Lewy bodies are filamentous neuronal inclusions characteristic of
Parkinson's disease, and
neurofilament triplet proteins are the major components of the filaments in Lewy bodies. Since the
neurofilament proteins found in Lewy bodies are abnormally phosphorylated and partially degraded, the formation of Lewy bodies may be due to the defective metabolism of these
proteins, and this could lead to impairments in the structure and function of neurofilament rich neuronal processes (i.e., large caliber axons). To gain further insights into the metabolism of neurofilaments in
Parkinson's disease, we evaluated neurofilament
mRNA levels by semi-quantitative in situ hybridization histochemistry in postmortem tissues from
Parkinson's disease and control subjects. Substantia nigra pars compacta neurons were examined with
digoxigenin-
UTP labeled
cRNA probes to the heavy and light neurofilament mRNAs. The relative abundance of these mRNAs was measured by videodensitometric image analysis of chromogenic reaction product. Using this approach, we demonstrated that the levels of both heavy and light neurofilament mRNAs were reduced in
Parkinson's disease substantia nigra pars compacta neurons. Additionally, the levels of heavy neurofilament
mRNA were lowest in Lewy body containing neurons in the
Parkinson's disease cases. These results suggest that the formation of neurofilament-rich Lewy bodies in substantia nigra pars compacta neurons is associated with reduced levels of the heavy and light neurofilament mRNAs in
Parkinson's disease. Thus, it is possible that the accumulation of abnormal
neurofilament proteins in Lewy bodies and diminished neurofilament mRNAs contribute to the degeneration of substantia nigra pars compacta neurons in
Parkinson's disease.