Cross-Talk between Glia, Neurons and Mast Cells in Neuroinflammation Associated with Parkinson’s Disease

Kempuraj, Duraisamy; Selvakumar, Govindhasamy Pushpavathi; Zaheer, Smita; Thangavel, Ramasamy; Ahmed, Mohammad Ejaz; Raikwar, Sudhanshu P.; Govindarajan, Raghav; Iyer, Shankar S.; Zaheer, Asgar

doi:10.1007/s11481-017-9766-1

Cited by 61 publications

(39 citation statements)

References 76 publications

(119 reference statements)

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“…In addition, mast cells tended to surround ganglion cells, suggesting that mast cells are mediators of neuritis. These findings are consistent with evidence that mast cells mediate neurodegenerative diseases . Previous analysis of gene expression profiles in tissue samples of achalasia demonstrated that toll‐like receptor 4 and interleukin (IL)‐18 are key players involved in neuronal/muscular and neuronal/immunity processes .…”

Section: Discussionsupporting

confidence: 87%

“…These findings are consistent with evidence that mast cells mediate neurodegenerative diseases. 10 Previous analysis of gene expression profiles in tissue samples of achalasia demonstrated that toll-like receptor 4 and interleukin (IL)-18 are key players involved in neuronal/ muscular and neuronal/immunity processes. 35 Both proteins are significantly associated with mast cells in immunity diseases, further supporting our present findings.…”

Section: Discussionmentioning

confidence: 99%

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Mast cell infiltration associated with loss of interstitial cells of Cajal and neuronal degeneration in achalasia

Liu

Chen

Wang

et al. 2019

Neurogastroenterology Motil

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Background Achalasia is a motility disorder of unknown etiology. Previous studies supported the hypothesis that autoimmune‐mediated inflammatory responses produce inhibitory neuronal degeneration. This study was designed to explore the role of mast cells in achalasia. Methods We collected information from 116 patients with achalasia who underwent peroral endoscopic myotomy between December 2016 and May 2017. Lower esophageal sphincter (LES) muscle biopsy was performed in all patients with achalasia, as well as 20 control subjects. The number of mast cells, interstitial cells of Cajal (ICCs), nNOS‐positive cells, and S‐100‐positive cells in the LES were evaluated by immunohistochemistry. Pathological and clinical data were compared between groups. Key Results Compared with controls, the LES of patients with achalasia had significantly fewer ICCs, nNOS‐positive cells, and S‐100‐positive cells and a higher number of mast cells (all P < 0.001). Furthermore, the increased mast cell infiltration was significantly associated with decreased ICCs, nNOS‐positive cells, and S‐100‐positive cells in patients with achalasia (all P < 0.05). Clinically, the number of strongly positive mast cells was highest in patients with type I achalasia and lowest in those with type III achalasia (P < 0.001). In addition, patients with a history of autoimmune disease or viral infection had greater mast cell infiltration in the LES muscle (P = 0.040). Conclusions & Inferences In patients with achalasia, mast cell infiltration in the LES muscle is increased, in association with loss of ICCs and neuronal degeneration. Mast cells may thereby play a crucial role in the development of achalasia.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Mast cell infiltration associated with loss of interstitial cells of Cajal and neuronal degeneration in achalasia

Liu

Chen

Wang

et al. 2019

Neurogastroenterology Motil

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“…Our recent studies have highlighted the role of MCs in brain neuroinflammatory responses, and our findings indicate that significant elevations of MC number and degranulation are associated with postoperative cognitive dysfunction through microglial activation [10]. In addition, altered MC degranulation has also been found in other CNS disorders, such as stroke [11], Parkinson's disease [12], and multiple sclerosis [13]. Microscopic investigations have also demonstrated infiltrated β-tryptase-containing MCs in human brains with amyloid deposits [14].…”

Section: Introductionmentioning

confidence: 53%

The Mast Cell Is an Early Activator of Lipopolysaccharide-Induced Neuroinflammation and Blood-Brain Barrier Dysfunction in the Hippocampus

