Influence of Hemantane on Changes in Ca2+ and Na+ Caused by Activation of NMDA Channels in Cultured Rat Brain Neurons

Воронина, Н. А.; Lisinа, Oksana; Krasilnikova, Irina; Kucheryanu, V. G.; Kapitsa, I. G.; Воронина, Т. А.; Surin, Alexander

doi:10.1134/s1819712421010165

Cited by 3 publications

(2 citation statements)

References 19 publications

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“…In addition, the overexpression of alpha-synuclein increases the phosphorylation of N-methyl-D-aspartate (NMDA) receptors, thereby increasing the formation of NR1 and NR2B subunits and the sensitivity of NMDA receptors to developing glutamate excitotoxicity [ 124 ]. Increased levels of glutamate in the intercellular space activates glutamate NMDA receptors, leading to a calcium overload and the death of DA neurons [ 125 , 126 , 127 ]. Alpha-synuclein can also enhance glutamate excitotoxicity by accelerating α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor signaling [ 128 ].…”

Section: Parkinson’s Disease Is a Form Of Synucleinopathymentioning

confidence: 99%

Synuclein Proteins in MPTP-Induced Death of Substantia Nigra Pars Compacta Dopaminergic Neurons

et al. 2022

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Parkinson’s disease (PD) is one of the key neurodegenerative disorders caused by a dopamine deficiency in the striatum due to the death of dopaminergic (DA) neurons of the substantia nigra pars compacta. The initially discovered A53T mutation in the alpha-synuclein gene was linked to the formation of cytotoxic aggregates: Lewy bodies in the DA neurons of PD patients. Further research has contributed to the discovery of beta- and gamma-synucleins, which presumably compensate for the functional loss of either member of the synuclein family. Here, we review research from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity models and various synuclein-knockout animals. We conclude that the differences in the sensitivity of the synuclein-knockout animals compared with the MPTP neurotoxin are due to the ontogenetic selection of early neurons followed by a compensatory effect of beta-synuclein, which optimizes dopamine capture in the synapses. Triple-knockout synuclein studies have confirmed the higher sensitivity of DA neurons to the toxic effects of MPTP. Nonetheless, beta-synuclein could modulate the alpha-synuclein function, preventing its aggregation and loss of function. Overall, the use of knockout animals has helped to solve the riddle of synuclein functions, and these proteins could be promising molecular targets for the development of therapies that are aimed at optimizing the synaptic function of dopaminergic neurons.

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Section: Parkinson’s Disease Is a Form Of Synucleinopathymentioning

confidence: 99%

Synuclein Proteins in MPTP-Induced Death of Substantia Nigra Pars Compacta Dopaminergic Neurons

et al. 2022

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“…In the present study, we evaluated the effect of the noncompetitive low-affinity NMDA receptor antagonist N-(2-adamantyl)-hexamethyleneimine hydrochloride (hemantane) 15 , 16 in a topical formulation compared to the COX inhibitor diclofenac in a topical formulation in rats with T cell-dependent arthritis induced by Freund’s Complete Adjuvant (FCA).…”

Section: Introductionmentioning

confidence: 99%

Low-affinity NMDA receptor antagonist hemantane in a topical formulation attenuates arthritis induced by Freund’s Complete Adjuvant in rats

Ivanova¹,

Matyushkin²,

Sorokina³

et al. 2023

Adv Pharm Bull

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Objective: N-methyl-D-aspartate (NMDA) receptors that are expressed by T-cells modulate T-cell proliferation, cytotoxicity and cell migration toward chemokines. Several studies have shown an anti-inflammatory effect of NMDA receptor antagonists. This study compares the effect of the noncompetitive low-affinity NMDA receptor antagonist N-(2-adamantyl)-hexamethyleneimine hydrochloride (hemantane) in a topical formulation (gel) with the cyclooxygenase (COX) inhibitor diclofenac in a topical formulation (gel) in rats with arthritis induced by Freund’s Complete Adjuvant (FCA). Methods: On day 14 after an FCA injection into the left hind paw, rats with contralateral hind paw edema were selected for further investigation (29/65). They were treated with 5% Hemantane gel or 1% Diclofenac gel applied locally to hind paws daily for 2 weeks starting 14 days after the FCA injection. Rats with arthritis were examined hind paw edema, hyperalgesia, and motor deficits; their body weight and hematological parameters were recorded. The rats were euthanized on day 28, followed by histological examination of the ankle joint (HE stain). Results: Rats with arthritis exhibited hind paw inflammation and hyperalgesia, motor deficits, changes of hematological parameters, reduced weight gain and spleen hypertrophy. Histological examination of the ankle joint revealed degenerative-dystrophic lesions of the cartilaginous tissue, proliferative inflammation of the synovium, edema and lymphocytic/macrophage infiltration of periarticular tissues. Hemantane gel reduced hind paw edema, pain, motor deficits and histological signs of inflammation; its effect was comparable to diclofenac gel. Conclusion: Hemantane gel alleviates FCA-induced arthritis in rats, and its effect is comparable to diclofenac gel.

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Electric activity of the brain at early and late clinical stages of experimental modeling of Parkinson’s disease, an impact of hemantane

Voronina,

Kapitsa,

Kucheryanu

et al. 2024

S.S. Korsakov J. Neuro. Psych.

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Influence of Hemantane on Changes in Ca2+ and Na+ Caused by Activation of NMDA Channels in Cultured Rat Brain Neurons

Cited by 3 publications

References 19 publications

Synuclein Proteins in MPTP-Induced Death of Substantia Nigra Pars Compacta Dopaminergic Neurons

Synuclein Proteins in MPTP-Induced Death of Substantia Nigra Pars Compacta Dopaminergic Neurons

Low-affinity NMDA receptor antagonist hemantane in a topical formulation attenuates arthritis induced by Freund’s Complete Adjuvant in rats

Electric activity of the brain at early and late clinical stages of experimental modeling of Parkinson’s disease, an impact of hemantane

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