Spinocerebellar ataxia type 3 (Machado-Joseph disease): severe destruction of the lateral reticular nucleus.
The lateral reticular nucleus (LRT) of the medulla oblongata is a precerebellar nucleus involved in proprioception and somatomotor automatisms. We investigated this nucleus in five individuals with clinically diagnosed and genetically confirmed spinocerebellar ataxia type 3 (SCA3, Machado-Joseph disease). Polyethylene glycol-embedded 100 micro m thick sections stained for lipofuscin granules and Nissl material as well as Nissl-stained paraffin-embedded sections revealed severe destruction of the LRT in all SCA3 brains examined. Some of the few surviving neurones contained ataxin-3-immunopositive intranuclear inclusion bodies, as noted in other affected brain regions in SCA3. Along with the severe neuronal depletion, obvious astrogliosis was seen in the LRT of all SCA3 patients. The findings suggest that the LRT is a consistent target of the pathological process underlying SCA3. In view of its afferent and efferent connections, destruction of the LRT probably contributes to gait ataxia in individuals suffering from SCA3.
Rüb
U
U
Department of Clinical Neuroanatomy, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, D-60590 Frankfurt/Main, Germany. u.rueb@em.uni-frankfurt.de
de Vos
R A I
RA
Schultz
C
C
Brunt
E R
ER
Paulson
H
H
Braak
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H
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D017827:Machado-Joseph Disease / Q000473:pathology*; D008297:Male; D008526:Medulla Oblongata / Q000473:pathology*; D008875:Middle Aged; D009410:Nerve Degeneration / Q000473:pathology; D009474:Neurons / Q000473:pathology; D012154:Reticular Formation / Q000473:pathology*