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Neuroprotective effects of insulin-like growth factor-2 in 6-hydroxydopamine-induced cellular and mouse models of Parkinson’s disease

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Neural Regeneration Research 2023年第5期18卷 1099-1106页

作者： Hai-Ying Zhang Yong-Cheng Jiang Jun-Rui Li Jia-Nan Yan Xin-Jue Wang Jia-Bing Shen Kai-Fu Ke Xiao-Su Gu Department of Neurology Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Research Center of Clinical Medicine Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Department of Clinical Medicine The First Clinical Medical College of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina

Skin-derived precursor Schwann cells have been reported to play a protective role in the central nervous system. The neuroprotective effects of skin-derived precursor Schwann cells may be attributable to the release of growth factors that nourish host cells. In this study, we first established a cellular model of Parkinson’s disease using 6-hydroxydopamine. When SH-SY5 Y cells were pretreated with conditioned medium from skin-derived precursor Schwann cells, their activity was greatly increased. The addition of insulin-like growth factor-2 neutralizing antibody markedly attenuated the neuroprotective effects of skin-derived precursor Schwann cells. We also found that insulin-like growth factor-2 levels in the peripheral blood were greatly increased in patients with Parkinson’s disease and in a mouse model of Parkinson’s disease. Next, we pretreated cell models of Parkinson’s disease with insulin-like growth factor-2 and administered insulin-like growth factor-2 intranasally to a mouse model of Parkinson’s disease induced by 6-hydroxydopamine and found that the level of tyrosine hydroxylase, a marker of dopamine neurons, was markedly restored, α-synuclein aggregation decreased, and insulin-like growth factor-2 receptor downregulation was alleviated. Finally, in vitro experiments showed that insulin-like growth factor-2 activated the phosphatidylinositol 3 kinase(PI3 K)/AKT pathway. These findings suggest that the neuroprotective effects of skin-derived precursor Schwann cells on the central nervous system were achieved through insulinlike growth factor-2, and that insulin-like growth factor-2 may play a neuroprotective role through the insulin-like growth factor-2 receptor/PI3 K/AKT pathway. Therefore, insulin-like growth factor-2 may be an useful target for Parkinson’s disease treatment.

关键词： 6-hydroxydopamine alpha-synuclein insulin-like growth factor-2 receptor insulin-like growth factor-2 neurodegeneration neuroprotection Parkinson’s disease skin-derived precursor Schwann cells

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Changes of Serum insulin-like growth factor-2 Response to Negative Symptom Improvements in Schizophrenia Patients Treated with Atypical Antipsychotics

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Current Medical Science 2020年第3期40卷 563-569页

作者： Xue-lin CHAO Shu-zhen JIANG Jian-wen XIONG Jin-qiong ZHAN Bo WEI Chun-nuan CHEN Yuan-jian YANG Department of Psychosomatic Medicine The First Affiliated Hospital of Nanchang UniversityNanchang330006China Biological Psychiatry Laboratory Jiangxi Mental Hospital/Affiliated Mental Hospital of Nanchang UniversityNanchang330029China Department of Psychiatry Jiangxi Mental Hospital/Affiliated Mental Hospital of Nanchang UniversityNanchang330029China Department of Neurology The Second Clinical Medical CollegeThe Second Affiliated HospitalFujian Medical UniversityQuanzhou362000China

Accumulating evidence suggests that a disruption of early brain development,in which insulin-like growth factor-2(IGF-2)has a crucial role,may underlie the pathophysiology of schizophrenia.Our previous study has shown that decreased serum IGF-2 was correlated with the severity of psychopathology in patients with schizophrenia.Here we conducted a prospective observation trial to investigate the effects of atypical antipsychotics on serum IGF-2 level and its relationship with clinical improvements in schizophrenia patients.Thirty-one schizophrenia patients with acute exacerbation and 30 healthy individuals were recruited in this study.Psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale(PANSS)and serum IGF-2 levels were determined using ELISA.We found that schizophrenia patients with acute exacerbation had lower serum IGF-2 levels than control individuals at baseline(P2 months of atypical antipsychotic treatment,a significant improvement in each PANSS subscore and total score was observed in patients(all P2 levels of patients were significantly increased compared with those at baseline(203.13±64.62 vs.426.99±124.26 ng/mL;t=−5.044,P2 levels in patients were significantly correlated with the improvements of negative symptoms(r=−0.522,P=0.006).Collectively,our findings demonstrated changes of serum IGF-2 response to improvements of negative symptoms in schizophrenia patients treated with atypical antipsychotics,suggesting that serum IGF-2 might be a treatment biomarker for schizophrenia.

关键词： schizophrenia atypical antipsychotic insulin-like growth factor-2 negative symptoms

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Non-islet cell tumor hypoglycemia as an initial presentation of hepatocellular carcinoma coupled with end-stage liver cirrhosis: A case report and review of literature

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World Journal of Hepatology 2020年第8期12卷 519-524页

作者： Bo Yu Rana Douli Jose Amaya Suarez Victor Perez Gutierrez Mohammad Aldiabat Maria Khan Department of Medicine Lincoln Medical CenterBronxNY 10451-5504United States

BACKGROUND Non-islet cell tumor hypoglycemia(NICTH)is a rare cause of persistent hypoglycemia seen in patients with hepatocellular carcinoma(HCC).It is likely to be underdiagnosed especially in the patients with poor hepatic function and malnutrition.Herein,we report a rare case of NICTH as the initial presentation of HCC in a patient with chronic hypoglycemia due to end-stage liver cirrhosis.CASE SUMMARY A 62-year-old male with chronic fasting hypoglycemia secondary to end-stage hepatitis C-related cirrhosis,presented with altered mental status and dizziness.He was found to have severe hypoglycemia refractory to glucose supplements.Imaging studies and biopsy discovered well differentiated HCC without metastasis.Further evaluation showed low insulin,C-peptide and betahydroxybutyrate along with a high insulin-like growth factor-2/insulin-like growth factor ratio,consistent with the diagnosis of NICTH.As patient was not a candidate for surgical resection or chemotherapy,he was started on prednisolone with some improvements in the glucose homeostasis,but soon decompensated after a superimposed hospital acquired pneumonia.CONCLUSION NICTH can occur as the sole initial presentation of HCC and is often difficult to correct without tumor removal.Clinicians should maintain high clinical suspicion for early recognition of paraneoplastic NICTH in patients at risk for HCC,even those with chronic fasting hypoglycemia in the setting of severe hepatic failure and malnutrition.

关键词： Non-islet cell tumor hypoglycemia Hepatocellular carcinoma Liver cirrhosis insulin-like growth factor-2 Paraneoplastic syndrome Case report

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