title: The TNFα-Transgenic Rat: Hippocampal Synaptic Integrity, Cognition, Function, and Post-Ischemic Cell Loss.
abstract: 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 artery occlusion (MCAO). Basal CA3-CA1 synaptic strength, recorded in acute brain slices, was not significantly different between eight-week-old TNFα Tg rats and non-Tg rats. In contrast, slices from TNFα 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 TNFα. Cognitive and motor deficits (assessed on the Morris Water Maze and Rotarod task, respectively) were present in TNFα 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.
authors.affiliation: Paul G. Blazer, Jr. Stroke Research Laboratory, University of Kentucky, Lexington, Kentucky, United States of America.|Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, United States of America.|Department of Neurology, University of Kentucky, Lexington, Kentucky, United States of America.|Veterans Administration (VA) Medical Center, Lexington, Kentucky, United States of America.
authors.forename: L Creed
authors.initials: LC
authors.lastname: Pettigrew
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, United States of America.|Department of Statistics and School of Public Health, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Kryscio
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, United States of America.|Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Norris
mesh_terms: D000818:Animals; D003071:Cognition / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D051381:Rats; D055647:Rats, Transgenic; D009435:Synaptic Transmission / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha