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BACKGROUND AND AIMS: Amphetamine, besides its well known psychological and behavioral effects, was found to influence the immune functions. However, the mechanism of amphetamine-induced changes in the immune system remains unknown. In search of a possible mechanism of immunomodulating effect of amphetamine, in the present study we tested the involvement of sympathetic nervous system in that effect. RESULTS: After pretreatment with 6-hydroxydopamine (3×75 mg/kg, ip), we evaluated the effect of acute amphetamine (1 mg/ kg, ip) administration on natural killer cell cytotoxicity (NKCC; Cr-51 release assay) and the number of NK (LGL) cells in the peripheral blood and spleen in male Wistar rats. Amphetamineinduced stimulation of blood and splenic NKCC was completely blocked by chemical sympathectomy. Blood NKCC in amphetamine-injected rats was 260% higher in comparison to a control group. Rats pretreated with 6-hydroxydopamine before amphetamine administration showed over 70% lower NKCC then rats which received amphetamine without chemical sympathectomy. Similarly to the peripheral blood, over 190% increase in NKCC in rats injected with amphetamine was observed in the spleen. Splenic NKCC in rats pretreated with 6-hydroxydopamine was about 60% lower after amphetamine in comparison with rats without chemical sympathectomy. The similar effects were observed in the case of LGL number. CONCLUSIONS: The data clearly show that AMPH-induced stimulation of NK cells numbers and function both in the peripheral blood and spleen are mediated by peripheral sympathetic nervous system.
It is well known that the main site of the action of amphetamine (AMPH) are the catecholaminergic neurons located both in central nervous system and in the sympathetic nervous system (SNS). To analyse the potential role of the SNS in the mechanism of AMPHinduced changes in natural killer cells cytotoxicity (NKCC) rats were sympathectomized by 6-hydroxydopamine (6-OHDA, 3 × 50 mg/kg, i.p.) prior to AMPH (1 mg/kg, i.p.) administration. In a separate experiment, rats were pretreated with a α-adrenergic receptor antagonist phentolamine (5 mg/kg, i.p.), β-adrenergic receptor antagonist propranolol (5 mg/kg, i.p.) or both. NKCC (51Cr-release assay) and the number of LGL (NK cells) were evaluated in the peripheral blood and spleen. In the peripheral blood AMPH-induced stimulation of NKCC was completely blocked by 6-OHDA. The increase in LGL number in the peripheral blood evoked by AMPH was partially inhibited by sympathectomy. In the spleen both effects of AMPH i.e. reduction of NKCC and decrease in LGL number were completely reversed by 6-OHDA. β-antagonist attenuated the AMPH-induced changes in NKCC and LGL number in the peripheral blood and spleen. In contrast, changes in NKCC and LGL number were not affected by α-blockade. These data clearly show that both AMPH-induced stimulation of the peripheral blood NKCC and suppression of spleen NKCC are mediated by the SNS. Furthermore, catecholamines elevated by AMPH modulate the NKCC via β-adrenergic, but not α-adrenergic mechanism.
High frequency stimulation (HFS) of the subthalamic nucleus (STN) is a surgical therapy for improving of motor symptoms in Parkinson’s disease. In this study, we assessed the HFS effects on cytometric analysis of the peripheral blood lymphocytes (T, B, NK, T helper, T cytotoxic) in freely moving hemiparkinsonian rats. Before unilateral lesion of the right substantia nigra pars compacta (6-hydroxydopamine), all rats were divided into two behavioral groups: high-HR and low-LR responders in novelty test. As compared to the sham controls, HFS of STN signifi cantly increases NK cell percentage number (25.86 ± 9.68% vs. 18.79 ± 5.63%, P<0.05). In contrast, signifi cantly (P<0.05) lower B lymphocytes level in stimulated (18.86 ± 3.91%) then sham group (22.80 ± 4.63%) was observed. These general changes in NK and B lymphocyte numbers were refl ected in HR stimulated animals (31.08 ± 7.19% vs. 20.44 ± 5.65% for NK cells number and 17.67 ± 2.57% vs. 23.23 ± 3.37% for B lymphocyte, stimulated vs controls, respectively, P<0.01). On the other hand, signifi - cantly lower T lymphocyte level in LR stimulated animals in comparison to LR controls was found (38.32 ± 4.18% vs. 45.91 ± 5.68%). Moreover, signifi cant differences between stimulated HRS and LRS in the NK and T cytotoxic percentages were found (31.08 ± 7.19% vs. 17.63 ± 6.74%, P<0.05; 8.46 ± 1.83% vs. 12.29 ± 1.76%, P<0.01). The results emphasize the importance of individual differences in reactivity to novelty on immune response to HFS of STN.
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Although addiction to amphetamine (AMPH) is a serious social and medical problem, the data concerning AMPH – immune interactions are still not numerous. To analyze the mechanism of AMPH-induced changes in the function of the immune system, rats were pretreated with ß-adrenergic receptor antagonist propranolol (PROP; 5 mg/kg, i.p.) prior to AMPH (1 mg/kg, i.p.) administration. Natural Killer cells cytotoxicity (NKCC) (51Cr-release assay), the number of LGLs (NK cells) (Timonen method), leukocytes, lymphocytes and monocytes, and plasma corticosterone level (CORT) (RIA) were evaluated in the peripheral blood and spleen. In the peripheral blood increases in NKCC (+331%), as well as in LGL (+33%) and monocyte (+65%) number observed after AMPH were partially inhibited by PROP (respectively by 30%, 19%, and 30%) in contrast to lymphopenia (-19%) and granulocytosis (+65%) which were not affected by ß-blockade. In the spleen AMPH-induced decreases in NKCC (-25%) and in all the leukocyte populations number (approximately -30%) were completely blocked by PROP. Plasma CORT level, highly elevated by AMPH (+337%), was attenuated nearly by 50% under ß-adrenergic blockade. These data indicate that AMPH-induced enhancement of cytotoxic activity of NK cell is related to ß-adrenergic mechanism.
Contralateral nucleus accumbens shell (AcbS) lesions (Contra group) impaired (by about 20%) and ipsilateral AcbS lesions (Ipsi group) facilitated (by about 30%) motivational aspects of ventral tegmental area (VTA) stimulation-induced feeding or exploration which manifested as respective alterations in latency to reaction. Present work was aimed to examine how this motivational reorganization of AcbSVTA circuitry affect on blood leukocytes and their subsets (morphological method). As compared to the respective sham animals, the chronic VTA stimulation and unilateral lesion of the AcbS caused a significant decrease in total leukocyte and lymphocyte numbers in Ipsi and Contra groups. Both groups showed also significant decreases in total leukocyte and lymphocyte numbers on the 2nd day after unilateral lesion of the AcbS. On the 14th VTA stimulation day following unilateral lesion of the AcbS total leukocyte and a large granular lymphocyte (LGL) number was higher in Ipsi group in relation to Contra group and in comparison with the respective sham group. Increased motivational drive associated with facilitation reactivity of the ipsilateral VTA to lesioning AcbS enhance total leukocyte number, especially LGL cells that are critical to the innate immune system.
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