nAChRs gene expression and neuroinflammation in APPswe/PS1dE9 transgenic mouse

An evaluation of the APPswe/PS1dE9 transgenic AD mouse, presenting with the toxic A beta 1-42 deposition found in human AD, allowed us to characterize time-dependent changes in inflammatory and cholinergic markers present in AD. Astrogliosis was observed in cortex and hippocampus, with cellular loss occurring in the same areas in which A beta plaques were present. In this setting, we found early significantly elevated levels of IL-1 beta and TNF alpha gene expression; with the hippocampus showing the highest IL-1 beta expression. To investigate the cholinergic anti-inflammatory pathway, the expression of nicotinic receptors (nAChRs) and cholinesterase enzymes also was evaluated. The anti-inflammatory nAChR alpha 7, alpha 4, and beta 2 were particularly increased at 6 months of age in the hippocampus, potentially as a strategy to counteract A beta deposition and the ensuing inflammatory state. A time-dependent subunit switch to the alpha 3 beta 4 type occurred. Whether alpha 3, beta 4 subunits have a pro-inflammatory or an inhibitory effect on ACh stimulation remains speculative. A beta 1-42 deposition, neuronal loss and increased astrocytes were detected, and a time-dependent change in components of the cholinergic anti-inflammatory pathway were observed. A greater understanding of time-dependent A beta /nAChRs interactions may aid in defining new therapeutic strategies and novel molecular targets.

Automated summary

Evaluation of the APPswe/PS1dE9 transgenic AD mouse model revealed time-dependent changes in inflammatory and cholinergic markers, with early elevation of IL-1 beta and TNF alpha gene expression. Increased levels of anti-inflammatory nAChR subunits were observed, particularly in the hippocampus, suggesting a response to counteract A beta deposition and inflammation. Time-dependent changes in the cholinergic anti-inflammatory pathway components were detected, offering potential insights for new therapeutic strategies and molecular targets.