Pallido-nigral spheroids in nonhuman primates: accumulation of heat shock proteins in astroglial processes.

Alpha-B crystallin, ubiquitin and heat shock protein 27 (hsp27) belong to a class of proteins that are overexpressed in response to pathological conditions associated with increased cellular stress. In the present study, brain sections of old rhesus monkeys ( Macaca mulatta; n=10; mean age, 29.4 years) and baboons ( Papio anubis; n=8; mean age, 18.3 years) were examined for ubiquitin, alpha-B crystallin and hsp27-immunopositive structures. In both species, immunoreactive spheroid-like bodies were found in the globus pallidus and in the substantia nigra, pars reticulata. These structures frequently were associated with abnormally swollen cellular processes. To further clarify the origin of the pallido-nigral spheroids, single- and double-immunostaining was performed for hsp27, alpha-B crystallin and the astroglial marker glial fibrillary acidic protein (GFAP) as well as for neuronal markers against neurofilament and dendritic microtubule-associated protein 2. Confocal microscopic analysis demonstrated that spheroids were localized in swollen astroglial processes, whereas they were not seen in neuronal structures. Thus, pallido-nigral spheroids can be classified as astroglial accumulations of heat shock proteins. Further investigations of these structures may provide information pertinent to our understanding of astroglial heat shock protein inclusions developing in degenerative human brain diseases.

Intranuclear aggregation of nonexpanded ataxin-3 in marinesco bodies of the nonhuman primate substantia nigra.

Marinesco bodies (MB) are intranuclear inclusion bodies predominantly found in melanin-pigmented neurons of the substantia nigra. MB are demonstrable not only in humans but also in nonhuman primates. In the present study MB of aged rhesus monkeys (Macaca mulatta; n = 15; mean age 16 years) and aged baboons (Papio anubis; n = 13; mean age 25 years) were examined immunohistochemically. MB were found to be immunoreactive for ubiquitin, a protein involved in initiation of proteasome-mediated proteolysis. We also demonstrate that MB in monkeys are intensely immunoreactive for the protein ataxin-3 as detected by using two monoclonal anti-ataxin-3 antibodies (1H9 and 2B6). The abnormally expanded form of this polyglutamine protein is known to be causally involved in spinocerebellar ataxia type 3 or Machado-Joseph disease. The monoclonal antibody 1C2 was employed to examine whether ataxin-3 in MB in monkeys contains such an abnormally expanded polyglutamine stretch. MB were consistently 1C2-immunonegative, indicating that they are composed of normal wild-type ataxin-3. In conclusion MB in nonhuman primates permit experimental examination of mechanisms involved in transnuclear localization, intranuclear aggregation, and ubiquitination of nonexpanded polyglutamine proteins.