Neuroprotective role of an N-acetyl serotonin derivative via activation of tropomyosin-related kinase receptor B after subarachnoid hemorrhage in a rat model

Junjia Tang; Qin Hu; Yujie Chen; Fei Liu; Yun Zheng; Jiping Tang; Jianmin Zhang; John H. Zhang

Neurobiology of Disease (Jun 2015)

Neuroprotective role of an N-acetyl serotonin derivative via activation of tropomyosin-related kinase receptor B after subarachnoid hemorrhage in a rat model

Junjia Tang,
Qin Hu,
Yujie Chen,
Fei Liu,
Yun Zheng,
Jiping Tang,
Jianmin Zhang,
John H. Zhang

Affiliations

Junjia Tang: Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Departments of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA
Qin Hu: Departments of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA
Yujie Chen: Departments of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA
Fei Liu: Departments of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA
Yun Zheng: Departments of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA
Jiping Tang: Departments of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA
Jianmin Zhang: Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Correspondence to: J. Zhang, Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China. Fax: +86 571 87784755.
John H. Zhang: Departments of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA; Correspondence to: J.H. Zhang, Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA 92354, USA. Fax: +1 909 5580119.

Journal volume & issue: Vol. 78
pp. 126 – 133

Abstract

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N-[2-(5-hydroxy-1H-indol-3-yl) ethyl]-2-oxopiperidine-3-carboxamide (HIOC), an N-acetyl serotonin derivative, selectively activates tropomyosin-related kinase receptor B (TrkB). This study is to investigate a potential role of HIOC on ameliorating early brain injury after experimental subarachnoid hemorrhage (SAH). One hundred and fifty-six adult male Sprague–Dawley rats were used. SAH model was induced by endovascular perforation. TrkB small interfering RNA (siRNA) or scramble siRNA was injected intracerebroventricularly 24 h before SAH. HIOC was administrated intracerebroventricularly 3 h after SAH and compared with brain-derived neurotrophic factor (BDNF). SAH grade and neurologic scores were evaluated for the outcome study. For the mechanism study, the expression of TrkB, phosphorylated TrkB (p-TrkB), phosphorylated extracellular signal regulated kinase (p-ERK), B-cell lymphoma 2 (Bcl-2) and cleaved caspase 3 (CC3) was detected by Western blots, and neuronal injury was determined by double immunofluorescence staining of neuronal nuclei and terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end-labeling. Knocking down of TrkB decreased the expression of Bcl-2 and aggravated neurologic deficits 24 h after SAH. HIOC activated TrkB/ERK pathway, decreased neuronal cell death, and improved neurobehavioral outcome, and these effects were abolished by TrkB siRNA. HIOC was more potent than BDNF in reduction of apoptosis 24 h post-SAH. Thus, we conclude that administration of HIOC activated TrkB/ERK signaling cascade and attenuated early brain injury after SAH. HIOC may be a promising agent for further treatment for SAH and other stroke events.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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