Treadmill exercise ameliorates dopaminergic neuronal loss through suppressing microglial activation in Parkinson's disease mice

Sung, Yun Hee; Kim, Shin Chul; Hong, Hoon Pyo; Park, Chang Youl; Shin, Minsoo; Kim, Sang Hoon; Seo, Jin Hee; Kim, Dae Young; Kim, Dong Je; Cho, Han Jin

doi:10.1016/j.lfs.2012.10.003

Cited by 115 publications

(94 citation statements)

References 47 publications

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“…Previous studies in aged mice demonstrated that access to running wheels decreased microglia positive cells in the hippocampus (23,24). In addition, 4 wk of exercise training in a mice model of Parkinson's disease suppressed microglia activation in the substantia nigra pars compacta and striatum (40). Therefore, our data suggest that exercise training is able to inhibit microglia activation, which explains, at least in part, the autonomic adaptations in the trained SHR.…”

Section: Discussionsupporting

confidence: 65%

Aerobic training normalizes autonomic dysfunction, HMGB1 content, microglia activation and inflammation in hypothalamic paraventricular nucleus of SHR

Masson

Nair

Soares

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Masson GS, Nair AR, Silva Soares PP, Michelini LC, Francis J. Aerobic training normalizes autonomic dysfunction, HMGB1 content, microglia activation and inflammation in hypothalamic paraventricular nucleus of SHR. Am J Physiol Heart Circ Physiol 309: H1115-H1122, 2015. First published August 7, 2015; doi:10.1152/ajpheart.00349.2015.-Exercise training (ExT) is recommended to treat hypertension along with pharmaceutical antihypertensive therapies. Effects of ExT in hypothalamic content of high mobility box 1 (HMGB1) and microglial activation remain unknown. We examined whether ExT would decrease autonomic and cardiovascular abnormalities in spontaneously hypertensive rats (SHR), and whether these effects were associated with decreased HMGB1 content, microglial activation, and inflammation in the hypothalamic paraventricular nucleus (PVN). Normotensive Wistar-Kyoto (WKY) rats and SHR underwent moderate-intensity ExT for 2 wk. After ExT, cardiovascular (heart rate and arterial pressure) and autonomic parameters (arterial pressure and heart rate variability, peripheral sympathetic activity, cardiac vagal activity, and baroreflex function) were measured in conscious and freely-moving rats through chronic arterial and venous catheterization. Cerebrospinal fluid, plasma, and brain were collected for molecular and immunohistochemistry analyses of the PVN. In addition to reduced heart rate variability, decreased vagal cardiac activity and increased mean arterial pressure, heart rate, arterial pressure variability, cardiac, and vasomotor sympathetic activity, SHR had higher HMGB1 protein expression, IB-␣ phosphorylation, TNF-␣ and IL-6 protein expression, and microglia activation in the PVN. These changes were accompanied by higher plasma and cerebrospinal fluid levels of HMGB1. The ExT ϩ SHR group had decreased expression of HMGB1, CXCR4, SDF-1, and phosphorylation of p42/44 and IB-␣. ExT reduced microglial activation and proinflammatory cytokines content in the PVN, and improved autonomic control as well. Data suggest that training-induced downregulation of activated HMGB1/CXCR4/microglia/proinflammatory cytokines axis in the PVN of SHR is a prompt neural adaptation to counterbalance the deleterious effects of inflammation on autonomic control. exercise training; baroreflex; brain inflammation; CXCR4; hypertension NEW & NOTEWORTHY Spontaneously hypertensive rats have increased HMGB1 content and CXCR4 signaling in the hypothalamic paraventricular nucleus, which contributes to microglial activation, proinflammatory cytokines production, and, finally, to autonomic dysfunction. Aerobic training decreases HMGB1 content, microglia activation and proinflammatory cytokines expression by inhibiting HMGB1-CXCR4 signaling pathway in the hypothalamic paraventricular nucleus. Aerobic training induces neuroinflammatory adaptations and autonomic benefits independent of the arterial pressure fall.AUTONOMIC DYSFUNCTION is defined as a misbalance between sympathetic and vagal activity associated with baroreflex dysfunction and increased a...

