Hypothalamic mast cells

From: <a id="null" class="null" href="http://jpet.aspetjournals.org/content/jpet/early/2018/08/03/jpet.118.250845.full.pdf">http://jpet.aspetjournals.org/content/jpet/early/2018/08/03/jpet.118.250845.full.pdf</a>

Hypothalamic mast cells are stimulated by stress-associated triggers such as CRH, HK-1 and SP along with mtDNA and IL-33, some derived from nasal cavity, while others may reach the area through a disrupted blood-brain barrier or through lymphatics. Stimulated mast cells then secrete molecules such as CXCL8, NT, TNF, tryptase and mtDNA, (CXCL) which activate microglia to secrete more inflammatory molecules especially, IL-1β, IL-6, and CXCL8 that further disrupt homeostasis, causes mitochondrial dysfunction and contribute to symptoms of ME/CFS. Luteolin could inhibit these processes at different steps

The ME/CFS phenotype has been associated with abnormalities in energy metabolism, apparently due to mitochondrial dysfunction, in the absence of mitochondrial diseases, resulting in reduced oxidative metabolism, mitochondria may be further contributing to the ME/CSF symptomatology by extracellular secretion of mitochondrial DNA, which could act as an “innate” pathogen and create an auto-inflammatory state in the hypothalamus. We propose that stimulation of hypothalamic mast cells by environmental neuroimmune pathogenic and stress triggers activates microglia leading to focal inflammation in the brain and disturbed homeostasis. This process could be targeted for the development of novel effective treatments.

stimulation of hypothalamic mast cells by environmental neuroimmune pathogenic and stress triggers activates microglia leading to focal inflammation in the brain