Publicēti raksti (MF) / Published Articles

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Browsing Publicēti raksti (MF) / Published Articles by Author "Dzirkale, Zane"

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    Carnitine congener mildronate protects against stress- and haloperidol-induced impairment in memory and brain protein expression in rats
    (Elsevier, 2014) Beitnere, Ulrika; Dzirkale, Zane; Isajevs, Sergejs; Rumaks, Juris; Svirskis, Simons; Klusa, Vija
    The present study investigates the efficacy of mildronate, a carnitine congener, to protect stress and haloperidol-induced impairment of memory in rats and the expression of brain protein biomarkers involved in synaptic plasticity, such as brain-derived neurotrophic factor (BDNF), acetylcholine esterase and glutamate decarboxylase 67 (GAD67). Two amnesia models were used: 2 h immobilization stress and 3-week haloperidol treatment. Stress caused memory impairment in the passive avoidance test and induced a significant 2-fold BDNF elevation in hippocampal and striatal tissues that was completely inhibited by mildronate. Mildronate decreased the level of GAD67 (but not acetylcholine esterase) expression by stress. Haloperidol decrease by a third hippocampal BDNF and acetylcholine esterase (but not GAD67) expression, which was normalized by mildronate; it also reversed the haloperidol-induced memory impairment in Barnes test. The results suggest the usefulness of mildronate as protector against neuronal disturbances caused by stress or haloperidol.
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    Intranasal Administration of Extracellular Vesicles Derived from Human Teeth Stem Cells Improves Motor Symptoms and Normalizes Tyrosine Hydroxylase Expression in the Substantia Nigra and Striatum of the 6-Hydroxydopamine-Treated Rats
    (AlphaMed Press Wiley, 2019-04-22) Narbute, Karīna; Piļipenko, Vladimirs; Pupure, Jolanta; Dzirkale, Zane; Jonavičė, Ugnė; Tunaitis, Virginijus; Kriaučiūnaitė, Karolina; Jarmalavičiūtė, Akvilė; Jansone, Baiba; Kluša, Vija; Pivoriūnas, Augustas
    Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting millions of people worldwide. At present, there is no effective cure for PD; treatments are symptomatic and do not halt progression of neurodegeneration. Extracellular vesicles (EVs) can cross the blood–brain barrier and represent promising alternative to the classical treatment strategies. In the present study, we examined therapeutic effects of intranasal administration of EVs derived from human exfoliated deciduous teeth stem cells (SHEDs) on unilateral 6‐hydroxydopamine (6‐OHDA) medial forebrain bundle (MFB) rat model of PD. CatWalk gait tests revealed that EVs effectively suppressed 6‐OHDA‐induced gait impairments. All tested gait parameters (stand, stride length, step cycle, and duty cycle) were significantly improved in EV‐treated animals when compared with 6‐OHDA‐lesion group rats. Furthermore, EVs slowed down numbers of 6‐OHDA‐induced contralateral rotations in apomorphine test. Improvements in motor function correlated with normalization of tyrosine hydroxylase expression in the striatum and substantia nigra. In conclusion, we demonstrated, for the first time, the therapeutic efficacy of intranasal administration of EVs derived from SHEDs in a rat model of PD induced by 6‐OHDA intra‐MFB lesion. Our findings could be potentially exploited for the development of new treatment strategies against PD.
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    Lunasin-induced behavioural effects in mice: Focus on the dopaminergic system
    (Elsevier, 2013) Dzirkale, Zane; Rumaks, Juris; Svirskis, Simons; Mazina, Olga; Allikalt, Anni; Rinken, Ago; Jekabsons, Kaspars; Muceniece, Ruta; Klusa, Vija
    The present study for the first time is devoted to identify central effects of synthetic lunasin, a 43 amino acid peptide. A markedly expressed neuroleptic/cataleptic effect was observed at low (0.1–10 nmol/mouse) centrally administered doses in male C57Bl/6 mice. Lunasin considerably reduced the amphetamine hyperlocomotion but weakly apomorphine climbing behaviour. No influence on ketamine and bicuculline effects was observed. Binding assay studies demonstrated modest affinity of lunasin for the dopamine D1 receptor (Ki = 60±15 M). In a functional assay of cAMP accumulation on live cells lunasin antagonised apomorphine effect on D1 receptor activation (pEC50 = 6.1±0.3), but had no effect in cells expressing D2 receptors. The obtained data suggest that lunasin’s action at least in part is provided via dopaminergic D1 receptor pathways. However, other non-identified mechanisms (probably intracellular) may play an important role in lunasin’s central action. Nevertheless further studies of lunasin are promising, particularly taking into account a necessity for novel type of antipsychotic drugs
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    γ1- and γ2-melanocyte stimulating hormones induce central anxiogenic effects and potentiate ethanol withdrawal responses in the elevated plus-maze test in mice
    (Elsevier, 2009) Jansone, Baiba; Rumaks, Juris; Dzirkale, Zane; Pupure, Jolanta; Svirskis, Šimons; Muceniece, Ruta; Klusa, Vija
    Little is known about the endogenous functions of γ1- and γ2-melanocyte stimulating hormones (γ1- and γ2-MSH). Although γ-MSHs bind to melanocortin receptor subtypes 3 and 4, we have previously shown that these peptides also influence non-melanocortinergic processes, such as dopaminergic and GABAergic. The aim of this study was to determine the effects of γ1- and γ2-MSH (at doses 0.3, 1 and 2 nmol/mouse/5 μl) on the anxiety levels in mice in elevated plus maze. Three experimental paradigms were performed to assess the effects of peptides on: a) ethanol withdrawal; b) acute ethanol-induced anxiolytic action; c) peptides per se. We used ethanol as the model substance, since its action involves either dopaminergic/GABAergic or melanocortinergic processes. γ-MSHs were administered intracisternally in mice and behavioural responses were assessed in the elevated plus maze test. This study provides the first demonstration of an anxiogenic effect of γ1- and γ2-MSH, their synergistic/additive effect on ethanol withdrawal-induced anxiety behaviour, and an antagonism of peptides involved in the anxiolytic action of ethanol. Furthermore, results suggest that γ-MSHs belong to an anxiogenic peptide family that may play an important role in anxiety disorders as well as in the development of alcohol dependence and/or alcohol withdrawal-induced behaviours.