The Synergy of Aging and LPS Exposure in a Mouse Model of Parkinson’s Disease

Abstract

Aging is an inevitable physiological challenge occurring in organisms over time, and is also the most important risk factor of neurodegenerative diseases. In this study, we observed cellular and molecular changes of different age mice and LPS-induced Parkinson disease (PD) model. The results showed that behavioral performance and dopaminergic (DA) neurons were declined, accompanied by increased expression of pro-inflammatory factors (TLR2, p-NF-kB-p65, IL-1β and TNF-α), as well as pro-oxidative stress factor gp91phox in aged mice compared with young mice. Aging exaggerated inflammatory M1 microglia, and destroyed the balance between oxidation and anti-oxidation. The intranasal LPS instillation induced PD model in both young and aged mice. The poor behavioral performance and the loss of DA neurons as well as TLR2, p-NF-kB-p65, IL-1β, TNF-α, iNOS and gp91phox were further aggravated in LPS-aged mice. Interestingly, the expression of Nrf2 and HO-1 was up-regulated by LPS only in young LPS-PD mice, but not in aged mice. The results indicate that the synergy of aging process and LPS exposure may prominently aggravate the DA neurons loss caused by more serious neuroinflammation and oxidative stress in the brain.

The TrkB agonist 7,8-dihydroxyflavone improves sensory-motor performance and reduces lipid peroxidation in old mice

“…High amount of neuroinflammation could have hazardous effects on synaptic proteins and other proteins. The increased neuroinflammation in old animals has also been shown in other studies (Buchanan et al 2008;Rancán et al 2017;Zhao et al 2018). In general, in the brain, neuronal inflammation and oxidative stress are related to each other (Durany et al 1999;Floyd and Hensley 2002).…”

Contra-Directional Expression of Plasma Superoxide Dismutase with Lipoprotein Cholesterol and High-Sensitivity C-reactive Protein as Important Markers of Parkinson’s Disease Severity

“…Evidence is now overwhelming that inflammatory responses manifested by glial reactions, increased expression of inflammatory cytokines, and other toxic mediators are important contributors to the progressive loss of nigral dopaminergic (DA) neurons in PD patients. Previous studies found that the aging process can exaggerate the inflammatory responses and aggravate the DA neurons loss in the brain (Zhao et al, 2018). Additionally, the existence of ongoing inflammatory processes affects the modulation of neurogenesis, for example, TNFα affects the differentiation and proliferation of neural stem cells by up-regulation of Ascl2 (Liu et al, 2019).…”

“…Parkinson's disease (PD) is the second common age-related neurodegenerative disease following Alzheimer's disease (AD) due to the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and striatum (Zhao et al, 2018;Li et al, 2019;Qian and Huang, 2019). It is clinically characterized by resting tremor, rigidity, bradykinesia, and postural instability (Chomiak et al, 2018;Gao et al, 2018;Ray Chaudhuri et al, 2018;Sun et al, 2018).…”

P2X4R Overexpression Upregulates Interleukin-6 and Exacerbates 6-OHDA-Induced Dopaminergic Degeneration in a Rat Model of PD

“…Neuroimaging-driven brain age estimation has shown a significantly “older-appearing” brain of PD, and the aging of white matter is more serious than that of gray matter (Beheshti et al, 2020 ). Aging exaggerates inflammatory M1 microglia, impairs the DA neurons, and increases the expression of pro-inflammatory and pro-oxidative stress factors (Zhao et al, 2018 ). PET imaging studies in vivo showed the proliferation of microglia was in parallel with the appearance of pathological α-syn and neuronal death in PD patients (Zheng et al, 2020 ).…”

“…Although the precise etiology of PD is still under exploration, genetic and environment factors (including pesticides, metals and solvents exposures, rural living, etc. ), aging, autophagy, oxidative stress, renin-angiotensin system, together with changes in gut microbial composition and neuroimmunity are suggested to contribute to the neurodegeneration of DA neurons (Rangel-Barajas et al, 2015 ; Lai et al, 2018 ; Zhao et al, 2018 ; Adav and Sze, 2020 ; Zheng et al, 2020 ). Recently, the influence of dysregulated higher inflammatory response in the pathogenesis of central nervous system (CNS) diseases is attracting considerable attention (Hunot and Hirsch, 2003 ; Shen et al, 2019 ; Zhu et al, 2019 ; Yang et al, 2020 ).…”