BDNF Mediates Neuroprotection against Oxygen-Glucose Deprivation by the Cardiac Glycoside Oleandrin

Abstract

We have previously shown that the botanical drug candidate PBI-05204, a supercritical CO 2 extract of Nerium oleander, provides neuroprotection in both in vitro and in vivo brain slice-based models for focal ischemia (Dunn et al., 2011). Intriguingly, plasma levels of the neurotrophin BDNF were increased in patients treated with PBI-05204 in a phase I clinical trial (Bidyasar et al., 2009). We thus tested the hypothesis that neuroprotection provided by PBI-05204 to rat brain slices damaged by oxygen-glucose deprivation (OGD) is mediated by BDNF. We found, in fact, that exogenous BDNF protein itself is sufficient to protect brain slices against OGD, whereas downstream activation of TrkB receptors for BDNF is necessary for neuroprotection provided by PBI-05204, using three independent methods. Finally, we provide evidence that oleandrin, the principal cardiac glycoside component of PBI-05204, can quantitatively account for regulation of BDNF at both the protein and transcriptional levels. Together, these findings support further investigation of cardiac glycosides in providing neuroprotection in the context of ischemic stroke.

The Seed of <i>Zizyphus jujuba</i> var. <i>spinosa</i> Attenuates Alzheimer’s Disease-Associated Hippocampal Synaptic Deficits through BDNF/TrkB Signaling

“…Various neuroprotective agents regulate the synthesis of BDNF. 24,25) Therefore, because EZJ increased BDNF level in the hippocampus, we tested whether transcription and translation are involved in the synaptoprotective effect of EZJ. HFS induced LTP in control slices, but not in Aβ-treated slices (control, 153±3, n=5, Fig.…”

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

“…Several studies have demonstrated that TrkB signaling plays a pivotal role in central nervous system diseases, such as neurodegeneration, psychiatric disorders and ischemia stroke (Castello et al, 2014; Pandya et al, 2014; Van Kanegan et al, 2014). Our previous study suggested that inhibition of protein tyrosine phosphatases could preserve TrkB activation, thus preventing early brain injury after SAH in rat model (Hasegawa et al, 2011a).…”

“…TrkB is the primary high affinity receptor for BDNF and BDNF-TrkB axis has been revealed to be neuroprotective involving in various central nervous system disorders, including ischemic injury (Han and Holtzman, 2000; Han et al, 2011; Muller et al, 2008; Van Kanegan et al, 2014), which made BDNF a promising agent for stroke treatment. Therefore, in the current study, we compared the therapeutic effects of HIOC with BDNF after SAH.…”

“…Phosphorylation of TrkB ameliorated brain injury in ischemic stroke models (Cui et al, 2013; Van Kanegan et al, 2014). Our previous study revealed that the brain-derived neurotrophic factor (BDNF)/TrkB signaling pathway was involved in apoptosis after SAH (Hasegawa et al, 2011a).…”

H&lt;sub&gt;2&lt;/sub&gt;S protects PC12 cells against toxicity of corticosterone by modulation of BDNF-TrkB pathway

“…Additionally, the levels of BDNF in hippocampus are reduced in corticosterone-induced mouse depression model [31]. Increasing data have shown that BDNF has neuroprotective activity [32][33][34]. BDNF is responsible for the structure and function of plasticity in the brain [35], prevents damages to neurons in the brain [36], and plays a key role in neural development and maintenance of the central and peripheral neurons [37].…”