Structural brain aging in inbred mice: potential for genetic linkage

To identify genetic factors involved in brain aging, we have initiated stud ies assessing behavioral and structural changes with aging among inbred mou se strains. Cognitive performance of C57BL/6J mice is largely maintained wi th aging, and stereological analysis revealed no significant age-related ch ange in neuron number, synaptic bouton number or glial number in the hippoc ampus. Moreover, no change in cortical neuron number and cholinergic basal forebrain neuron number has been found in this strain. 129Sv/J mice have mo re pronounced age-related cognitive deficits, although hippocampal and basa l cholinergic forebrain neuron number also appear unchanged with aging. Dif ferences in neurogenesis and neuron vulnerability in the adult CNS of C57BL /6, 129/Sv and other inbred strains have been reported, which in turn may h ave important consequences for brain aging. Age-related lesions, such as th alamic eosinophilic inclusions and hippocampal clusters of polyglucosan bod ies also vary greatly among inbred strains although the functional signific ance of these lesions is not clear. The continued assessment of such age-re lated structural and behavioral changes among inbred mouse strains offers t he potential to identify genes that control age-related changes in brain st ructure and function. (C) 2000 Elsevier Science Inc. All rights reserved.