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The TNFα-Transgenic Rat: Hippocampal Synaptic Integrity, Cognition, Function, and Post-Ischemic Cell Loss
L Creed Pettigrew1,2,3,4, Richard J Kryscio2,5, Christopher M Norris2,6
1Paul G. Blazer, Jr. Stroke Research Laboratory, University of Kentucky, Lexington, Kentucky, United States of America.
Plos One
|May 5, 2016
Summary
Chronic elevation of tumor necrosis factor-alpha (TNFα) in transgenic rats increased synaptic plasticity and exacerbated motor deficits after stroke. However, it also protected cortical neurons from ischemic injury.
Area of Science:
- Neuroscience
- Neuroinflammation
- Synaptic Plasticity
Background:
- Tumor necrosis factor-alpha (TNFα) is a key cytokine regulating neuroinflammation, implicated in neurodegenerative diseases.
- Understanding TNFα's role in synaptic function and neuronal response to injury is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the impact of chronically elevated TNFα on hippocampal synaptic function.
- To assess neuronal viability and cognitive recovery in TNFα-overexpressing rats following ischemic stroke (MCAO).
Main Methods:
- Utilized transgenic rats overexpressing a murine TNFα gene.
- Recorded basal synaptic strength and long-term potentiation (LTP) in hippocampal slices.
- Evaluated cognitive and motor functions using the Morris Water Maze and Rotarod tasks post-MCAO.
Main Results:
- Elevated TNFα led to significantly greater LTP, indicating potential synaptic hyperexcitability.
- TNFα transgenic rats exhibited cognitive and motor deficits, with exacerbated motor deficits after MCAO.
- Overexpression of TNFα ameliorated cortical neuron loss following MCAO, despite increased motor impairment.
Conclusions:
- Chronic TNFα elevation enhances synaptic plasticity and offers neuroprotection against ischemic injury.
- Despite neuroprotection, elevated TNFα contributes to cognitive and motor impairments, particularly after stroke.
- Further research is needed to elucidate the dual role of TNFα in neuroinflammation and neuronal function.
