Streptozotocin Impairs Proliferation and Differentiation of Adult Hippocampal Neural Stem Cells in Vitro-Correlation With Alterations in the Expression of Proteins Associated With the Insulin System

Park, Sun; Ortega, Guillermo J.; Tan, Yan Ming; Hua, Qian; Riederer, Peter; Deckert, Jürgen; Schmitt-Böhrer, Angelika G.

doi:10.3389/fnagi.2018.00145

Cited by 29 publications

(23 citation statements)

References 103 publications

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“…42 A close relationship exists between impairment in behavioral function and disruption of neurotransmitters homeostasis in hippocampus in AD as well as in experimental animals. 43,44 Linked with this, these alterations in hippocampal neurochemistry following ICV-STZ infusion in rats in the present study. On the other hand, significant alterations in hippocampal neurochemistry including deficits in monoamines (NE, DA and 5HT) and disturbed balance of GABA and Glutamate have also been reported to occur in AD 45,46 as well as following ICV-STZ infusion in rats.…”

Section: Discussionsupporting

confidence: 69%

Chebulinic Acid Negated the Development of Streptozotocin- Induced Experimental Dementia in Rats

Rimpi

Deshmukh

2020

IJPI

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Background: With the constant failure of the clinical trials and continuous exploration of a therapeutic target against Alzheimer's disease (AD) is the utmost needed. Chebulinic acid (ChA) has been reported to possess neuroprotective potential in various neurodegenerative models such as anxiety and depression. Materials and Methods: In the current study, the ChA was challenged on the progression of AD induced by intracerebroventricular (ICV)-streptozotocin (STZ)-induced neurotoxicity to determine its therapeutic potential in experimental dementia. STZ was infused bilaterally (3 mg/kg/icv) on day 1 st and 3 rd after surgery. ChA (25, 50 and 100 mg/kg/p.o) was administered from 7 th day onwards up to 21 st day following 1 st ICV-STZ infusion. Cognitive impairment was evaluated by actophotometer, Morris water maze (MWM) and object recognition task (ORT) in rats whereas biochemical, neurochemical, neuroinflammatory were evaluated using hipoocampal brain regions on day 22 nd. Results: Ventricular administration of STZ in rats found to significantly shorten the latency time on the MWM and ORT which was associated with significant alterations in hippocampal biochemistry, including elevation in oxidative stress and compromised antioxidant defense, neurotransmitter alteration and elevation in neuroinflammatory cytokine levels. ChA treatment significantly prevented the ICV-STZ-induced memory deficit by attenuating the hippocampal neuronal loss, neuroinflammation and compromised antioxidant defense and cholinergic deficits in rats. Conclusion: These results clearly pointed to the pivotal role of ChA in ICV-STZ induced neurotoxicity and its association may be a promising alternative to be investigated in the treatment of AD-like dementia.

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Section: Discussionsupporting

confidence: 69%

Chebulinic Acid Negated the Development of Streptozotocin- Induced Experimental Dementia in Rats

Rimpi

Deshmukh

2020

IJPI

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“…Streptozotocin (STZ) is a glucosamine-nitrosourea diabetogenic agent used to generate T1DM in rodents based on its preferential uptake into pancreatic beta cells via Glut2 transporters, nuclear entry, alkylation of DNA, and beta cell death 73 . At low doses, STZ can induce T2DM and insulin resistance in the CNS following intracerebroventricular administration 74,75 . Insulin and IGF-1 resistance in human T2DM significantly increases the risk of AD 71,76 .…”

Section: T2dm Is a Risk Factor For Admentioning

confidence: 99%

The Continuing Evolution of Insulin-like Growth Factor Signaling

Rosenzweig

2020

F1000Res

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The insulin-like growth factors (IGFs; IGF1/IGF2), known for their regulation of cell and organismal growth and development, are evolutionarily conserved ligands with equivalent peptides present in flies (D. melanogaster), worms (C. elegans) among others. Two receptor tyrosine kinases, the IGF1 receptor and the insulin receptor mediate the actions of these ligands with a family of IGF binding proteins serving as selective inhibitors of IGF1/2. This treatise reviews recent findings on IGF signaling in cancer biology and central nervous system function. This includes overexpression of IGF1 receptors in enhancing tumorigenesis, acquired resistance and contributions to metastasis in multiple cancer types. There is accumulating evidence that insulin resistance, a hallmark of type 2 diabetes, occurs in the central nervous system, independent of systemic insulin resistance and characterized by reduced insulin and IGF1 receptor signaling, and may contribute to dementias including Alzheimer’s Disease and cognitive impairment. Controversy over the role(s) of IGF signaling in cancer and whether its inhibition would be of benefit, still persist and extend to IGF1’s role in longevity and central nervous system function.

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“…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%

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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Streptozotocin Impairs Proliferation and Differentiation of Adult Hippocampal Neural Stem Cells in Vitro-Correlation With Alterations in the Expression of Proteins Associated With the Insulin System

Cited by 29 publications

References 103 publications

Chebulinic Acid Negated the Development of Streptozotocin- Induced Experimental Dementia in Rats

Chebulinic Acid Negated the Development of Streptozotocin- Induced Experimental Dementia in Rats

The Continuing Evolution of Insulin-like Growth Factor Signaling

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

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