Traumatic brain injury upregulates phosphodiesterase expression in the hippocampus

Nicole M. Wilson, David J. Titus, Anthony A. Oliva, Concepcion Furones, Coleen M Atkins

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Traumatic brain injury (TBI) results in significant impairments in hippocampal synaptic plasticity. A molecule critically involved in hippocampal synaptic plasticity, 3’,5’-cyclic adenosine monophosphate, is downregulated in the hippocampus after TBI, but the mechanism that underlies this decrease is unknown. To address this question, we determined whether phosphodiesterase (PDE) expression in the hippocampus is altered by TBI. Young adult male Sprague Dawley rats received sham surgery or moderate parasagittal fluid-percussion brain injury. Animals were analyzed by western blotting for changes in PDE expression levels in the hippocampus. We found that PDE1A levels were significantly increased at 30 min, 1 h and 6 h after TBI. PDE4B2 and 4D2 were also significantly increased at 1, 6, and 24 h after TBI. Additionally, phosphorylation of PDE4A was significantly increased at 6 and 24 h after TBI. No significant changes were observed in levels of PDE1B, 1C, 3A, 8A, or 8B between 30 min to 7 days after TBI. To determine the spatial profile of these increases, we used immunohistochemistry and flow cytometry at 24 h after TBI. PDE1A and phospho-PDE4A localized to neuronal cell bodies. PDE4B2 was expressed in neuronal dendrites, microglia and infiltrating CD11b+ immune cells. PDE4D was predominantly found in microglia and infiltrating CD11b+ immune cells. To determine if inhibition of PDE4 would improve hippocampal synaptic plasticity deficits after TBI, we treated hippocampal slices with rolipram, a pan-PDE4 inhibitor. Rolipram partially rescued the depression in basal synaptic transmission and converted a decaying form of long-term potentiation (LTP) into long-lasting LTP. Overall, these results identify several possible PDE targets for reducing hippocampal synaptic plasticity deficits and improving cognitive function acutely after TBI.

Original languageEnglish (US)
Article number5
JournalFrontiers in Systems Neuroscience
Volume10
Issue numberFEB
DOIs
StatePublished - Feb 5 2016

Fingerprint

Phosphoric Diester Hydrolases
Hippocampus
Up-Regulation
Neuronal Plasticity
Rolipram
Long-Term Potentiation
Microglia
Traumatic Brain Injury
Phosphodiesterase 4 Inhibitors
Percussion
Dendrites
Synaptic Transmission
Cyclic AMP
Brain Injuries
Cognition
Sprague Dawley Rats
Young Adult
Flow Cytometry
Down-Regulation
Western Blotting

Keywords

  • cAMP
  • CREB
  • Fluid-percussion
  • Hippocampus
  • Inflammation
  • Phosphodiesterase
  • Traumatic brain injury

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Cellular and Molecular Neuroscience
  • Cognitive Neuroscience
  • Developmental Neuroscience

Cite this

Traumatic brain injury upregulates phosphodiesterase expression in the hippocampus. / Wilson, Nicole M.; Titus, David J.; Oliva, Anthony A.; Furones, Concepcion; Atkins, Coleen M.

In: Frontiers in Systems Neuroscience, Vol. 10, No. FEB, 5, 05.02.2016.

Research output: Contribution to journalArticle

Wilson, Nicole M. ; Titus, David J. ; Oliva, Anthony A. ; Furones, Concepcion ; Atkins, Coleen M. / Traumatic brain injury upregulates phosphodiesterase expression in the hippocampus. In: Frontiers in Systems Neuroscience. 2016 ; Vol. 10, No. FEB.
@article{94f0a0f4ee954d55af69021354bb6ce7,
title = "Traumatic brain injury upregulates phosphodiesterase expression in the hippocampus",
abstract = "Traumatic brain injury (TBI) results in significant impairments in hippocampal synaptic plasticity. A molecule critically involved in hippocampal synaptic plasticity, 3’,5’-cyclic adenosine monophosphate, is downregulated in the hippocampus after TBI, but the mechanism that underlies this decrease is unknown. To address this question, we determined whether phosphodiesterase (PDE) expression in the hippocampus is altered by TBI. Young adult male Sprague Dawley rats received sham surgery or moderate parasagittal fluid-percussion brain injury. Animals were analyzed by western blotting for changes in PDE expression levels in the hippocampus. We found that PDE1A levels were significantly increased at 30 min, 1 h and 6 h after TBI. PDE4B2 and 4D2 were also significantly increased at 1, 6, and 24 h after TBI. Additionally, phosphorylation of PDE4A was significantly increased at 6 and 24 h after TBI. No significant changes were observed in levels of PDE1B, 1C, 3A, 8A, or 8B between 30 min to 7 days after TBI. To determine the spatial profile of these increases, we used immunohistochemistry and flow cytometry at 24 h after TBI. PDE1A and phospho-PDE4A localized to neuronal cell bodies. PDE4B2 was expressed in neuronal dendrites, microglia and infiltrating CD11b+ immune cells. PDE4D was predominantly found in microglia and infiltrating CD11b+ immune cells. To determine if inhibition of PDE4 would improve hippocampal synaptic plasticity deficits after TBI, we treated hippocampal slices with rolipram, a pan-PDE4 inhibitor. Rolipram partially rescued the depression in basal synaptic transmission and converted a decaying form of long-term potentiation (LTP) into long-lasting LTP. Overall, these results identify several possible PDE targets for reducing hippocampal synaptic plasticity deficits and improving cognitive function acutely after TBI.",
keywords = "cAMP, CREB, Fluid-percussion, Hippocampus, Inflammation, Phosphodiesterase, Traumatic brain injury",
author = "Wilson, {Nicole M.} and Titus, {David J.} and Oliva, {Anthony A.} and Concepcion Furones and Atkins, {Coleen M}",
year = "2016",
month = "2",
day = "5",
doi = "10.3389/fnsys.2016.00005",
language = "English (US)",
volume = "10",
journal = "Frontiers in Systems Neuroscience",
issn = "1662-5137",
publisher = "Frontiers Research Foundation",
number = "FEB",

