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Neurochemical Research, Vol. 30, Nos. 6/7, June/July 2005 ( 2005), pp. 927935
DOI: 10.1007/s11064-005-6967-4Oxidative Stress and Inammation in Brain Aging: Nutritional
ConsiderationsJ.A. Joseph,1,3 B. Shukitt-Hale,1 G. Casadesus,2 and D. Fisher1(Accepted June 15, 2005)Aging can be dened as the condition where stressors are not counteracted by protective
functions, leading to a dysregulation in development. These changes can be translated into
decrements in neuronal functioning accompanied by behavioral declines, such as decreases in
motor and cognitive performance, in both humans and animals. When coupled with genetic
alterations, the ultimate expression of these changes is seen in diseases such as Alzheimer
disease (AD). This association will be discussed in the last section of this chapter. In this
review we will describe motor and cognitive decits in behavior due to aging, and show how
these decits are related to increased vulnerability to oxidative stress, inammation or
signaling. Importantly, using muscarinic receptors as examples, we will also try to show that
the sensitivity to these insults may be dierentially expressed among neurotransmitter receptor
subtypes.KEY WORDS: Aging; behavior; inammation; nutrition; oxidative stress.BEHAVIORAL CHANGES IN AGINGMany behavioral changes that include both
motor (1,2) and cognitive (3) declines during normal aging have been shown in numerous experiments. These studies have revealed that the decits in
motor function include decreases in balance, muscle
strength, and coordination (1). Motor decits are
thought to be the result of either alterations in the
striatal dopamine (DA) system, as the striatum shows
marked neurodegenerative changes with age (4), or in
the cerebellum which also shows age-related alterations (5,6).Accompanying the alterations in motor behavior
are decits in cognitive performance. Observations of
these changes have been made for a number of years on
tasks involving spatial learning and memory (3,710).
Memory alterations appear to occur primarily in secondary memory systems that involve the storing of
new information (4,11). Research has suggested that
various brain regions are involved in aspects of this
storage including: a) the hippocampus which mediates
place learning, b) the prefrontal cortex which is critical
to acquiring procedural knowledge, and c) the dorsomedial striatum which mediates egocentric response
and cue learning (1215). While the mechanisms
involved in both motor and cognitive decits during
aging remain to be discerned, it is clear that oxidative
stress (16) and inammation (17,18)...