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[P2–081]: POSSIBLE INVOLVEMENT OF CALCIUM CHANNELS IN NEUROPROTECTIVE MECHANISM OF FENOFIBRATE AGAINST 3‐NITROPROPIONIC ACID‐INDUCED HUNTINGTON's DISEASE IN RATS
Author(s) -
Kumar Puneet
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.06.730
Subject(s) - neuroprotection , excitotoxicity , medicine , endocrinology , oxidative stress , neuroinflammation , pharmacology , huntington's disease , neurochemical , glutamate receptor , diltiazem , chemistry , calcium , inflammation , disease , receptor
Alzheimer’s disease (AD) in particular. As well, distinct biometal imaging and role of metal uptake transporters are central to understanding AD pathogenesis and ageing but remain elusive, due inappropriate detection methods. Herein, we report the distribution profile of biometals in the aged brain of the endemic Chilean rodent Octodon degus (O. degus) – a natural model to investigate the role of metals on the onset and progression of AD. Methods:We used laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS), to quantitate the levels of biometals (Fe, Ca, Zn, Cu, and Al) in the brain of aged O.degus. We also assessed the protein expression levels of Cathepsin D, an important marker for lysosomal function, Ab42), the metal transporter ATP13a2, zinc transporters, ZnT(1,3,4,6, 7 and 10), and ZIP7,8 and ZIP14, the major iron/copper regulator IRP2, DMT1, a major transporter of divalent metal species, 5’-aminolevulinate synthase 2 (ALAS2), and the proto-oncogene, FOS. Results: The metals Fe, Ca, Zn, and Cu were specifically enriched in the cortex and hippocampus, which are the regions where amyloid plaques, tau phosphorylation and glial alterations are most commonly reported, whilst Al was enriched in the hippocampus alone. Using whole brain extracts, age-related deregulation of metal trafficking pathways was also observed in O.degus. More specifically, we observed impaired lysosomal function, demonstrated by reduced Cathepsin D protein expression. An age-related reduction in the expression of subunit B2 of V-ATPase, and significant increases in amyloid beta 42 (Ab42), and the metal transporter ATP13a2 were also observed. Although the protein expression levels of the zinc transporters, ZnT(1,3,4,6, and 7), and ZIP7,8 and ZIP14 increased in the brain of aged O.degus, ZnT10, decreased. Although no significant age-related change was observed for the major iron/copper regulator IRP2, we did find a significant increase in the expression of DMT1, a major transporter of divalent metal species, 5’-aminolevulinate synthase 2 (ALAS2), and the proto-oncogene, FOS. Conclusions: Collectively, our data indicate that transition metals may be enriched with age in the brains of O. degus, and metal dyshomeostasis in specific brain regions is age-related.