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1.
Int J Dev Neurosci ; 78: 7-18, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31369794

ABSTRACT

Perinatal hypoxia-ischemia is one of the most common causes of perinatal brain injury and subsequent neurological disorders in children. The aim of this work was to evaluate the potential antioxidant and neuroprotective effects of N-arachidonoyl-dopamine (NADA) in the model of acute neonatal hypoxia (ANH) in rat pups. Male and female Wistar rats were exposed to a hypoxic condition (8% oxygen for 120 min) at postnatal day 2 (P2). Transcription factor HIF1-α and glutathione peroxidases GPx2 and GPx4 gene expression was increased in rat brains in the hypoxic group compared to control 1.5 h but not 4 days after ANH. There were no post-hypoxic changes in reduced (GSH) and oxidised (GSSG) glutathione levels in the brain of rat pups 1.5 h and 4 d after hypoxia. Hypoxic rats displayed retarded performance in the righting reflex and the negative geotaxis tests. ANH resulted in increased ambulation in Open field test and impaired retention in the Barnes maze task under stressful conditions as compared with the control group. Treatment with NADA significantly attenuated the delayed development of sensorimotor reflexes and stress-evoked disruption of memory retention in hypoxic rats but had no effect on the hypoxia-induced hyperactivity. In rats exposed to hypoxia, treatment with NADA decreased GPx2 gene expression and increased GSH/GSSG ratio in whole brains 1.5 h after ANH. These results suggest that the long-lasting beneficial effects of NADA on hypoxia-induced neurobehavioural deficits are mediated, at least in part, by its antioxidant properties.


Subject(s)
Antioxidants/metabolism , Arachidonic Acids/pharmacology , Brain/drug effects , Dopamine/analogs & derivatives , Hypoxia-Ischemia, Brain/drug therapy , Neuroprotective Agents/pharmacology , Animals , Arachidonic Acids/therapeutic use , Brain/metabolism , Dopamine/pharmacology , Dopamine/therapeutic use , Female , Glutathione/metabolism , Glutathione Peroxidase/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Ischemia, Brain/metabolism , Male , Maze Learning/drug effects , Motor Activity/drug effects , Neuroprotective Agents/therapeutic use , Rats , Rats, Wistar , Reflex, Righting/drug effects
2.
Bull Exp Biol Med ; 167(1): 43-46, 2019 May.
Article in English | MEDLINE | ID: mdl-31177459

ABSTRACT

We performed a comparative study of the cytotoxic effect of endocannabinoid N-arachidonoyl dopamine (AA-DA) on cultured stromal cells of ectopic and eutopic endometrium. It was found that AA-DA in the concentration range of 1-20 µM produces more selective cytotoxic effect on the stromal cells of the ectopic endometrium due to interaction with cannabinoid type 1 receptor. In concentrations below 1 µM, AA-DA stimulated the proliferation of stromal cells of the eutopic endometrium and did not affect the division of ectopic endometrium cells. This effect was realized due to its interaction with cannabinoid type 2 receptor.


Subject(s)
Cell Proliferation/drug effects , Cell Survival/drug effects , Dopamine/metabolism , Endometriosis/metabolism , Endometrium/metabolism , Stromal Cells/cytology , Stromal Cells/drug effects , Camphanes/pharmacology , Cannabinoid Receptor Antagonists/pharmacology , Capsaicin/analogs & derivatives , Capsaicin/pharmacology , Endometrium/cytology , Female , Humans , Pyrazoles/pharmacology , Receptor, Cannabinoid, CB1/antagonists & inhibitors , Receptor, Cannabinoid, CB1/metabolism , Receptor, Cannabinoid, CB2/antagonists & inhibitors , Receptor, Cannabinoid, CB2/metabolism , Rimonabant/pharmacology
3.
Biochemistry (Mosc) ; 82(11): 1367-1372, 2017 Nov.
Article in English | MEDLINE | ID: mdl-29223163

ABSTRACT

Neuroprotective properties of endocannabinoids N-arachidonoyl dopamine (NADA) and N-docosahexaenoyl dopamine (DHDA) were examined in neuronal precursor cells differentiated from human induced pluripotent stem cells and subjected to oxidative stress. Both compounds exerted neuroprotective activity, which was enhanced by elevating the concentration of the endocannabinoids within the 0.1-10 µM range. However, both agents at 10 µM concentration showed a marked toxic effect resulting in death of ~30% of the cells. Finally, antagonists of cannabinoid receptors as well as the receptor of the TRPV1 endovanilloid system did not hamper the neuroprotective effects of these endocannabinoids.


