Occipital cortex ablation in adult rat causes retrograde neuronal death in the lateral geniculate nucleus that resembles apoptosis

Abstract

The mechanisms of retrograde neurodegeneration following axotomy and target deprivation in the adult central nervous system remain poorly understood. We used a unilateral occipital cortex ablation model in adult rats to test the hypothesis that retrograde neurodegeneration in the dorsal lateral geniculate nucleus resembles apoptosis. Using the retrograde tracer Fluorogold, combined with nuclear dyes or the terminal transferase-mediated deoxyuridine triphosphate-biotin nick end labeling method for detecting nuclear DNA fragmentation, apoptotic geniculocortical projection neurons were identified at approximately. six to seven days postlesion. Degeneration of dorsal lateral geniculate neurons was characterized by aberrant accumulation of perikaryal non-phosphorylated neurofilaments and, ultrastructurally, by early vacuolation and subsequent swelling of dendrites. Ultrastructural alterations in the perikaryon of dying dorsal lateral geniculate neurons included the classic chromatolytic response, with redistribution of the rough endoplasmic reticulum and dispersion of free ribosomes followed by fragmentation of the rough endoplasmic reticulum, as well as dilatation and vesiculation of the Golgi, and accumulation of intact mitochondria. Subcellular alterations evolved into classic apoptotic changes, including progressive cytoplasmic and nuclear condensation with chromatin compaction into uniformly large round clumps, while the morphological integrity of mitochondria was preserved until late in the progression of neuronal death. Cytoplasmic and then nuclear fragments budded into the surrounding neuropil and were engulfed by oligodendrocytes. We conclude that the retrograde neurodegeneration of geniculocortical neurons in adult brain results in neuronal death which has a phenotype that closely resembles apoptosis. The morphological changes that occur during this process progress from chromatolysis through consecutive stages associated with apoptosis.