Abstract
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.
Highlights
Mast cells derived from hematopoietic progenitors are multifunctional antigen presenting cells present in the tissues throughout the body (Kalesnikoff and Galli, 2008; KrystelWhittemore et al, 2015; Galli and Gaudenzio, 2017)
A recent study reported that mast cells are the first responders in intracerebral hemorrhage (ICH) and promote blood brain barrier (BBB) breach, edema formation, recruit inflammatory cells, and amplify brain injury (Yehya and Torbey, 2017). These findings clearly indicate that mast cells play an important role in the neuroinflammatory responses after the brain injuries or traumatic brain injury (TBI) and that the enhanced neuroinflammation can predispose to the pathogenesis of Alzheimer’s disease (AD)
During the stress conditions, elevated inflammatory mediators cross BBB and induce/augment neuroinflammation that accelerates the pathogenesis of AD. These findings indicate that stress accompanied with chronic inflammation in Post-traumatic stress disorder (PTSD) could lead to neurodegeneration in diseases such as AD
Summary
Mast cells derived from hematopoietic progenitors are multifunctional antigen presenting cells present in the tissues throughout the body (Kalesnikoff and Galli, 2008; KrystelWhittemore et al, 2015; Galli and Gaudenzio, 2017). Mast cells play a major role in neuroinflammatory conditions including neurodegenerative diseases, stroke, MS, TBI by increasing the BBB permeability and activating the brain resident immune cells microglia, and T-cells (Nakae et al, 2006; Ribatti, 2015). As mast cells are implicated in brain injury, stress, and PTSD, activation of mast cells in these conditions could increase neuroinflammation and thereby accelerate the onset and progression of AD.
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