Wang

Sha

Zhou

et al. 2020

Mediators of Inflammation

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Neuroinflammation contributes to or even causes central nervous system (CNS) diseases, and its regulation is thus crucial for brain disorders. Mast cells (MCs) and microglia, two resident immune cells in the brain, together with astrocytes, play critical roles in the progression of neuroinflammation-related diseases. MCs have been demonstrated as one of the fastest responders, and they release prestored and newly synthesized mediators including histamine, β-tryptase, and heparin. However, temporal changes in MC activation in this inflammation process remain unclear. This study demonstrated that MC activation began at 2 h and peaked at 4 h after lipopolysaccharide (LPS) administration. The number of activated MCs remained elevated until 24 h after LPS administration. In addition, the levels of histamine and β-tryptase in the hippocampus markedly and rapidly increased within 6 h and remained higher than the baseline level within 24 h after LPS challenge. Furthermore, mast cell-deficient KitW-sh/W-sh mice were used to investigate the effects of MCs on microglial and astrocytic activation and blood-brain barrier (BBB) permeability at 4 h after LPS stimulation. Notably, LPS-induced proinflammatory cytokine secretion, microglial activation, and BBB damage were inhibited in KitW-sh/W-sh mice. However, no detectable astrocytic changes were found in WT and KitW-sh/W-sh mice at 4 h after LPS stimulation. Our findings indicate that MC activation precedes CNS inflammation and suggest that MCs are among the earliest participants in the neuroinflammation-initiating events.

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“…Further, we have shown that mast cells also express GMF and suggest that GMF in mast cells may also play an important role in the pathogenesis of neurodegenerative diseases including AD (Kempuraj et al, 2015 ). Additionally, we have also shown that GMF activates mouse and human mast cells to release mast cell specific proteases and other neuroinflammatory mediators that are implicated in neuroinflammation and neurodegeneration in PD and AD (Kempuraj et al, 2015 , 2017a ). We have previously reported enhanced expression of IL-33 and GMF at the vicinity of APs and NFTs in human AD brain (Xiong et al, 2014 ).…”

Section: Mast Cells Neuroinflammation and Admentioning

confidence: 96%

Mast Cell Activation in Brain Injury, Stress, and Post-traumatic Stress Disorder and Alzheimer's Disease Pathogenesis

et al. 2017

Self Cite

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Mast cells are localized throughout the body and mediate allergic, immune, and inflammatory reactions. They are heterogeneous, tissue-resident, long-lived, and granulated cells. Mast cells increase their numbers in specific site in the body by proliferation, increased recruitment, increased survival, and increased rate of maturation from its progenitors. Mast cells are implicated in brain injuries, neuropsychiatric disorders, stress, neuroinflammation, and neurodegeneration. Brain mast cells are the first responders before microglia in the brain injuries since mast cells can release prestored mediators. Mast cells also can detect amyloid plaque formation during Alzheimer's disease (AD) pathogenesis. Stress conditions activate mast cells to release prestored and newly synthesized inflammatory mediators and induce increased blood-brain barrier permeability, recruitment of immune and inflammatory cells into the brain and neuroinflammation. Stress induces the release of corticotropin-releasing hormone (CRH) from paraventricular nucleus of hypothalamus and mast cells. CRH activates glial cells and mast cells through CRH receptors and releases neuroinflammatory mediators. Stress also increases proinflammatory mediator release in the peripheral systems that can induce and augment neuroinflammation. Post-traumatic stress disorder (PTSD) is a traumatic-chronic stress related mental dysfunction. Currently there is no specific therapy to treat PTSD since its disease mechanisms are not yet clearly understood. Moreover, recent reports indicate that PTSD could induce and augment neuroinflammation and neurodegeneration in the pathogenesis of neurodegenerative diseases. Mast cells play a crucial role in the peripheral inflammation as well as in neuroinflammation due to brain injuries, stress, depression, and PTSD. Therefore, mast cells activation in brain injury, stress, and PTSD may accelerate the pathogenesis of neuroinflammatory and neurodegenerative diseases including AD. This review focusses on how mast cells in brain injuries, stress, and PTSD may promote the pathogenesis of AD. We suggest that inhibition of mast cells activation and brain cells associated inflammatory pathways in the brain injuries, stress, and PTSD can be explored as a new therapeutic target to delay or prevent the pathogenesis and severity of AD.

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Cross-Talk between Glia, Neurons and Mast Cells in Neuroinflammation Associated with Parkinson’s Disease

Cited by 61 publications

References 76 publications

Mast cell infiltration associated with loss of interstitial cells of Cajal and neuronal degeneration in achalasia

Mast cell infiltration associated with loss of interstitial cells of Cajal and neuronal degeneration in achalasia

The Mast Cell Is an Early Activator of Lipopolysaccharide-Induced Neuroinflammation and Blood-Brain Barrier Dysfunction in the Hippocampus

Mast Cell Activation in Brain Injury, Stress, and Post-traumatic Stress Disorder and Alzheimer's Disease Pathogenesis

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