The Tnf Alpha-Transgenic Rat: Hippocampal Synaptic Integrity, Cognition, Function, And Post-Ischemic Cell Loss

The cytokine, tumor necrosis factor alpha (TNF alpha), is a key regulator of neuroinflammation linked to numerous neurodegenerative conditions and diseases. The present study used transgenic rats that overexpress a murine TNF alpha gene, under the control of its own promoter, to investigate the impact of chronically elevated TNF alpha on hippocampal synaptic function. Neuronal viability and cognitive recovery in TNF alpha 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 alpha Tg rats and non-Tg rats. In contrast, slices from TNF alpha 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 alpha. Cognitive and motor deficits (assessed on the Morris Water Maze and Rotarod task, respectively) were present in TNF alpha 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.