Increased BDNF protein expression after ischemic or PKC epsilon preconditioning promotes electrophysiologic changes that lead to neuroprotection

Jake T. Neumann, John W. Thompson, Ami Raval, Charles H. Cohan, Kevin B. Koronowski, Miguel Perez-Pinzon

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Ischemic preconditioning (IPC) via protein kinase C epsilon (PKCε) activation induces neuroprotection against lethal ischemia. Brain-derived neurotrophic factor (BDNF) is a pro-survival signaling molecule that modulates synaptic plasticity and neurogenesis. Interestingly, BDNF mRNA expression increases after IPC. In this study, we investigated whether IPC or pharmacological preconditioning (PKCε activation) promoted BDNF-induced neuroprotection, if neuroprotection by IPC or PKCε activation altered neuronal excitability, and whether these changes were BDNF-mediated. We used both in vitro (hippocampal organotypic cultures and cortical neuronal-glial cocultures) and in vivo (acute hippocampal slices 48 hours after preconditioning) models of IPC or PKCε activation. BDNF protein expression increased 24 to 48 hours after preconditioning, where inhibition of the BDNF Trk receptors abolished neuroprotection against oxygen and glucose deprivation (OGD) in vitro. In addition, there was a significant decrease in neuronal firing frequency and increase in threshold potential 48 hours after preconditioning in vivo, where this threshold modulation was dependent on BDNF activation of Trk receptors in excitatory cortical neurons. In addition, 48 hours after PKCε activation in vivo, the onset of anoxic depolarization during OGD was significantly delayed in hippocampal slices. Overall, these results suggest that after IPC or PKCε activation, there are BDNF-dependent electrophysiologic modifications that lead to neuroprotection.

Original languageEnglish
Pages (from-to)121-130
Number of pages10
JournalJournal of Cerebral Blood Flow and Metabolism
Volume35
Issue number1
DOIs
StatePublished - Jan 1 2015

Fingerprint

Protein Kinase C-epsilon
Brain-Derived Neurotrophic Factor
Nerve Growth Factors
Ischemic Preconditioning
trkB Receptor
Oxygen
Glucose
Neuronal Plasticity
Neurogenesis
Coculture Techniques
Neuroprotection
Neuroglia
Ischemia
Pharmacology
Neurons
Messenger RNA

Keywords

  • cell death
  • excitotoxicity
  • hyperpolarization
  • ischemic tolerance
  • Na channels
  • neurotrophins

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Neurology

Cite this

Increased BDNF protein expression after ischemic or PKC epsilon preconditioning promotes electrophysiologic changes that lead to neuroprotection. / Neumann, Jake T.; Thompson, John W.; Raval, Ami; Cohan, Charles H.; Koronowski, Kevin B.; Perez-Pinzon, Miguel.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 35, No. 1, 01.01.2015, p. 121-130.

Research output: Contribution to journalArticle

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