction predominated during repeated stress and increased after administration of dehydroepiandrosterone sulfate. Treatment with mu-opioid receptor antagonist naltrexone in a dose of 0.1 mg/kg 20 min before administration of dehydroepiandrosterone sulfate abolished this effect.

Stress-limiting effect of dehydroepiandrosterone sulfate and its mechanism.

Dehydroepiandrosterone sulfate prevented the increase in corticosterone level in rats induced by repeated exposure to stress. The mu-opioid receptor blocker naltrexone administered in a dose of 0.1 mg/kg 20 min before treatment with dehydroepiandrosterone sulfate abolished the effect of this agent. Dehydroepiandrosterone sulfate and naltrexone had no effect on rats after acute stress.

Effects of alternative social experience on the sexual function of male mice.

The relevance of the social contact test "Wall" for evaluation of sexual motivation of male mice was tested and confirmed. Motivation of C57BL/6J male mice with alternative social experience (winners and victims in 10 and 20 daily male-male confrontations) was evaluated. Elevated primary sexual interest was detected in aggressive animals after 10 confrontations, while in submissive animals this interest was decreased; however after 20 confrontations sexual motivation in both groups was characterized by rapid exhaustion and low basal level of testosterone. Hence, the sexual function of male mice is inhibited under conditions of long social conflicts irrespective of previous experience of victories or defeats in male-male confrontations.