Subject(s)
Arachidonic Acids/pharmacology , Dopamine/analogs & derivatives , Neural Stem Cells/drug effects , Neuroprotective Agents/pharmacology , Pluripotent Stem Cells/cytology , Cannabinoid Receptor Agonists/pharmacology , Dopamine/pharmacology , Dose-Response Relationship, Drug , Endocannabinoids/pharmacology , Humans , Oxidative Stress , TRPV Cation Channels/antagonists & inhibitors
4.
Biomed Khim ; 63(5): 385-391, 2017 Oct.
Article in Russian | MEDLINE | ID: mdl-29080869

ABSTRACT

The aim of this study was to determine the changes of metabolomic profiles in embryonic culture media (ECM) for the evaluation of quality and implantation potential of human embryos. ECM (n=163) were collected on day 5 before transfer or cryopreservation. Some embryos were used in preimplantation genetic screening for detection of aneuploidy karyotypes. Samples were subdivided into groups according to embryo morphological classification (by Gardner), genetic analysis and implantation data. ECM were extracted with methanol, precipitates were separated by centrifugation and metabolite production of individual embryo was analysed by LC-MS (the positive ion mode). After peak detection and retention time alignment, data were analysed using the PCA algorithm. MS fingerprinting analysis of embryo culture medium showed significant differences between morphologically divided groups. Intragroup comparisons did not reveal differences between subclasses. Genetic screening of embryos revealed 33 aneuploid karyotypes. It was shown that chromosome number did not affect the metabolite profiles comparing with the normal group. The culture media of embryos that were positive or negative for successful implantation showed specific signatures that allowed to distinguish embryos with different outcomes.The characterization of ECMs by LC-MS may facilitate more accurate selection of the best embryo for the implantation, improving single-embryo transfer and thus eliminating the risk and undesirable effects of multiple pregnancies.


Subject(s)
Culture Media/chemistry , Embryo Culture Techniques , Metabolome , Aneuploidy , Embryo Implantation , Embryo Transfer , Embryo, Mammalian/metabolism , Humans , Karyotyping , Metabolomics
5.
Bull Exp Biol Med ; 163(2): 272-275, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28730390

ABSTRACT

Differential expression of type 1 cannabinoid receptors (CR1) was evaluated at different stages of human skin fibroblast transformation into terminally differentiated neurons. Immunocytochemical staining detected no CR1 on fibroblasts, but their transformation into induced pluripotent stem cells was accompanied by marked stimulation of CR1 expression. In neuronal precursors, the receptors were located mainly on cell bodies and at the base of their processes. This distribution was retained at the terminal stage of differentiation of induced pluripotent stem cells into neurons.


Subject(s)
Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/metabolism , Receptors, Cannabinoid/metabolism , Cell Differentiation/genetics , Cell Differentiation/physiology , Cellular Reprogramming/genetics , Cellular Reprogramming/physiology , Fibroblasts/cytology , Fibroblasts/metabolism , Humans , Skin/cytology
7.
Bull Exp Biol Med ; 156(4): 461-4, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24771427

ABSTRACT

We studied the effect of endocannabinoid N-arachidonoyl dopamine on spontaneous bioelectric activity of cultured hippocampal neurons in a model of hypoxia/reoxygenation. Incubation under hypoxic conditions induced irreversible decrease in spontaneous bioelectric activity of neurons and their death. Application of N-arachidonoyl dopamine during hypoxia and in the post-hypoxic period preserved bioelectric activity and viability of neurons. The protective effect of N-arachidonoyl dopamine was primarily mediated by type I cannabinoid receptors.


Subject(s)
Arachidonic Acids/pharmacology , Dopamine/analogs & derivatives , Hippocampus/cytology , Neuroprotective Agents/pharmacology , Action Potentials , Animals , Cell Hypoxia , Cells, Cultured , Dopamine/pharmacology , Drug Evaluation, Preclinical , Mice , Nerve Net/drug effects , Nerve Net/physiology , Neurons/physiology , Primary Cell Culture
8.
Bull Exp Biol Med ; 151(1): 30-2, 2011 May.
Article in English | MEDLINE | ID: mdl-22442796

ABSTRACT

We studied the effects of endocannabinoid anandamide and its cyclooxygenase derivative prostamide E2 on cultured cerebellar granular cells and C6 glioma cells from rats. Prostamide E2 prevented apoptosis in cerebellar neurons induced by potassium deprivation of cultures, while anandamide had no neuroprotective properties. Prostamide E2 did not modulate the survival rate of glioma cells, while anandamide produced a cytotoxic effect. Our results indicate that cyclooxygenase transformation of anandamide is followed by the loss of antitumor activity of this agent. By contrast, prostamide E2 exhibited strong neuroprotective properties.


Subject(s)
Arachidonic Acids/metabolism , Dinoprostone/analogs & derivatives , Neurons/drug effects , Neuroprotective Agents/pharmacology , Polyunsaturated Alkamides/metabolism , Potassium/pharmacology , Animals , Apoptosis/drug effects , Arachidonic Acids/pharmacology , Biotransformation , Cell Survival/drug effects , Cells, Cultured , Cerebellum/cytology , Cerebellum/drug effects , Cerebellum/metabolism , Dinoprostone/metabolism , Dinoprostone/pharmacology , Dose-Response Relationship, Drug , Endocannabinoids , Glioma/metabolism , Glioma/pathology , Neurons/cytology , Neurons/metabolism , Neuroprotective Agents/metabolism , Polyunsaturated Alkamides/pharmacology , Potassium/metabolism , Potassium Deficiency/metabolism , Primary Cell Culture , Prostaglandin-Endoperoxide Synthases/metabolism , Rats
10.
Eur J Neurosci ; 26(11): 3207-14, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18028114

