Student Center for Research and Advanced Studies of the National Polytechnic Institute Mexico, Mexico City, Mexico
Disclosure(s):
Jesus Lopez-Castillo: No financial relationships to disclose
Introduction/Rationale: Aging is importantly associated to the development of neurodegenerative diseases, including those affecting the motor control and striatum function. It is clear the need to study those changes affecting that brain nucleus during aging, such as the neuroinflammatory phenomenon. This project was directed to evaluate the possible age-related changes in the inflammatory response against an excitotoxic stimulus through the evaluation of the RAGE/S100B axis, exploring at the same time the role of mast cells (MC), one of the less studied cell elements in the brain.
Methods: We used mice of different ages (16, 64 and 80 weeks), in which we induced an excitotoxic response by the unilateral administration of the NMDA agonist quinolic acid (QA), directly into the striatum of WT (C57BL6/J) and mast cell-deficient c-Kit Wsh/Wsh (Wsh) mice. After QA administration we measured the neurological damage through the evaluation of ipsilateral turns induced by apomorphine. Then, the integrity of perineuronal nets (PNNs), as well as the presence of different inflammatory markers like S100B protein, RAGE receptor and different cytokines was assessed.
Results: Results obtained to date demonstrate a differential expression of inflammatory components between C57 and Wsh mice after QA administration, with an increase in RAGE receptor in young male mice striatum. This parameter correlates with a major PNNs degeneration and higher levels in the expression of inflammatory cytokines. A reduction in the expression of components of the inflammatory response was observed in aging.
Conclusion: MC seem to be central components in the magnification of the neuroinflammatory response in the excitotoxic QA-induced model. The absence of response in MC-deficient mice results in a decreased inflammation and less neuronal damage. Also, aged mice display a reduced inflammatory capacity that may be related with the brain frailty observed in aging.
