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

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.