}

TY - JOUR

T1 - Traumatic brain injury upregulates phosphodiesterase expression in the hippocampus

AU - Wilson, Nicole M.

AU - Titus, David J.

AU - Oliva, Anthony A.

AU - Furones, Concepcion

AU - Atkins, Coleen M

PY - 2016/2/5

Y1 - 2016/2/5

N2 - Traumatic brain injury (TBI) results in significant impairments in hippocampal synaptic plasticity. A molecule critically involved in hippocampal synaptic plasticity, 3’,5’-cyclic adenosine monophosphate, is downregulated in the hippocampus after TBI, but the mechanism that underlies this decrease is unknown. To address this question, we determined whether phosphodiesterase (PDE) expression in the hippocampus is altered by TBI. Young adult male Sprague Dawley rats received sham surgery or moderate parasagittal fluid-percussion brain injury. Animals were analyzed by western blotting for changes in PDE expression levels in the hippocampus. We found that PDE1A levels were significantly increased at 30 min, 1 h and 6 h after TBI. PDE4B2 and 4D2 were also significantly increased at 1, 6, and 24 h after TBI. Additionally, phosphorylation of PDE4A was significantly increased at 6 and 24 h after TBI. No significant changes were observed in levels of PDE1B, 1C, 3A, 8A, or 8B between 30 min to 7 days after TBI. To determine the spatial profile of these increases, we used immunohistochemistry and flow cytometry at 24 h after TBI. PDE1A and phospho-PDE4A localized to neuronal cell bodies. PDE4B2 was expressed in neuronal dendrites, microglia and infiltrating CD11b+ immune cells. PDE4D was predominantly found in microglia and infiltrating CD11b+ immune cells. To determine if inhibition of PDE4 would improve hippocampal synaptic plasticity deficits after TBI, we treated hippocampal slices with rolipram, a pan-PDE4 inhibitor. Rolipram partially rescued the depression in basal synaptic transmission and converted a decaying form of long-term potentiation (LTP) into long-lasting LTP. Overall, these results identify several possible PDE targets for reducing hippocampal synaptic plasticity deficits and improving cognitive function acutely after TBI.

AB - Traumatic brain injury (TBI) results in significant impairments in hippocampal synaptic plasticity. A molecule critically involved in hippocampal synaptic plasticity, 3’,5’-cyclic adenosine monophosphate, is downregulated in the hippocampus after TBI, but the mechanism that underlies this decrease is unknown. To address this question, we determined whether phosphodiesterase (PDE) expression in the hippocampus is altered by TBI. Young adult male Sprague Dawley rats received sham surgery or moderate parasagittal fluid-percussion brain injury. Animals were analyzed by western blotting for changes in PDE expression levels in the hippocampus. We found that PDE1A levels were significantly increased at 30 min, 1 h and 6 h after TBI. PDE4B2 and 4D2 were also significantly increased at 1, 6, and 24 h after TBI. Additionally, phosphorylation of PDE4A was significantly increased at 6 and 24 h after TBI. No significant changes were observed in levels of PDE1B, 1C, 3A, 8A, or 8B between 30 min to 7 days after TBI. To determine the spatial profile of these increases, we used immunohistochemistry and flow cytometry at 24 h after TBI. PDE1A and phospho-PDE4A localized to neuronal cell bodies. PDE4B2 was expressed in neuronal dendrites, microglia and infiltrating CD11b+ immune cells. PDE4D was predominantly found in microglia and infiltrating CD11b+ immune cells. To determine if inhibition of PDE4 would improve hippocampal synaptic plasticity deficits after TBI, we treated hippocampal slices with rolipram, a pan-PDE4 inhibitor. Rolipram partially rescued the depression in basal synaptic transmission and converted a decaying form of long-term potentiation (LTP) into long-lasting LTP. Overall, these results identify several possible PDE targets for reducing hippocampal synaptic plasticity deficits and improving cognitive function acutely after TBI.

KW - cAMP

KW - CREB

KW - Fluid-percussion

KW - Hippocampus

KW - Inflammation

KW - Phosphodiesterase

KW - Traumatic brain injury

UR - http://www.scopus.com/inward/record.url?scp=84962019481&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962019481&partnerID=8YFLogxK

U2 - 10.3389/fnsys.2016.00005

DO - 10.3389/fnsys.2016.00005

M3 - Article

AN - SCOPUS:84962019481

VL - 10

JO - Frontiers in Systems Neuroscience

JF - Frontiers in Systems Neuroscience

SN - 1662-5137

IS - FEB

M1 - 5

ER -