Summary An animal’s survival strongly depends on a nervous system that can rapidly process and integrate the changing quality of its environment and promote the most appropriate physiological responses. This is amply demonstrated in the nematode worm Caenorhabditis elegans, where its sensory system has been shown to impact multiple physiological traits that range from behavior and developmental plasticity to longevity. Because of the accessibility of its nervous system and the number of tools available to study and manipulate its neural circuitry, C. elegans has thus become an important model organism in dissecting the mechanisms through which the nervous system promotes survival. Here we review our current understanding of how the C. elegans sensory system affects diverse physiological traits, whose coordination would be essential for survival under fluctuating environments. The knowledge we derive from the C. elegans studies should provide testable hypotheses in discovering similar mechanisms in higher animals.

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Age-related declines in motor function may be due, in part, to an increase in oxidative stress in the aging brain leading to dopamine (DA) neuronal cell death. In this study, we examined the neuroprotective effects of natural antioxidants resveratrol and pinostilbene against age-related DAergic cell death and motor dysfunction using SH-SY5Y neuroblastoma cells and young, middle-aged, and old male C57BL/6 mice. Resveratrol and pinostilbene protected SH-SY5Y cells from a DA-induced decrease in cell viability. Dietary supplementation with resveratrol and pinostilbene inhibited the decline of motor function observed with age. While DA and its metabolites (DOPAC and HVA), dopamine transporter, and tyrosine hydroxylase levels remain unchanged during aging or treatment, resveratrol and pinostilbene increased ERK1/2 activation in vitro and in vivo in an age-dependent manner. Inhibition of ERK1/2 in SH-SY5Y cells decreased the protective effects of both compounds. These data suggest that resveratrol and pinostilbene alleviate age-related motor decline via the promotion of DA neuronal survival and activation of the ERK1/2 pathways.

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We wished to determine whether L-DOPA, a common treatment for the motor deficits in Parkinson's disease, could also reverse the motor deficits that occur during aging. We assessed motor performance in young (2-3 months) and old (20-21 months) male C57BL/6 mice using the challenge beam and cylinder tests. Prior to testing, mice were treated with L-DOPA or vehicle. Following testing, striatal tissue was analyzed for phenotypic markers of dopamine neurons: dopamine, dopamine transporter, and tyrosine hydroxylase. Although the dopaminergic markers were unchanged with age or L-DOPA treatment, L-DOPA reversed the motor deficits in the old animals such that their motor coordination was that of a young mice. These findings suggest that some of the locomotor deficits that accompany normal aging are responsive to L-DOPA treatment and may be due to subtle alterations in dopaminergic signaling. KeywordsBehavior; dopamine; striatum Aging is usually accompanied by a decline in motor function, a phenomenon that can be observed in laboratory animals as well as in humans. For example, rodents typically exhibit a decline in spontaneous motor activity and motor coordination [1][2][3]7]. Such motor functions appear to be heavily influenced by the dopamine (DA) system [17]. One important piece of evidence for this conclusion comes from studies of Parkinson's disease (PD). In that condition, many of the motor deficits are strongly correlated with the loss of the DA neurons of the nigrostriatal projection [5].Corresponding author: Dr. Jane E. Cavanaugh, Department of Pharmacology, 455 Mellon Hall, Duquesne University, Phone: (412) 396-6358, Fax: (412) 396-4660, cavanaughj@duq.edu. * The first two authors contributed equally to this work.a) The authors have no actual or potential conflicts of interest. b) All animals were maintained in temperature-controlled rooms in the barrier facility maintained by the Division of Laboratory Animal Resources (DLAR) at the University of Pittsburgh. Animals were housed in accordance with Guidelines for the Care and Use of Animals, at 23°C with lights on between 1900 and 0700 hr. Animals were fed and watered ad libitum, and the woodchips in their cages changed every other day. Full-time trained animal care personnel performed all animal handling and maintenance. The director of the DLAR, a trained veterinarian, supervised animal care. All animal care was overseen by the Institutional Animal Care and Use Committee (IACUC).Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. L-DOPA, which increases the availability of DA in striatum, is able to temporarily impr...