ABSTRACT

In the terrestrial snail a direct monosynaptic glutamatergic connection between the primary sensory neuron and a premotor interneuron involved in withdrawal behaviour can be functionally identified using electrophysiological techniques. We investigated the involvement of cannabinoids in regulation of this synaptic contact. The results demonstrate that the specific binding sites for agonists to mammalian type 1 cannabinoid receptors (CB1Rs) exist in the snail's nervous system. Application of a synthetic cannabinoid agonist anandamide selectively changed the efficacy of synaptic contacts between the identified neurons. A decrease in the long-term synaptic facilitation of the synaptic contact elicited by high-frequency nerve tetanization in the presence of cannabinoid agonist anandamide was observed, suggesting a possible role of endocannabinoids in regulation of plasticity at this synaptic site. The selective antagonist of CB1Rs [N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide] AM251 bath application was changing the efficacy of the synaptic contact only when the postsynaptic neuron had been intracellularly activated before its application. This observation implies an involvement of endocannabinoids in plasticity phenomena induced by activity in the postsynaptic target. Additional support of endocannabinoid involvement in synaptic function at this site was given by experiments in which AM251 blocked the short-term suppression of synaptic excitation evoked by low-frequency nerve tetanization, a phenomenon qualitatively similar to cannabinoid-dependent synaptically evoked suppression of excitation demonstrated in the mammalian nervous system. The results of the present study suggest an involvement of cannabinoids in the regulation of synaptic efficacy. Further, anandamide could be a candidate for an endogenous neuromessenger involved in plasticity processes.


Subject(s)
Cannabinoids/metabolism , Neurons/cytology , Synapses/physiology , Animals , Arachidonic Acids/pharmacology , Cannabinoid Receptor Modulators/pharmacology , Cyclohexanols/metabolism , Dose-Response Relationship, Radiation , Electric Stimulation , Endocannabinoids , Excitatory Postsynaptic Potentials/drug effects , Excitatory Postsynaptic Potentials/physiology , Excitatory Postsynaptic Potentials/radiation effects , Nervous System/cytology , Neurons/physiology , Patch-Clamp Techniques/methods , Piperidines/pharmacology , Polyunsaturated Alkamides/pharmacology , Pyrazoles/pharmacology , Receptor, Cannabinoid, CB1/agonists , Receptor, Cannabinoid, CB1/antagonists & inhibitors , Receptor, Cannabinoid, CB1/physiology , Snails/cytology , Snails/drug effects , Snails/physiology , Synapses/drug effects , Tritium/metabolism
11.
Bull Exp Biol Med ; 142(1): 39-42, 2006 Jul.
Article in English, Russian | MEDLINE | ID: mdl-17369898

ABSTRACT

We studied the effect of cannabinoid receptor agonists anandamide and WIN 55,212-2 on the central pain syndrome induced by intraspinal injection of penicillin sodium salt in rats. Cannabinoids suppressed allodynia and spontaneous attacks in rats with the central pain syndrome. The analgesic effect was most pronounced after intrathecal injection of cannabinoid receptor agonist in a dose of 100 microg in 10 microl. After systemic treatment the analgesic effect was produced by only WIN 55,212-2 in a dose of 1 mg/kg. WIN 55,212-2 was superior to anandamide by the duration and intensity of the effect on allodynia and spontaneous attacks.


Subject(s)
Arachidonic Acids/metabolism , Cannabinoid Receptor Agonists , Morpholines/metabolism , Naphthalenes/metabolism , Pain/drug therapy , Pain/metabolism , Polyunsaturated Alkamides/metabolism , Analysis of Variance , Animals , Arachidonic Acids/therapeutic use , Benzoxazines , Dose-Response Relationship, Drug , Endocannabinoids , Injections, Spinal , Male , Morpholines/therapeutic use , Naphthalenes/therapeutic use , Pain/chemically induced , Pain Measurement , Penicillin V/administration & dosage , Penicillin V/toxicity , Polyunsaturated Alkamides/therapeutic use , Rats , Rats, Wistar
12.
Bull Exp Biol Med ; 142(4): 425-7, 2006 Oct.
Article in English, Russian | MEDLINE | ID: mdl-17415428

ABSTRACT

N-Docosahexaenoyl dopamine exhibited antioxidant activity in the test with a stable oxygen radical galvinoxyl. This compound produced a dose-dependent protective effect on cultured granular cells from rat cerebellum under conditions of oxidative stress. N-Docosahexaenoyl dopamine decelerated the development of symptoms of Parkinson's disease in mice receiving neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.


Subject(s)
Antioxidants/pharmacology , Cerebellum/physiology , Dopamine/analogs & derivatives , Neuroprotective Agents/pharmacology , Animals , Cells, Cultured , Cerebellum/cytology , Cerebellum/drug effects , Dopamine/pharmacology , Dose-Response Relationship, Drug , Neurons/drug effects , Neurons/physiology , Oxidative Stress/drug effects , Parkinsonian Disorders/physiopathology , Rats
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