Insulin-like growth factor reduced against decabromodiphenyl ether-209–induced neurodevelopmental toxicity in vivo and in vitro

2021 ◽  
pp. 096032712110459
Author(s):  
Yuanxiang Yang ◽  
Qianyun He ◽  
Zhengyu Zhang ◽  
Chunli Qi ◽  
Lina Ding ◽  
...  
Keyword(s):  
Growth Factor ◽  
Learning And Memory ◽  
Hippocampal Neurons ◽  
Morris Water Maze Test ◽  
Insulin Like Growth Factor ◽  
Protective Effects ◽  
Decabromodiphenyl Ether ◽  
Memory Ability ◽  
Neurodevelopmental Toxicity

Objective How to reduce the neurodevelopmental toxicity of decabromodiphenyl ether (PBDE-209) remains unclear. This study investigated neurodevelopmental toxicity of PBDE-209 and the protective effects of insulin-like growth factor-1 (IGF-1) Methods Pregnant Sprague–Dawley rats were treated with PBDE-209 and IGF-1, and the offspring were subjected to the Morris Water Maze test. Hippocampal neurons were cultured with PBDE-209 and IGF-1 or the PI3K inhibitor or MEK inhibitor for cell viability, apoptosis, immunofluorescence, and Western blot assays. Results Prenatal PBDE-209 exposure impaired the learning and memory ability of rats by delaying the mean latency to the platform compared, whereas prenatal treatment with IGF-1 treatment improved the learning and memory ability. In vitro, treatment of primary cultured hippocampal neural stem cells (H-NSCs) with PBDE-209 reduced cell proliferation and differentiation, but induced apoptosis. In contrast, IGF-1 treatment antagonized the cytotoxic effects of PBDE-209 in H-NSCs in vitro. At the gene level, IGF-1 inhibition of PBDE-209–induced cell cytotoxicity was through the activation of the PI3K/AKT and MEK/ERK signaling pathways in vitro because the effect of IGF-1 was blocked by the AKT inhibitor LY294002 and the ERK1/2 inhibitor PD98059. Conclusion Prenatal PBDE-209 exposure impaired the learning and memory ability of rats, whereas IGF-1 treatment was able to inhibit the neurodevelopmental toxicity of PBDE-209 by activation of the PI3K/AKT and ERK1/2 cell pathways.

scholarly journals Adulthood Deficiency of the Insulin-like Growth Factor-1 Receptor in Hippocampal Neurons Impairs Cell Structure and Spatial Learning and Memory in Male and Not Female Mice

2021 ◽  
Author(s):  
Cellas A Hayes ◽  
Erik L Hodges ◽  
Jessica P Marshall ◽  
Sreemathi Logan ◽  
Julie A Farley ◽  
...  
Keyword(s):  
Growth Factor ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Hippocampal Neurons ◽  
Spatial Learning And Memory ◽  
Insulin Like Growth Factor ◽  
Male Mice ◽  
Female Mice ◽  
Learning Impairments ◽  
Increased Risk

Reductions in insulin-like growth factor-1 (IGF-1) are associated with cognitive impairment and increased risk of neurodegenerative disease in advanced age. In mouse models, reduced IGF-1 early-in-life leads to memory impairments and synaptic dysfunction; however, these models are limited by systemic reductions in IGF-1. We hypothesized that IGF-1 continues to promote hippocampal neuron structure and function after development, and as such, the loss of IGF-1 signaling in adult neurons would lead to impaired spatial learning and memory. To test this, the IGF-1 receptor (IGF-1R) was genetically targeted in hippocampal neurons of adult male and female mice. Male mice deficient in neuronal IGF-1R exhibited spatial learning impairments as evidenced by increased pathlength and errors in the radial arm water maze. No differences in learning and memory were observed in female mice. Golgi-Cox staining revealed a reduced number of dendritic boutons of neurons the CA1 region of the hippocampus in male mice. Decreased MAPK and increased ROCK activity were also observed in these tissues. In vitro studies revealed that impaired neurite outgrowth due to inhibited IGF-1R signaling could be rescued by pharmacological inhibitors of ROCK. However, ROCK inhibition in neuronal IGF-1R deficient mice did not fully rescue learning impairments or bouton numbers. Together, our study highlights that IGF-1 continues to support spatial learning and memory and neuronal structure in adulthood.

scholarly journals The Protective and Restorative Effects of Growth Hormone and Insulin-Like Growth Factor-1 on Methadone-Induced Toxicity In Vitro

