ABSTRACT
Persons with Alzheimer's disease (AD) have progressive reductions in the relative sizes of the corpus callosum and hippocampus. Homozygotic PDAPP transgenic mice over-expressing a mutant form of the human amyloid precursor protein have more pronounced reductions in these regions, which are apparent prior to the deposition of amyloid plaques and do not progress with advancing age. The length of the corpus callosum was reduced by two-thirds, the fornix commissure was negligible, and the hippocampal volume was reduced by one-third, suggesting a massive disconnection between the cerebral hemispheres and the hippocampi in PDAPP mice. These findings, which might account for the early, nonprogressive behavioral abnormalities observed in these animals, have implications for the study of AD.
Subject(s)
Alzheimer Disease/pathology , Amyloid beta-Protein Precursor/genetics , Corpus Callosum/pathology , Fornix, Brain/pathology , Hippocampus/pathology , Alzheimer Disease/genetics , Amino Acid Substitution , Animals , Disease Models, Animal , Male , Mice , Mice, TransgenicABSTRACT
The subependymal zone (SEZ) of the adult mammalian forebrain contains a population of progenitor cells that proliferate in response to brain injury. This study examined the effect of cortical injury on metabolic activity in the SEZ using quantitative histochemistry of cytochrome oxidase. The SEZ showed significantly enhanced cytochrome oxidase activity in rats with electrolytic cortical injuries relative to sham-operated controls, while other brain regions showed no such changes. The results indicate that the SEZ had increased oxidative energy demands, and thus provide metabolic evidence that SEZ cells are activated in response to brain injury.
