Modulation of neurosecretion and approaches for its multistep analysis

Kasatkina, L.A.; Gumenyuk, Vitaliy; Sturm, Eva; Heinemann, Ákos; Bernaś, Tytus; Тrikash, I. O.

doi:10.1016/j.bbagen.2018.08.004

Cited by 7 publications

(6 citation statements)

References 43 publications

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“…With this in mind, we studied the content of total cholesterol in synaptic membranes isolated from the cerebral hemispheres and found an increase in its level in prednisolone-supplemented animals (0.81 ± 0.07 µmol/mg protein) compared to the control level (0.65 ± 0.05 µmol/mg protein) (Figure 6D). Elevated synaptic plasma membrane cholesterol may indicate abnormal cholesterol metabolism associated with the administration of prednisolone and is comparable to that observed in alimentary vitamin D deficiency (Kasatkina et al, 2018). After supplementation with VD 3 , we observed an increase in mean amplitude of 103.07% compared with the prednisolone group (Tukey's test, p = 0.00002, Figure 6B), which almost reached the level of control values.…”

Section: Assessment Of Synaptic Function After Prednisolone Administr...supporting

confidence: 76%

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Brain vitamin D3-auto/paracrine system in relation to structural, neurophysiological, and behavioral disturbances associated with glucocorticoid-induced neurotoxicity

Lisakovska

Labudzynskyi

Khomenko

et al. 2023

Front. Cell. Neurosci.

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IntroductionVitamin D3 (VD3) is a potent para/autocrine regulator and neurosteroid that can strongly influence nerve cell function and counteract the negative effects of glucocorticoid (GC) therapy. The aim of the study was to reveal the relationship between VD3 status and behavioral, structural-functional and molecular changes associated with GC-induced neurotoxicity.MethodsFemale Wistar rats received synthetic GC prednisolone (5 mg/kg b.w.) with or without VD3 (1000 IU/kg b.w.) for 30 days. Behavioral, histological, physiological, biochemical, molecular biological (RT-PCR, Western blotting) methods, and ELISA were used.Results and discussionThere was no difference in open field test (OFT), while forced swim test (FST) showed an increase in immobility time and a decrease in active behavior in prednisolone-treated rats, indicative of depressive changes. GC increased the perikaryon area, enlarged the size of the nuclei, and caused a slight reduction of cell density in CA1-CA3 hippocampal sections. We established a GC-induced decrease in the long-term potentiation (LTP) in CA1-CA3 hippocampal synapses, the amplitude of high K+-stimulated exocytosis, and the rate of Ca2+-dependent fusion of synaptic vesicles with synaptic plasma membranes. These changes were accompanied by an increase in nitration and poly(ADP)-ribosylation of cerebral proteins, suggesting the development of oxidative-nitrosative stress. Prednisolone upregulated the expression and phosphorylation of NF-κB p65 subunit at Ser311, whereas downregulating IκB. GC loading depleted the circulating pool of 25OHD3 in serum and CSF, elevated VDR mRNA and protein levels but had an inhibitory effect on CYP24A1 and VDBP expression. Vitamin D3 supplementation had an antidepressant-like effect, decreasing the immobility time and stimulating active behavior. VD3 caused a decrease in the size of the perikaryon and nucleus in CA1 hippocampal area. We found a recovery in depolarization-induced fusion of synaptic vesicles and long-term synaptic plasticity after VD3 treatment. VD3 diminished the intensity of oxidative-nitrosative stress, and suppressed the NF-κB activation. Its ameliorative effect on GC-induced neuroanatomical and behavioral abnormalities was accompanied by the 25OHD3 repletion and partial restoration of the VD3-auto/paracrine system.ConclusionGC-induced neurotoxicity and behavioral disturbances are associated with increased oxidative-nitrosative stress and impairments of VD3 metabolism. Thus, VD3 can be effective in preventing structural and functional abnormalities in the brain and behavior changes caused by long-term GC administration.

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Section: Assessment Of Synaptic Function After Prednisolone Administr...supporting

confidence: 76%

“…Purified synaptosomes were obtained from Wistar rat brains by the differential centrifugation ( Kasatkina et al, 2018 ) using Ficoll-400 density gradient centrifugation of crude samples. Synaptosomes were used within 2–4 h after isolation.…”

Section: Methodsmentioning

confidence: 99%

Brain vitamin D3-auto/paracrine system in relation to structural, neurophysiological, and behavioral disturbances associated with glucocorticoid-induced neurotoxicity

Lisakovska

Labudzynskyi

Khomenko

et al. 2023

Front. Cell. Neurosci.