2018 ◽  
Vol 19 (11) ◽  
pp. 3627 ◽  
Author(s):  
Erik Nylander ◽  
Sofia Zelleroth ◽  
Fred Nyberg ◽  
Alfhild Grönbladh ◽  
Mathias Hallberg
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Cell Cultures ◽  
Mitochondrial Function ◽  
Membrane Integrity ◽  
Cortical Cell ◽  
Insulin Like Growth Factor ◽  
Protective Effects ◽  
Cortical Cells

Evidence to date suggests that opioids such as methadone may be associated with cognitive impairment. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are suggested to be neuroprotective and procognitive in the brain and may therefore counteract these effects. This study aims to explore the protective and restorative effects of GH and IGF-1 in methadone-treated cell cultures. Primary cortical cell cultures were harvested from rat fetuses and grown for seven days in vitro. To examine the protective effects, methadone was co-treated with or without GH or IGF-1 for three consecutive days. To examine the restorative effects, methadone was added for the first 24 h, washed, and later treated with GH or IGF-1 for 48 h. At the end of each experiment, mitochondrial function and membrane integrity were evaluated. The results revealed that GH had protective effects in the membrane integrity assay and that both GH and IGF-1 effectively recovered mitochondrial function and membrane integrity in cells pretreated with methadone. The overall conclusion of the present study is that GH, but not IGF-1, protects primary cortical cells against methadone-induced toxicity, and that both GH and IGF-1 have a restorative effect on cells pretreated with methadone.

scholarly journals GABAB receptor antagonist promotes hippocampal neurogenesis and facilitates cognitive function recovery following acute cerebral ischemia in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dan Song ◽  
Yaohua Chen ◽  
Cheng Chen ◽  
Lili Chen ◽  
Oumei Cheng
Keyword(s):  
Cognitive Function ◽  
Cerebral Ischemia ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Hippocampal Neurogenesis ◽  
Morris Water Maze Test ◽  
Spatial Learning And Memory ◽  
In Vitro Experiments ◽  
Adult Mice

Abstract Purpose and background Previous studies have suggested that promoting endogenous neurogenesis has great significance for the recovery of cognitive dysfunction caused by cerebral ischemia (CI). Pharmacological inhibition of GABAB receptor can enhance neurogenesis in adult healthy and depressed mice. In the study, we intended to investigate the effects of GABAB receptor antagonists on cognitive function and hippocampal neurogenesis in mice following CI. Methods Adult mice were subjected to bilateral common carotid artery occlusion (BCCAO) for 20 min to induce CI and treated with CGP52432 (antagonist of GABAB receptor, CGP, 10 mg/kg intraperitoneal injection) starting 24 h after CI. The Morris water maze test was performed to test spatial learning and memory at day 28. Immunofluorescence was applied to detect neurogenesis in the DG region at day 14 and 28. In in vitro experiments, cell proliferation was detected by CCK8 and immunofluorescence, and the expression of cAMP/CREB signaling pathway-related proteins was detected by ELISA assay and Western blot. Results CGP significantly improved spatial learning and memory disorders caused by CI, and it enhanced the proliferation of neural stem cells (NSCs), the number of immature neurons, and the differentiation from newborn cells to neurons. In vitro experiments further confirmed that CGP dose-dependently enhanced the cell viability of NSCs, and immunofluorescence staining showed that CGP promoted the proliferation of NSCs. In addition, treatment with CGP increased the expression of cAMP, PKA, and pCREB in cultured NSCs. Conclusion Inhibition of GABAB receptor can effectively promote hippocampal neurogenesis and improve spatial learning and memory in adult mice following CI.

Blended Effects of Herbal Components of Tokishakuyakusan on Somatomedin C/Insulin-like Growth Factor 1 Level in Rat Corpus Luteum

1991 ◽  
Vol 19 (01) ◽  
pp. 61-64 ◽  
Author(s):  
Satoshi Usuki
Keyword(s):  
Growth Factor ◽  
Corpus Luteum ◽  
Corpora Lutea ◽  
Insulin Like Growth Factor ◽  
Somatomedin C ◽  
Factor I ◽  
Peony Root ◽  
Growth Factor I ◽  
Herbal Components

The effect of herbal components of Tokishakuyakusan on somatomedin C/insulin-like growth factor I (IGF-1) level in medium from rat corpora lutea incubated in vitro was examined. Hoelen + peony root + Japanese angelica root, hoelen + peony root, hoelen + Japanese angelica root or peony root + Japanese angelica root decreased the IGF-1 level. The data suggest that constituent herbal components of Tokishakuyakusan regulate the IGF-1 level by rat corpora lutea.

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