Noradrenergic dysfunction accelerates LPS-elicited inflammation-related ascending sequential neurodegeneration and deficits in non-motor/motor functions.

Noradrenergic dysfunction accelerates LPS-elicited inflammation-related ascending sequential neurodegeneration and deficits in non-motor/motor functions. Brain Behav Immun. 2019 Jun 24;: Authors: Song S, Wang Q, Jiang L, Oyarzabal E, Riddick NV, Wilson B, Moy SS, Shih YI, Hong JS Abstract The loss of central norepinephrine (NE) released by neurons of the locus coeruleus (LC) occurs with aging, and is thought to be an important factor in producing the many of the nonmotor symptoms and exacerbating the degenerative process in animal models of Parkinson's disease (PD). We hypothesize that selectively depleting noradrenergic LC neurons prior to the induction of chronic neuroinflammation may not only accelerate the rate of progressive neurodegeneration throughout the brain, but may exacerbate nonmotor and motor behavioral phenotypes that recapitulate symptoms of PD. For this reason, we used a "two-hit" mouse model whereby brain NE were initially depleted by DSP-4 one week prior to exposing mice to LPS. We found that pretreatment with DSP-4 potentiated LPS-induced sequential neurodegeneration in SNpc, hippocampus, and motor cortex, but not in VTA and caudate/putamen. Mechanistic study revealed that DSP-4 enhanced LPS-induced microglial activation and subsequently elevated neuronal oxidative stress in affected brain regions in a time-dependent pattern. To further characterize the effects of DSP-4 on non-motor and motor symptoms in the LPS m...
Source: Brain, Behavior, and Immunity - Category: Neurology Authors: Tags: Brain Behav Immun Source Type: research