TNF-α–mediated reduction in inhibitory neurotransmission precedes sporadic Alzheimer’s disease pathology in young Trem2 rats
Siqiang Ren, Lionel Breuillaud, Wen Yao, Tao Yin, Kelly A. Norris, Simone P. Zehntner, Luciano D'adamio
Abstract
rats. This decrease is due to acute and reversible action of TNF-α and is not associated with increased human-Aβ levels and AD pathology. Thus, the p.R47H variant changes the excitatory/inhibitory balance, favoring excitation. This imbalance could potentiate glutamate excitotoxicity and contribute to neuronal dysfunction, enhanced neuronal death, and neurodegeneration. Future studies will determine whether this imbalance represents an early, Aβ-independent pathway leading to dementia and may reveal the AD-modifying therapeutic potential of TNF-α inhibition in the central nervous system.
Topics & Concepts
TREM2Inhibitory postsynaptic potentialNeurotransmissionDiseaseMedicineTumor necrosis factor alphaInflammationMicrogliaPathologyReceptorNeuroscienceBiologyInternal medicineAlzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsTryptophan and brain disorders