title: The putative role of free radicals in the loss of neuronal functioning in senescence.
abstract: One of the hallmarks of the aging process is a loss of sensitivity in central neuronal receptors to agonist stimulation. This appears to be especially true in central (hippocampal, striatal) muscarinic cholinergic systems and in the striatal dopamine systems. For these two systems, any decline in their sensitivity can be of extreme importance in determining the behavioral capabilities of the organism. Decrements in the striatal dopamine system may be reflected as motor behavioral deficits, while the central cholinergic systems play a major role in the processing of memory through the activation of muscarinic receptors (mAChR). Declines in the function of these receptors appear to be at least partially responsible for the marked deterioration of cognitive function in normal aging and, more notably, in Alzheimer's disease (AD). Previous work has indicated only minimal success in improving performance in tasks that assess memory in senescent animals or humans with pharmacological agents which enhance cholinergic functioning. The present review describes research that indicates that two of the factors involved in this decline in receptor sensitivity include: (a) decreased receptor concentrations and (b) age-related decrements in signal transduction pathways. Studies are reviewed that indicate that the oxidative neural damage that occurs via kainic acid or ionizing radiation parallel those seen in aging. It is suggested that the common mechanism that may exist among all of the age-, disease-, excitatory amino acid- or radiation-induced deficits in neuronal transmission may involve free-radical-mediated alterations in membrane integrity through lipid peroxidation.
authors.affiliation: Molecular Physiology and Genetics Section, Francis Scott Key Medical Center, Baltimore, MD 21224.
authors.forename: J A
authors.initials: JA
authors.lastname: Joseph
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D005609:Free Radicals; D006801:Humans; D009474:Neurons / Q000502:physiology*
chemical_list: D005609:Free Radicals