Early Postnatal Lead Exposure Induces Tau Phosphorylation in the Brain of Young Rats

Abstract

Cognitive impairment is a common feature of both lead exposure and hyperphosphorylation of tau. We, therefore, investigated whether lead exposure would induce tau hyperphosphorylation. Wistar rat pups were exposed to 0.2% lead acetate via their dams’ drinking water from postnatal day 1 to 21. Lead in blood and brain were measured by atomic absorption spectrophotometry and the expression of tau, phos-phorylated tau and various serine/threonine protein phosphatases (PP1, PP2A, PP2B and PP5) in the brain was analyzed by Western blot. Lead exposure significantly impaired learning and resulted in a significant reduction in the expression of tau but increased the phosphorylation of tau at Serl99/202, Thr212/Ser214 and Thr231. PP2A expression decreased, whereas, PP1 and PP5 expression increased in lead-exposed rats. These results demonstrate that early postnatal exposure to lead decrease PP2A expression and induce tau hyperphosphorylation at several serine and threonine residues. Hyperphosphorylation of tau may be a mechanism of Pb-induced deficits in learning and memory.

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Acknowledgements

This work was supported by Kuwait University grants WF01/07. The authors acknowledge the excellent technical assistance provided by Drs. S. Jacob, Lukman Talib and T. S. Srikumar. We acknowledge the support from the Core facility of Health Science Center for allowing us to utilize the facility (Grants GM01/01 and GM01/05). None of the authors declare any conflict of interest.

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Correspondence to A. Rahman.

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Rahman, A., Khan, K.M., Al-Khaledi, G. et al. Early Postnatal Lead Exposure Induces Tau Phosphorylation in the Brain of Young Rats. BIOLOGIA FUTURA 63, 411–425 (2012). https://doi.org/10.1556/ABiol.63.2012.4.1

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Keywords

  • Tau
  • hyperphosphorylation
  • lead-protein phosphatases
  • PP2A