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Dysregulation of brain divalent metals ions as a possible cause for lead‐induced deficits in learning and memory
Author(s) -
Khan Khalid M,
Rahman Abdur,
Attur Sreeja M,
Srikumar T. S.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.535.5
Subject(s) - morris water navigation task , chemistry , threonine , divalent , phosphatase , toxicant , serine , endocrinology , medicine , weaning , metal , enzyme , biochemistry , hippocampus , toxicity , organic chemistry
Lead (Pb) is a known toxicant which affects the central nervous system. We have previously shown that the activity/expression of serine/threonine protein phosphatases is dysregulated by Pb exposure (Rahman et al, 2012). Since the activities of several serine/threonine phosphatases are modulated by divalent metal ions, we investigated the blood and brain levels of Cu, Mn and Zn. Wistar rat pups (n=10/group) were exposed to 0.2% Pb‐acetate via their dams’ drinking water from postnatal day (PND) 1 to 21 and directly via drinking water from weaning until PND 30. The control group (n=10) was given regular water. Pb, Cu, Mn and Zn in blood and brain tissues were measured by atomic absorption spectrophotometer. Morris water maze was used to test learning and memory. Mean values of Pb in blood and brain in Pb‐exposed rats were significantly (p < 0.05) higher than in control animals at PND21 and PND30. At PND21 blood and brain levels of Cu, Mn and Zn significantly decreased in the Pb‐exposed rats. At PND30, brain levels of both Cu and Zn were decreased in the Pb‐exposed rats, whereas, brain Mn was not affected. Pb exposure also resulted in significant impairment of learning. These data suggest that exposure to Pb during early postnatal development of brain causes dysregulation of essential divalent metal ions Cu, Mn and Zn. Since these metal ions are necessary co‐factors for many enzymes in the brain, including protein phosphatases, their substantial reduction in the brain of Pb‐exposed rats may result in altered phosphatase activity (PP2A for example) and subsequent functional impairment. One such related metabolic derangement is tau hyperphosphorylation due to decreased PP2A activity. This PP2A‐associated hyperphosphorylation of tau may be involved in Pb‐induced deficits in learning and memory as well.