Publicēti raksti (MF) / Published Articles

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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.
Very low doses of muscimol and baclofen ameliorate cognitive deficits and regulate protein expression in the brain of a rat model of streptozocin-induced Alzheimer's disease
(Elsevier, 2018-01-05) Pilipenko, Vladimirs; Narbute, Karina; Beitnere, Ulrika; Rumaks, Juris; Pupure, Jolanta; Jansone, Baiba; Klusa, Vija
Recent studies devoted to neuroprotection have focused on the role of the gamma-aminobutyric acid (GABA) system in regulating neuroinflammatory processes which play a key role in the neurodegenerative processes observed in Alzheimer's disease (AD) by inducing glial cell overactivation and impairing neurotransmission. Data on the efficacy of classical GABA-A and GABA-B receptor agonists (muscimol and baclofen, respectively) in animal models of AD are not available. Moreover, no published studies have examined the ability of optimal doses of these compounds to prevent neuroinflammation, the alterations in neurotransmission and cognitive deficits. In the present study, we used a non-transgenic rat model of AD obtained by intracerebroventricular streptozocin (STZ) injection and assessed the effects of muscimol and baclofen at very low doses (0.01-0.05mg/kg) on spatial memory and the expression of cortical and hippocampal proteins related to neuroinflammation, namely proteins involved in astroglial functions (glial fibrillary acidic protein, GFAP), GABA synthesis (GABA synthesizing enzyme, glutamic acid decarboxylase 67, GAD67) and acetylcholine degradation (acetylcholine esterase). The presented study demonstrated that in a rat model of STZ-induced AD both muscimol and baclofen at the tested doses exerted memory-enhancing and anti-inflammatory effects, as well as normalization of acetylcholine esterase and GABA expression. We suggested that the function of very low doses of GABA receptor agonists differs from typical GABA-related inhibition and may be mediated by the allosteric sites of GABA receptors or other non-specific cell regulatory pathways.
Burnout syndrome among psychiatric trainees in 22 countries: Risk increased by long working hours, lack of supervision, and psychiatry not being first career choice
(Elsevier, 2016-02) Jovanović, N.; Podlesek, A.; Volpe, U.; Barrett, E.; Ferrari, S.; Rojnic Kuzman, M.; Wuyts, P.; Losevich, M. A.; etc
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
DNA damage causes TP53-dependent coupling of self-renewal and senescence pathways in embryonal carcinoma cells
(Taylor&Francis, 2013) Jackson, Thomas R.; Salmina, Kristine; Huna, Anda; Inashkina, Inna; Jankevics, Eriks; Riekstina, Una; Kalnina, Zane; Ivanov, Andrey; Townsend, Paul A .; Cragg, Mark S.; Erenpreisa, Jekaterina

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