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“…This decreases the Ca 2+ influx into the presynaptic terminal, lowers the probability of Ca 2+ -dependent fusion of synaptic vesicles and attenuates the presynaptic neurotransmitter release. Synaptic vesicle recycling is a highly dynamic multistep process mediated by SNARE-proteins and other regulatory proteins, with Ca 2+ influx being a key factor for docked and primed synaptic vesicles to enter the fusion step [ 102 ]. Together with the activity-dependent production of eCBs and activation of CB 1 , presynaptic activity is essential for this type of plasticity as it determines the afferents in which eCB-LTD will be induced [ 103 ].…”

Section: The Role Of Retrograde Endocannabinoid Signaling In the Tuning Of Synaptic Strengthmentioning

confidence: 99%

Neuroprotective and Immunomodulatory Action of the Endocannabinoid System under Neuroinflammation

Kasatkina

Rittchen

Sturm

2021

IJMS

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Endocannabinoids (eCBs) are lipid-based retrograde messengers with a relatively short half-life that are produced endogenously and, upon binding to the primary cannabinoid receptors CB1/2, mediate multiple mechanisms of intercellular communication within the body. Endocannabinoid signaling is implicated in brain development, memory formation, learning, mood, anxiety, depression, feeding behavior, analgesia, and drug addiction. It is now recognized that the endocannabinoid system mediates not only neuronal communications but also governs the crosstalk between neurons, glia, and immune cells, and thus represents an important player within the neuroimmune interface. Generation of primary endocannabinoids is accompanied by the production of their congeners, the N-acylethanolamines (NAEs), which together with N-acylneurotransmitters, lipoamino acids and primary fatty acid amides comprise expanded endocannabinoid/endovanilloid signaling systems. Most of these compounds do not bind CB1/2, but signal via several other pathways involving the transient receptor potential cation channel subfamily V member 1 (TRPV1), peroxisome proliferator-activated receptor (PPAR)-α and non-cannabinoid G-protein coupled receptors (GPRs) to mediate anti-inflammatory, immunomodulatory and neuroprotective activities. In vivo generation of the cannabinoid compounds is triggered by physiological and pathological stimuli and, specifically in the brain, mediates fine regulation of synaptic strength, neuroprotection, and resolution of neuroinflammation. Here, we review the role of the endocannabinoid system in intrinsic neuroprotective mechanisms and its therapeutic potential for the treatment of neuroinflammation and associated synaptopathy.

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“…For Lev treatment protocol, rats were randomly distributed into two groups, 6 animals in each. Experimental group obtained Lev (60 mg/kg) per os once a day (Kasatkina et al, 2018). Control group received equivalent volume (100 μl) of vehicle (distilled water).…”

Section: Animalsmentioning

confidence: 99%

“…The R18 assay is based on the changes of fluorescence intensity upon fusion of R18-labeled SVs and unlabeled PMs. SVs were labeled with R18 (20 μM) as described earlier (Kasatkina et al, 2018) and preincubated with vehicle, 75 nM nicotine or 30 nM PNU282987 for 10 min at 37°C. These SVs (3 μl) were mixed with unlabeled PMs (1:9, based on protein concentration) in the medium of cytosolic synaptic proteins and supplemented with 10 −5 M Ca 2+ (start point, Trikash et al, 2010).…”

Section: R18 Assay For Monitoring the Membrane Fusionmentioning

confidence: 99%

Nicotinic acetylcholine receptors regulate clustering, fusion and acidification of the rat brain synaptic vesicles

Тrikash

Kasatkina

Lykhmus

et al. 2020

Neurochemistry International

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The brain nicotinic acetylcholine receptors (nAChRs) expressed in pre-synaptic nerve terminals regulate neurotransmitter release. However, there is no evidence for the expression of nAChRs in synaptic vesicles, which deliver neurotransmitter to synaptic cleft. The aim of this paper was to investigate the presence of nAChRs in synaptic vesicles purified from the rat brain and to study their possible involvement in vesicles life cycle. According to dynamic light scattering analysis, the antibody against extracellular domain (1-208) of α7 nAChR subunit inhibited synaptic vesicles clustering. Sandwich ELISA with nAChR subunit-specific antibodies demonstrated the presence of α4β2, α7 and α7β2nAChR subtypes in synaptic vesicles and showed that α7 and β2 nAChR subunits are co-localized with synaptic vesicle glycoprotein 2A (SV2A). Pre-incubation with either α7selective agonist PNU282987 or nicotine did not affect synaptic vesicles clustering but delayed their Ca 2+dependent fusion with the plasma membranes. In contrast, nicotine but not PNU282987 stimulated acidification of isolated synaptic vesicles, indicating that α4β2 but not α7-containing nAChRs are involved in regulation of proton influx and neurotransmitter refilling. Treatment of rats with levetiracetam, a specific modulator of SV2A, increased the content of α7 nAChRs in synaptic vesicles accompanied by increased clustering but decreased Ca 2+-dependent fusion. These data for the first time demonstrate the presence of nAChRs in synaptic vesicles and suggest an active involvement of cholinergic regulation in neurotransmitter release. Synaptic vesicles may be an additional target of nicotine inhaled upon smoking and of α7-specific drugs widely discussed as antiinflammatory and pro-cognitive tools.

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Modulation of neurosecretion and approaches for its multistep analysis

Cited by 7 publications

References 43 publications

Brain vitamin D3-auto/paracrine system in relation to structural, neurophysiological, and behavioral disturbances associated with glucocorticoid-induced neurotoxicity

Brain vitamin D3-auto/paracrine system in relation to structural, neurophysiological, and behavioral disturbances associated with glucocorticoid-induced neurotoxicity

Neuroprotective and Immunomodulatory Action of the Endocannabinoid System under Neuroinflammation

Nicotinic acetylcholine receptors regulate clustering, fusion and acidification of the rat brain synaptic vesicles

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