Acta Anatomica Sinica

Acta Anatomica Sinica ›› 2023, Vol. 54 ›› Issue (6): 660-667.doi: 10.16098/j.issn.0529-1356.2023.06.006

• Neurobiology • Previous Articles     Next Articles

Nerve repair effect of olanzapine-mediated cyclic AMP response element binding protein/brain-derived neurotrophic factor/receptor tyrosine kinase receptors B pathway on schizophrenic rats

YAO  Su-hua1* YAN  Jun1  XIE  Fang1  LIN  Chun-hua2  HUANG  Zheng-chun3   

  1. 1.Ganzhou Third People’s Hospital Outpatient Department, Jiangxi Ganzhou 341000,China; 2.Department of Biochemistry, Biochemical Teaching and  Research Office of  Gannan Health Vocational College, Jiangxi Ganzhou 341000, China;  3.Department of Human Anatomy, Gannan Medical College, Jiangxi Ganzhou 341000, China

  • Received:2022-06-28 Revised:2022-09-30 Online:2023-12-06 Published:2023-12-06
  • Contact: YAO Su-hua E-mail:yaosuhuafg@163.com

PDF

Abstract:

Objective  To study the nerve repair effect of olanzapine on schizophrenia model rats through its effect on cyclic AMP response element binding protein（CREB）/brain-derived neurotrophic factor（BDNF）/receptor tyrosine kinase receptors B（TrkB）pathway.   Methods  Total 60 rats were divided into control group, model group, olanzapine low, middle and high dose group. The rats in the model group, olanzapine low, middle and high dose groups were injected intraperitoneally with MK-801［0.2 mg/(kg ·d)］, while the control injected with the same amount of normal saline. The low, middle and high dose olanzapine groups were perfused with olanzapine solution of 0.5 mg/(kg ·d),1.0 mg/(kg ·d) and 1.5mg/(kg ·d) respectively. The behavior of rats was scored according to ataxia and stereotyped behavior standards, cognitive function and learning ability were evaluated by Morris water maze test, serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were detected by ELISA method, hippocampal histopathology was observed under microscope, and apoptosis and expression of CREB/BDNF/TrkB pathway related proteins in hippocampus were detected.    Results  Compared with the control group, the ataxia, the score of stereotyped behavior, the expression of TNF-α, IL-6 and the rate of apoptosis in the model group increased significantly (P<0.01). Compared with the control group, the number of crossing the platform, the time of staying in the target quadrant and the relative expression of CREB, p-CREB, p-TrkB, TrkB and BDNF protein in the model group decreased significantly (P<0.01), and those in the low and middle dose olanzapine groups decreased significantly (P<0.05). Compared with the model group, the times of crossing the platform and the stay time in the target quadrant increased significantly in the low and middle dose olanzapine groups (P<0.05). In the model group and the low dose olanzapine group, the hippocampal cells were swollen obviously, the nucleus was broken and divided, pyknosis, and the tissue arrangement was disorderly, while the phenomenon of fragmentation and nuclear pyknosis was rarely seen in the middle and high dose olanzapine groups.   Conclusion  The nerve repair mechanism of olanzapine on schizophrenic model rats is related to improving cognitive impairment, protecting hippocampal neurons and activating the expression of CREB/BDNF/TrkB signal pathway in rats.

Key words: Olanzapine, Cyclic AMP response element binding protein/brain-derived neurotrophic factor/receptor tyrosine kinase receptors B pathway, Schizophrenia, Nerve regeneration, Enzyme-linked immunosorbent assay, Rat

CLC Number: