Journal article
Aging and a Peripheral Immune Challenge Interact to Reduce Mature Brain-Derived Neurotrophic Factor and Activation of TrkB, PLCγ1, and ERK in Hippocampal Synaptoneurosomes
The Journal of neuroscience, Vol.31(11), pp.4274-4279
03/16/2011
DOI: 10.1523/JNEUROSCI.5818-10.2011
PMCID: 3086395
PMID: 21411668
Abstract
For reasons that are not well understood, aging significantly increases brain vulnerability to challenging life events. High-functioning older individuals often experience significant cognitive decline after an inflammatory event such as surgery, infection, or injury. We have modeled this phenomenon in rodents and have previously reported that a peripheral immune challenge (intraperitoneal injection of live
Escherichia coli
) selectively disrupts consolidation of hippocampus-dependent memory in aged (24-month-old), but not young (3-month-old), F344xBN rats. More recently, we have demonstrated that this infection-evoked memory deficit is mirrored by a selective deficit in long-lasting synaptic plasticity in the hippocampus. Interestingly, these deficits occur in forms of long-term memory and synaptic plasticity known to be strongly dependent on brain-derived neurotrophic factor (BDNF). Here, we begin to test the hypothesis that the combination of aging and an infection might disrupt production or processing of BDNF protein in the hippocampus, decreasing the availability of BDNF for plasticity-related processes at synaptic sites. We find that mature BDNF is markedly reduced in Western blots of hippocampal synaptoneurosomes prepared from aged animals following infection. This reduction is blocked by intra-cisterna magna administration of the anti-inflammatory cytokine IL-1Ra (interleukin 1-specific receptor antagonist). Levels of the pan-neurotrophin receptor p75
NTR
and the BDNF receptor TrkB (tropomyosin receptor kinase B) are not significantly altered in these synaptoneurosomes, but phosphorylation of TrkB and downstream activation of PLCγ1 (phospholipase Cγ1) and ERK (extracellular response kinase) are attenuated—observations consistent with reduced availability of mature BDNF to activate TrkB signaling. These data suggest that inflammation-evoked reductions in BDNF at synapses might contribute to inflammation-evoked disruptions in long-term memory and synaptic plasticity in aging.
Details
- Title: Subtitle
- Aging and a Peripheral Immune Challenge Interact to Reduce Mature Brain-Derived Neurotrophic Factor and Activation of TrkB, PLCγ1, and ERK in Hippocampal Synaptoneurosomes
- Creators
- Giuseppe P. Cortese - University of Colorado BoulderRuth M. Barrientos - University of Colorado BoulderSteven F. Maier - University of Colorado BoulderSusan L. Patterson - University of Colorado Boulder
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.31(11), pp.4274-4279
- Publisher
- Society for Neuroscience
- DOI
- 10.1523/JNEUROSCI.5818-10.2011
- PMID
- 21411668
- PMCID
- 3086395
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Language
- English
- Date published
- 03/16/2011
- Academic Unit
- Iowa Neuroscience Institute
- Record Identifier
- 9984455946502771
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