Brain-Derived Neurotrophic Factor Delivered Intranasally Relieves Post-Traumatic Stress Disorder Symptoms Caused by a Single Prolonged Stress in Rats.

IF 2.3 4区心理学 Q3 NEUROSCIENCES

Neuropsychobiology Pub Date : 2023-01-01 DOI:10.1159/000528755

Leile Zhang, Lisha Deng, Chaofeng Ma, Hui Zhang, Yonghui Dang

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引用次数: 1

Abstract

Introduction: In our previous study, we successfully constructed the recombinant brain-derived neurotrophic factor (BDNF)-adeno-associated virus (AAV) modified by the influenza virus hemagglutinin-2 (HA2) and trans-transcriptional activator (TAT). BDNF-HA2TAT/AAV has been confirmed to have antidepression effects. BDNF-HA2TAT/AAV seems a promising therapy for post-traumatic stress disorder (PTSD) as the BDNF plays an important role in the function of the nervous system. However, the effects of BDNF-HA2TAT/AAV on PTSD caused by the single prolonged stress (SPS) model are unknown.

Methods: After the SPS model was established, BDNF-HA2TAT/AAV was administered (1 × 1011 vg per rat) through inhalation in the SPS + BDNF group for 2 weeks. Next, the rats underwent behavioral tests including an open-field test (OFT), elevated plus maze (EPM), and a forced swimming test (FST). Sera and hippocampi were obtained from the rats, and an enzyme-linked immune sorbent assay was performed to determine corticosterone concentration. Western blotting was conducted to determine BDNF, tyrosine kinase receptor B (TrkB), cAMP-response element-binding protein, and protein kinase B levels.

Results: BDNF-HA2TAT/AAV released anxiety-like and depression-like behaviors in OFT, EPM, and FST. BDNF-HA2TAT/AAV also results in high plasma concentrations of corticosterone, BDNF, and TrkB in the hippocampus.

Conclusions: SPS is an excellent animal model to assess PTSD. BDNF-HA2TAT/AAV therapeutically effects PTSD caused by SPS, with changes seen in plasma corticosterone and BDNF-TrkB pathways within the hippocampus; therefore, BDNF-HA2TAT/AAV may be a promising treatment for patients with PTSD.

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鼻内给予脑源性神经营养因子缓解大鼠单次长期应激引起的创伤后应激障碍症状。

在我们之前的研究中，我们成功构建了由流感病毒血凝素-2 (HA2)和反转录激活剂(TAT)修饰的重组脑源性神经营养因子(BDNF)-腺相关病毒(AAV)。BDNF-HA2TAT/AAV已被证实具有抗抑郁作用。BDNF- ha2tat /AAV是治疗创伤后应激障碍(PTSD)的一种很有前景的疗法，因为BDNF在神经系统功能中起着重要作用。然而，BDNF-HA2TAT/AAV对单一延长应激(SPS)模型所致PTSD的影响尚不清楚。方法:SPS模型建立后，SPS + BDNF组吸入BDNF- ha2tat /AAV (1 × 1011 vg /只大鼠)2周。接下来，大鼠进行了行为学测试，包括开放场测试(OFT)、升高加迷宫(EPM)和强迫游泳测试(FST)。取大鼠血清和海马，采用酶联免疫吸附法测定皮质酮浓度。Western blotting检测BDNF、酪氨酸激酶受体B (TrkB)、camp反应元件结合蛋白和蛋白激酶B水平。结果:BDNF-HA2TAT/AAV在OFT、EPM和FST中释放焦虑样和抑郁样行为。BDNF- ha2tat /AAV也导致海马皮质酮、BDNF和TrkB血浆浓度升高。结论:SPS是评估创伤后应激障碍的良好动物模型。BDNF-HA2TAT/AAV通过改变血浆皮质酮和海马内BDNF-TrkB通路对SPS引起的PTSD具有治疗作用;因此，BDNF-HA2TAT/AAV可能是治疗PTSD患者的一种很有前景的方法。

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来源期刊

Neuropsychobiology 医学-精神病学

CiteScore

7.20

自引率

0.00%

发文量

审稿时长

6 months

期刊介绍： The biological approach to mental disorders continues to yield innovative findings of clinical importance, particularly if methodologies are combined. This journal collects high quality empirical studies from various experimental and clinical approaches in the fields of Biological Psychiatry, Biological Psychology and Neuropsychology. It features original, clinical and basic research in the fields of neurophysiology and functional imaging, neuropharmacology and neurochemistry, neuroendocrinology and neuroimmunology, genetics and their relationships with normal psychology and psychopathology. In addition, the reader will find studies on animal models of mental disorders and therapeutic interventions, and pharmacoelectroencephalographic studies. Regular reviews report new methodologic approaches, and selected case reports provide hints for future research. ''Neuropsychobiology'' is a complete record of strategies and methodologies employed to study the biological basis of mental functions including their interactions with psychological and social factors.