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The TNF?-Transgenic Rat: Hippocampal Synaptic Integrity, Cognition, Function, and Post-Ischemic Cell Loss.


ABSTRACT: The cytokine, tumor necrosis factor ? (TNF?), is a key regulator of neuroinflammation linked to numerous neurodegenerative conditions and diseases. The present study used transgenic rats that overexpress a murine TNF? gene, under the control of its own promoter, to investigate the impact of chronically elevated TNF? on hippocampal synaptic function. Neuronal viability and cognitive recovery in TNF? Tg rats were also determined following an ischemic insult arising from reversible middle cerebral artery occlusion (MCAO). Basal CA3-CA1 synaptic strength, recorded in acute brain slices, was not significantly different between eight-week-old TNF? Tg rats and non-Tg rats. In contrast, slices from TNF? Tg rats showed significantly greater levels of long-term potentiation (LTP) in response to 100 Hz stimulation, suggesting that synaptic networks may be hyperexcitable in the context of elevated TNF?. Cognitive and motor deficits (assessed on the Morris Water Maze and Rotarod task, respectively) were present in TNF? Tg rats in the absence of significant differences in the loss of cortical and hippocampal neurons. TNF overexpression exacerbated MCAO-dependent deficits on the rotarod, but ameliorated cortical neuron loss in response to MCAO.

SUBMITTER: Pettigrew LC 

PROVIDER: S-EPMC4856338 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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The TNFα-Transgenic Rat: Hippocampal Synaptic Integrity, Cognition, Function, and Post-Ischemic Cell Loss.

Pettigrew L Creed LC   Kryscio Richard J RJ   Norris Christopher M CM  

PloS one 20160504 5


The cytokine, tumor necrosis factor α (TNFα), is a key regulator of neuroinflammation linked to numerous neurodegenerative conditions and diseases. The present study used transgenic rats that overexpress a murine TNFα gene, under the control of its own promoter, to investigate the impact of chronically elevated TNFα on hippocampal synaptic function. Neuronal viability and cognitive recovery in TNFα Tg rats were also determined following an ischemic insult arising from reversible middle cerebral  ...[more]

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