Perinatal exposure to lead (Pb) affects the function of Tau and Tau-kinases in the rat brain

• Autorzy: Gassowska M. , Baranowska-Bosiacka I. , Moczydlowska J. , Czapski G.A. , Falkowska A. , Struzynska L. , Adamczyk A.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: Hyperphosphorylation of Tau is involved in the pathomechanism of neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. Epidemiological data suggest the significance of early life exposure to lead (Pb) in etiology of disorders affecting brain function. However, the precise mechanisms by which Pb exerts neurotoxic effects are not fully elucidated. In this study, we investigated the effect of perinatal exposure to Pb on Tau pathology in selected rat brain structures: forebrain cortex (FC), cerebellum (C) and hippocampus (H). Concomitantly, we examined the ultrastructural alterations in these regions. Furthermore, the involvement of two major Tau-kinases: glycogen synthase kinase-3 beta (GSK-3β) and cyclin-dependent kinase 5 (CDK5) in Pb-induced Tau modification was analysed. RESULTS: Our data revealed that pre- and neonatal exposure of rats to Pb (concentration in rat offspring’s blood below a ‘safe level’) evoked significant increase in the phosphorylation of Tau at Ser396 with parallel rise in the level of total Tau protein in FC and C. Moreover, in these brain structures, GSK-3β activity was increased by phosphorylation of a tyrosine residue – Tyr-216. However, GSK3β phosphorylation on serine residue, Ser-9 was unchanged. Parallel with GSK-3β activation we observed increase of total GSK-3β level in FC from rats subjected to Pb. In Pb-treated cerebellum we showed calpain-dependent cleavage of CDK5-activating protein p35 leading to formation of p25 and CDK5 overactivation. Molecular alterations were accompanied by pathological changes in ultrastructure of all examined brain structures from rats subjected to Pb. CONCLUSION: Perinatal exposure to lead induces Tau modification in the rat cortex and cerebellum. We suggest that its neurotoxic effect might be mediated, at least in part, by GSK-3β and CDK5- catalysed Tau hyperphosphorylation, leading to impairment of cytoskeleton stability. Supported from MMRC statutory theme 8.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S60-S61

Twórcy

autor

Gassowska M.

• Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Baranowska-Bosiacka I.

• Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland

autor

Moczydlowska J.

• Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Czapski G.A.

• Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Falkowska A.

• Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland

autor

Struzynska L.

• Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Adamczyk A.

• Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland