Intranuclear rodlets in the substantia nigra: Interactions with marinesco bodies, ubiquitin, and promyelocytic leukemia protein

There is growing appreciation that the nucleus is organized into an array of discrete structural domains, each subserving a specific function. These functional nuclear bodies are to be distinguished from pathological intranuclear inclusions which have been described in a variety of neurodegenerative diseases. Marinesco bodies (MBs) are eosinophilic ubiquitinated intranuclear inclusions found in pigmented neurons of the human substantia nigra and locus coeruleus. Traditionally considered non-pathological entities, more recent studies have indicated that MBs are associated with the age-associated degenerative changes in the substantia nigra and striatal loss of dopaminergic terminals. In the present morphological study of the human substantia nigra, we demonstrate colocalization, contiguity, and focally shared immunoreactivity between MBs and neuronal intranuclear rodlets (INRs). The latter nuclear structures of uncertain function are markedly decreased in the cortex of Alzheimer's disease, but not dementia with Lewy bodies. In addition, we demonstrate an interaction between INRs and promyelocytic leukemia (PML) protein, the signature protein of PML nuclear bodies. These results suggest that structures which subserve the functional compartmentalization of the neuronal nucleus may be relevant to elucidating cellular mechanisms of age-related motor dysfunction.