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

Jake T Neumann; John W Thompson; Ami P Raval; Charles H Cohan; Kevin B Koronowski; Miguel A Perez-Pinzon

doi:10.1038/jcbfm.2014.185

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

Journal article

Open access

Peer reviewed

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

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

Journal of cerebral blood flow and metabolism, Vol.35(1), pp.121-130

2015-01

DOI: https://doi.org/10.1038/jcbfm.2014.185

PMCID: PMC4294405

PMID: 25370861

Abstract

Immunohistochemistry

Neurons - pathology

Neuroglia - pathology

Coculture Techniques

Humans

Brain Ischemia - metabolism

Male

Neuronal Plasticity - physiology

Cell Death

Neurons - physiology

Female

Brain-Derived Neurotrophic Factor - biosynthesis

Organ Culture Techniques

Neuroglia - physiology

Ischemic Preconditioning

Hippocampus - pathology

Rats, Sprague-Dawley

Blotting, Western

Action Potentials - physiology

Hippocampus - metabolism

Animals

Protein Kinase C-epsilon - metabolism

Brain Ischemia - pathology

Enzyme Activation

In Vitro Techniques

Ischemic preconditioning (IPC) via protein kinase C epsilon (PKCɛ) 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 (PKCɛ activation) promoted BDNF-induced neuroprotection, if neuroprotection by IPC or PKCɛ 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 PKCɛ 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 PKCɛ activation in vivo, the onset of anoxic depolarization during OGD was significantly delayed in hippocampal slices. Overall, these results suggest that after IPC or PKCɛ activation, there are BDNF-dependent electrophysiologic modifications that lead to neuroprotection.

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Citation topics: 1 Clinical & Life Sciences; 1.5 Neuroscience; 1.5.810 Nerve Growth Factor
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ESI research areas: Neuroscience & Behavior

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Title: Increased BDNF protein expression after ischemic or PKC epsilon preconditioning promotes electrophysiologic changes that lead to neuroprotection
Creators: Jake T Neumann - 1] Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA Evelyn F. McKnight Brain Institute, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA Department of Neurology, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA
John W Thompson - 1] Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA Department of Neurology, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA
Ami P Raval - 1] Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA Evelyn F. McKnight Brain Institute, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA Department of Neurology, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA
Charles H Cohan - 1] Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA Evelyn F. McKnight Brain Institute, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA Department of Neurology, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA
Kevin B Koronowski - 1] Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA Department of Neurology, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA
Miguel A Perez-Pinzon - 1] Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA Evelyn F. McKnight Brain Institute, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA Department of Neurology, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA
Publication Details: Journal of cerebral blood flow and metabolism, Vol.35(1), pp.121-130
Publisher: United States
Grant note: R01 NS054147 / NINDS NIH HHS NS054147 / NINDS NIH HHS R29 NS034773 / NINDS NIH HHS NS45676 / NINDS NIH HHS R01 NS045676 / NINDS NIH HHS NS34773 / NINDS NIH HHS R01 NS034773 / NINDS NIH HHS
Academic Unit: Miller School of Medicine; UMMG Department of Neurology; UMMG Dept of Neurological Surgery
Language: English
Resource Type: Journal article
PMID: 25370861
PMCID: PMC4294405
Record Identifier: 991031575403102976