Catalpol Enhances Neurogenesis And Inhibits Apoptosis Of New Neurons Via BDNF, But Not The BDNF/Trkb Pathway

• Published in: Drug design, development and therapy Vol. 13; pp. 4145 - 4157
• Main Authors: Zhu, Hui-Feng, Shao, Yali, Qin, Lei, Wang, Jing-Huan, Feng, Shan, Jiang, Yun-Bin, Wan, Dong
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.12.2019; Taylor & Francis Ltd; Dove; Dove Medical Press
• Subjects: Angiogenesis; Animals; Apoptosis; Apoptosis - drug effects; BAX protein; Bcl-2 protein; Brain; brain derived neurotrophic factor (bdnf); Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Caspase-3; catalpol; Cerebral blood flow; Cerebral infarction; Dose-Response Relationship, Drug; Infarction; Iridoid Glucosides - administration & dosage; Iridoid Glucosides - pharmacology; Ischemia; Laboratory animals; Male; Medical research; Molecular Structure; Nestin; Neurogenesis; Neurogenesis - drug effects; Neurological diseases; neurological function; Neurons; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Newborn infants; Occlusion; Original Research; permanent occlusion of the middle cerebral artery (pmcao); Pharmacology; Phosphorylase; Phosphorylases; Physiology; Rats; Rats, Sprague-Dawley; Receptor, trkB - metabolism; Signal Transduction - drug effects; Software; Stem cells; Stroke; Structure-Activity Relationship; Subgroups; Survival; TrkB receptors; Variance analysis; Vascular endothelial growth factor; China; United States > US; Germany; catalpol; brain derived neurotrophic factor; neurological function; BDNF; neurogenesis; pMCAO; permanent middle cerebral artery occlusion
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S223322

The role of catalpol in brain neurogenesis and newborn neuron survival has not been previously determined in permanent middle cerebral artery occlusion (pMCAO). Fifty-four rats were divided into 6 groups: pMCAO (model, n=9); sham operation (NS, n=9); catalpol treatment (5 mg/kg and 10 mg/kg subgroups, n=9 each); K252a (n=9); and K252a+catalpol 5 mg/kg (n=9) with stroke. The effects of catalpol on behavior, neurogenesis surrounding the infarction ipsilateral to pMCAO, and the expression of brain-derived neurotrophic factor (BDNF) and its receptor (TrkB) were evaluated. Vehicle or, K252a (i.p.), an inhibitor of TrkB phosphorylase. Repeated administration of catalpol reduced neurological deficits and significantly improved neurogenesis. Catalpol increased the number of newborn immature neurons, as determined by BrdU -Nestin and BrdU -Tuj-1 staining, and downregulated cleaved caspase 3 in Tuj-1 cells at day 7 following stroke. Moreover, catalpol increased the protein expression of Tuj-1, MAP2, and the Bcl-2/Bax ratio, as determined using Western blot. Catalpol also significantly increased brain levels of BDNF, but not TrkB, resulting in enhanced survival of newborn neurons via inhibition of apoptosis. Catalpol may contribute to neurogenesis in infarcted brain regions and help promote the survival of newborn neurons by activating BDNF, but not BDNF/TrkB signaling.