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Section: Discussionsupporting

confidence: 65%

Aerobic training normalizes autonomic dysfunction, HMGB1 content, microglia activation and inflammation in hypothalamic paraventricular nucleus of SHR

Masson

Nair

Soares

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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“…Many studies of similar chronic MPTPp regimens have described deficits in motor coordination as assessed by rotating rod performance (e.g., [2,9,13,44,45]), although some studies have not found significant alterations [46]. Some of those studies "pre-trained" the subjects prior to MPTPp treatment [44,45] and although baseline motor coordination assessments were performed in the current study, there was no required criterion or threshold for progression.…”

Section: Discussionmentioning

confidence: 89%

“…For example, when assessed within 48 h of the last MPTP treatment, male mice exhibit increased latencies in pole descent, decreased latencies to remain on a rotating rod, decreased locomotor activity, increased foot faults during beam crossing or grid tests, poor swimming ability, increased tail suspension immobility, increased akinesia and catalepsy, memory impairments in an avoidance task, and olfactory deficits [3,[6][7][8][9][10][11][12]. Similar treatment has also been described to cause long-lasting impairments (up to 6 months post-treatment) on latencies to remain on a rotating rod [2,13,14], in foot slips or gait alterations [15,16], on performance of the cued, but not spatial, version of a water maze task [16], and on baseline and amphetamine-induced locomotor activity [16].…”

Section: Introductionmentioning

confidence: 99%

Chronic MPTP treatment produces hyperactivity in male mice which is not alleviated by concurrent trehalose treatment

Ferguson

Law

Sarkar

2015

Behavioural Brain Research

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“…CD11b is located on the plasma membrane of microglia, and CD11b expression is increased during the microglial activation [6]. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been used in animal models of Parkinson disease, and MPTP administration causes enhanced CD11b expression in the striatum and substantia nigra [7]. …”

Section: Introductionmentioning

confidence: 99%

“…Apoptosis maintains homeostasis; however, inappropriate or excessive apoptosis has been implicated in several types of neurodegenerative disorders, including ischemia [7,11,12]. Apoptosis after cerebral ischemia is one of the major pathways that lead to the process of cell death [13].…”

Section: Introductionmentioning

confidence: 99%

Inhibitory Effects of Isoquinoline Alkaloid Berberine on Ischemia-Induced Apoptosis via Activation of Phosphoinositide 3-Kinase/Protein Kinase B Signaling Pathway

et al. 2014

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PurposeBerberine is a type of isoquinoline alkaloid that has been used to treat various diseases. A neuroprotective effect of berberine against cerebral ischemia has been reported; however, the effects of berberine on apoptosis in relation to reactive astrogliosis and microglia activation under ischemic conditions have not yet been fully evaluated. In the present study, we investigated the effects of berberine on global ischemia-induced apoptosis, and focused on the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in the hippocampus using gerbils.MethodsGerbils received berberine orally once a day for 14 consecutive days, starting one day after surgery. In this study, a step-down avoidance task was used to assess short-term memory. Furthermore, we employed the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay to evaluate DNA fragmentation, immunohistochemistry to investigate glial fibriallary acidic protein, CD11b, and caspase-3, and western blot to assess PI3K, Akt, Bax, Bcl-2, and cytochrome c.ResultsOur results revealed that berberine treatment alleviated ischemia-induced short-term memory impairment. Treatment with berbeine also attenuated ischemia-induced apoptosis and inhibited reactive astrogliosis and microglia activation. Furthermore, berberine enhanced phospho-PI3K and phospho-Akt expression in the hippocampus of ischemic gerbils.ConclusionsBerberine exerted a neuroprotective effect against ischemic insult by inhibiting neuronal apoptosis via activation of the PI3K/Akt signaling pathway. The antiapoptotic effect of berberine was achieved through inhibition of reactive astrogliosis and microglia activation. Berberine may therefore serve as a therapeutic agent for stroke-induced neurourological problems.

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Treadmill exercise ameliorates dopaminergic neuronal loss through suppressing microglial activation in Parkinson's disease mice

Cited by 115 publications

References 47 publications

Aerobic training normalizes autonomic dysfunction, HMGB1 content, microglia activation and inflammation in hypothalamic paraventricular nucleus of SHR

Aerobic training normalizes autonomic dysfunction, HMGB1 content, microglia activation and inflammation in hypothalamic paraventricular nucleus of SHR

Chronic MPTP treatment produces hyperactivity in male mice which is not alleviated by concurrent trehalose treatment

Inhibitory Effects of Isoquinoline Alkaloid Berberine on Ischemia-Induced Apoptosis via Activation of Phosphoinositide 3-Kinase/Protein Kinase B Signaling Pathway

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