Mortality, oxidative stress and tau accumulation during ageing in parkin null mice.

Abstract:

:Young parkin null (pk-/-) mice have subtle abnormalities of behaviour, dopamine (DA) neurotransmission and free radical production, but no massive loss of DA neurons. We investigated whether these findings are maintained while ageing. Pk-/- mice have reduced life span and age-related reduced exploratory behaviour, abnormal walking and posture, and behaviours similar to those of early Parkinson's disease (PD), reduced number of nigrostriatal DA neurons and proapoptotic shifts in the survival/death proteins in midbrain and striatum. Contrary to young pk-/- animals 24-month-old pk-/- mice do not have compensatory elevation of GSH in striatum, glutathione reductase (GR) and glutathione peroxidase (GPx) activities are increased and catalase unchanged. Aged pk-/- mice accumulate high levels of tau and fail to up-regulate CHIP and HSP70. Our results suggest that aged pk-/- mice lack of the compensatory mechanisms that maintain a relatively normal DA function in early adulthood. This study could help to explain the effects of ageing in patients with genetic risks for Parkinson's disease.

journal_name

J Neurochem

authors

Rodríguez-Navarro JA,Casarejos MJ,Menéndez J,Solano RM,Rodal I,Gómez A,Yébenes JG,Mena MA

doi

10.1111/j.1471-4159.2007.04762.x

subject

Has Abstract

pub_date

2007-10-01 00:00:00

pages

98-114

issue

1

eissn

0022-3042

issn

1471-4159

pii

JNC4762

journal_volume

103

pub_type

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