Chronic treatment with enhancer drugs modifies the gene expression of selected parameters related to brain plasticity in rats under stress conditions.

Selegiline, also known as L-deprenyl, and (2R)-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine (BPAP) were found to induce enhancement of monoamine neurotransmission in low and very low doses. In addition, these enhancers may modify glutamatergic neurotransmission. The aim of the present study was to test the hypothesis that under stress conditions, chronic treatment with enhancer drugs has a positive impact on the glutamatergic system and other parameters related to brain plasticity, stress-related systems, and anxiety behavior. We exposed male Wistar rats to a chronic mild stress procedure combined with chronic treatment with two synthetic enhancer drugs. The gene expression of GluR1, an AMPA receptor subunit was reduced by repeated treatment with deprenyl in the hippocampus and with both BPAP and deprenyl in the prefrontal cortex. A significant reduction of NMDA receptor subunit GluN2B expression was observed in the hippocampus but not in the prefrontal cortex. Deprenyl treatment led to an enhancement of hippocampal BDNFmRNA concentrations in stress-exposed rats. Treatment with enhancer drugs failed to induce significant changes in stress hormone concentrations or anxiety behavior. In conclusion, the present study in chronically stressed rats showed that concomitant treatment with enhancer drugs did not provoke substantial neuroendocrine changes, but modified gene expression of selected parameters associated with brain plasticity. Observed changes may indicate a positive influence of enhancer drugs on brain plasticity, which is important for preventing negative consequences of chronic stress and enhancement of stress resilience. It may be suggested that the changes in glutamate receptor subunits induced by enhancer drugs are brain region-specific and not dose-related.

Delta-Opioid Receptors Play a Role in the Control of Selected Parameters Related to Stress and Brain Plasticity Under Non-stress and/or Stress Conditions.

There is some evidence that delta-opioid receptors may be involved in the brain processes related to neuroprotection. The aim of the present studies was to test the hypothesis that endogenous opioid peptides acting via delta-opioid receptors can protect against stress-induced changes in factors related to brain plasticity and stress hormone release. Forty male adult Wistar rats were used. Half of the animals were exposed to sustained partial restraint stress (hypokinesis) lasting 48 h. Rats were treated with vehicle (isotonic saline) or the delta-opioid receptor antagonist naltrindole (3 mg/kg/ml, s.c.) six times a day. The stressfulness of the model was confirmed by increased plasma concentrations of corticosterone and prolactin, the increase in anxiety behavior in the open field test, as well as the reduction of BrdU incorporation into newly formed DNA in the hippocampus. Treatment with naltrindole potentiated the stress-induced rise in aldosterone concentrations. The blockade of delta-opioid receptors resulted in a decrease in hippocampal BDNF gene expression independently of control or stress conditions. Treatment with naltrindole enhanced plasma concentrations of copeptin, a stable precursor of vasopressin. In conclusion, these results suggest that endogenous opioid peptides might play an inhibitory role in aldosterone release under stress conditions and in the control of vasopressin release independently of stress exposure. Endogenous opioids might stimulate hippocampal gene expression of the important neurotrophic factor BDNF via delta-opioid receptors.

Increased gene expression of selected vesicular and glial glutamate transporters in the frontal cortex in rats exposed to voluntary wheel running.

Though positive effects of exercise on mood and well being are well recognised, the central regulatory mechanisms are still not fully understood. The present study was aimed to testing the hypothesis that voluntary wheel running activates the gene expression of glutamate transporters in the brain cortex of rats. The animals were assigned to the control and voluntary wheel running groups. Voluntary wheel running rats had free access to a stainless steel activity wheel for 3 weeks. The daily running distance gradually increased to 6.21 ± 1.05 km by day 21. Vesicular glutamate transporter 3 (VGLUT3) mRNA levels in the frontal cortex were significantly elevated in the group of running animals compared to the values in sedentary controls, while the expression of other vesicular transporters were unchanged. The concentrations of mRNA coding for glial glutamate transporter 1 (GLT-1), but not glutamate aspartate transporter (GLAST) were increased by running. Voluntary wheel running resulted in an elevation of plasma corticosterone and increased expression of brain derived neurotrophic factor (BDNF) in the frontal cortex. In conclusion, chronic voluntary wheel running results in increased gene expression of VGLUT3 and GLT-1 in the brain cortex without changes in other glutamate transporter subtypes.

[Apoptosis in T-lymphocytes and its significance]. / Apoptóza T-lymfocytov a jej význam.

Apoptosis is an integral process of the immune system development and existence. Due to the ability of lymphocytes to follow the apoptotic pathway a very negative effect--the escape of tumor cells population from the immune system control is observed. Multiplying malignant cells during the tumor progression cause the synergic effect of tumor cells apoptosis blocation and unfavourable T-lymphocytes apoptosis induction. The lymphocyte cells apoptosis can be induced by the tumor produced substances as well as the receptor spectrum exprimated by the tumor cells. Physical and chemical anti-cancer therapy causing the non-selective apoptosis induction also contributes substantially to the immune system weakening. Fas-receptor (FasR) is constitutionally expressed on the activated T-lymphocyte surface. The common sign of the lung, colorectal, breast and other carcinomas is the presence of the surfacial Fas-ligand (FasL). During the infiltration process of tumor by the lymphocytes the FasR/FasL interaction is present, which is probably the most effective trigger mechanism of the T cells apoptosis. The contact of T-lymphocytes and tumor cells for the active antitumor immunity is inevitable. The apoptotic pathways modulation of T-lymphocytes provides a space for FasR/FasL induction influence and thus the anticancer immunity efficiency determination.