Streptozotocin toxicity in vitro depends on maturity of neurons

Isaev, N. K.; Генрихс, Е. Е.; Воронков, Д. Н.; Kapkaeva, Marina R.; Stelmashook, E. V.

doi:10.1016/j.taap.2018.04.024

Cited by 18 publications

(8 citation statements)

References 31 publications

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“…In primary cell cultures, however, slightly higher concentrations of STZ were found to exert similar damage. In rat cerebellar granule cells, significant cell damage was induced by 2.5-4.5 mM (Genrikhs et al 2017) and 3-4 mM STZ (Isaev et al 2018), while the proliferation of adult hippocampal neural stem cells (NSCs) was inhibited by 2.5 mM STZ (Sun et al 2018). These concentrations correspond well to the 4 Insulin dose and time dependently improved plasma membrane integrity in LS-and 1 mM STZ-treated cells.…”

Section: Discussionmentioning

confidence: 68%

“…STZ is also used in in vitro experiments aiming at modeling cellular processes characteristic for Alzheimer's disease and its potential therapeutic measures (Plaschke and Kopitz 2015;Rajasekar et al 2016;Guo et al 2016). STZ exerted dose-dependent cytotoxicity on several neuronal cell types (Plaschke and Kopitz 2015;Isaev et al 2018;Genrikhs et al 2017) leading to depolarization of mitochondrial membrane (Genrikhs et al 2017;Biswas et al 2017), oxidative stress (Rajasekar et al 2014), increased apoptosis (Rajasekar et al 2014;Biswas et al 2016Biswas et al , 2017, increased tau protein phosphorylation (Biswas et al 2016), decreased glucose uptake (Biswas et al 2016(Biswas et al , 2017 and expression of GLUTs (Biswas et al 2017;Sun et al 2018), reduced expression of insulin receptor substrate-1 (IRS-1) (Wang et al 2011), and decreased levels of phosphorylated GSK-3 (Plaschke and Kopitz 2015;Rajasekar et al 2014). The protective effect of insulin against STZ-induced impaired cell viability was observed as well (Genrikhs et al 2017;Rajasekar et al 2014).…”

Section: Introductionmentioning

confidence: 99%

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Lack of insulin resistance in response to streptozotocin treatment in neuronal SH-SY5Y cell line

Bagaméry

Kecsmár

et al. 2019

J Neural Transm

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Recently, it is suggested that brain insulin resistance may contribute to the development of Alzheimer's disease; therefore, there is a high interest in its investigation. Streptozotocin (STZ) is often used to induce dysregulation of glucose and insulin metabolism in animal and cell culture models. Alteration in insulin sensitivity however, has not yet been assessed in neuronal cells after STZ treatment. We aimed at studying the concentration dependence of the protective effect of insulin on STZ-induced damage using SH-SY5Y cell line. Cells were treated with STZ and cell viability was assessed by resazurin reduction and lactate dehydrogenase release assays. Low serum (LS) medium was used as control damage. The effect of various concentrations (30, 100, 300, 1000 nM) of insulin was studied on cell viability and glycogen synthase kinase-3 (GSK-3) phosphorylation, an indicator of insulin signaling. STZ induced dose-and time-dependent cytotoxicity, its 1 mM concentration exerted a low, gradually developing damage. The cytoprotective effect of insulin was demonstrated in both STZ and LS groups. Its maximal effect was lower in the STZ-treated cells; however, its effective concentration remained largely unaltered. Insulin-induced GSK-3 phosphorylation was similar in the STZ-and LS-treated cells suggesting unchanged insulin signaling. Our present results indicate that STZ does not induce significant impairment in insulin sensitivity in SH-SY5Y cells, thus in this cell line it is not a good tool for studying the role of insulin resistance in neurodegeneration and to examine protective agents acting by improving insulin signaling.

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Section: Discussionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Lack of insulin resistance in response to streptozotocin treatment in neuronal SH-SY5Y cell line

Bagaméry

Kecsmár

et al. 2019

J Neural Transm

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“…Looking upward of the IR signalling to the level and synthesis of insulin in the rat brain, which was found to occur in neurons and not in glia (Schechter et al 1988), the earliest time-point of insulin mRNA assessment was 2 weeks following intracerebral STZ administration to young rat pups, in which decreased insulin gene expression was observed in the temporal lobe (Table 1). In adult rats, insulin mRNA expression in the hippocampus was found unchanged after 2 and 4 weeks, but was significantly decreased in periods > 1 month following STZ-icv treatment , which could be related to a lesser sensitivity of the mature neurons to STZ toxicity (Isaev et al 2018). Decreased insulin mRNA expression was also observed in different brain regions of monkeys, including the frontal cortex and hippocampus, 5 months following STZ-icv administration .…”

Section: Time Course Of the Appearance Of Insulin Signalling Dysfunctmentioning

confidence: 89%

Shared cerebral metabolic pathology in non-transgenic animal models of Alzheimer's and Parkinson's disease

et al. 2020

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Parkinson's disease (PD) and Alzheimer's disease (AD) are the most common chronic neurodegenerative disorders, characterized by motoric dysfunction or cognitive decline in the early stage, respectively, but often by both symptoms in the advanced stage. Among underlying molecular pathologies that PD and AD patients have in common, more attention is recently paid to the central metabolic dysfunction presented as insulin resistant brain state (IRBS) and altered cerebral glucose metabolism, both also explored in animal models of these diseases. This review aims to compare IRBS and alterations in cerebral glucose metabolism in representative non-transgenic animal PD and AD models. The comparison is based on the selectivity of the neurotoxins which cause experimental PD and AD, towards the cellular membrane and intracellular molecular targets as well as towards the selective neurons/non-neuronal cells, and the particular brain regions. Mitochondrial damage and coexpression of insulin receptors, glucose transporter-2 and dopamine transporter on the membrane of particular neurons as well as astrocytes seem to be the key points which are further discussed in a context of alterations in insulin signalling in the brain and its interaction with dopaminergic transmission, particularly regarding the time frame of the experimental AD/ PD pathology appearance and the correlation with cognitive and motor symptoms. Such a perspective provides evidence on IRBS being a common underlying metabolic pathology and a contributor to neurodegenerative processes in representative non-transgenic animal PD and AD models, instead of being a direct cause of a particular neurodegenerative disorder.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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“…В целом, учитывая, что танициты модулируют функции нейронов вентро-медиального, дорсо-медиального и аркуатного ядер гипоталамуса и вовлечены в механизмы регуляции как локального, так и системного энергетического обмена и в контроль пищевого поведения [15,18,29], их повреждение, вероятно, приводит к наблюдающимся на данной модели БА нарушениям углеводного обмена [30,31]. Вместе с тем, дисфункцию структур гипоталамуса при введении СТЗ и показанные ранее нейродегенеративные изменения в гипоталамусе на поздних сроках [31] [38], а также его высокой токсичностью по отношению к незрелым нейронам [39]. Поскольку танициты, по-видимому, имеют нейрогенный потенциал [40], нарушение пролиферации и гибель нейральных стволовых клеток гипоталамуса под действием СТЗ может иметь отсроченные эффекты, связанные с нарушением пластичности нейронных сетей гипоталамуса, контролирующих гомеостатические процессы.…”

Section: обсуждение результатовunclassified

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2021

Вестник РГМУ

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Вирусные механизмы доставки генетического материала широко используются в молекулярной медицине. Рекомбинантные аденоассоциированные вирусы (rAAV) представляют собой перспективный инструмент для доставки генов in vivo. В обзоре представлены нозологический спектр, молекулярные механизмы, выбор способа введения препарата в зависимости от структур-мишеней, выбор серотипа, а также методы производства активных ингредиентов для rAAV-опосредованной генной терапии.Viral mechanisms for the delivery of genetic material are widely used in molecular medicine. Recombinant adeno-associated viruses (rAAV) represent a promising tool for in vivo gene delivery. The review considers nosological spectrum, molecular mechanisms, the choice of drug administration route depending on target structures, the choice of serotype, and the methods of active ingredient manufacturing for rAAV-mediated gene therapy.

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Streptozotocin toxicity in vitro depends on maturity of neurons

Cited by 18 publications

References 31 publications

Lack of insulin resistance in response to streptozotocin treatment in neuronal SH-SY5Y cell line

Lack of insulin resistance in response to streptozotocin treatment in neuronal SH-SY5Y cell line

Shared cerebral metabolic pathology in non-transgenic animal models of Alzheimer's and Parkinson's disease

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