TorsinA and B expression in the brain is detectable in human infants as young as four weeks old

Background: Mutations in torsinA underlie familial, early onset, generalized torsion dystonia, the most common and severe primary dystonia with symptoms starting in the first decade. The torsins comprise a four member family of AAA+ chaperone proteins, including torsinA, torsinB, torp2A and torp3A in humans. TorsinB protein and torsinA are highly homologous and located in the endoplasmatic reticulum and nuclear envelope in cultured cells. Co-precipitation and double labelling studies suggest that they may carry out related functions in vivo. However the expression pattern of torsinB in the developing brain has not been studied so far.

Objective: To study the spatial and temporal expression of torsinB in addition to torsinA in the developing brain.

Methods: Four different brain regions (cerebellum, basal ganglia, substantia nigra, hippocampus) of 15 subjects without histopathological evidence of brain injury (age 20 weeks of gestation up to 7 years) were studied by detailed immunohistochemistry with different antibodies against torsinA and B in addition to Western blot and peptide blocking studies.

Results: Expression of torsinB and torsinA was detectable at age one month in particular in the midbrain and cerbellum and did increase in intensity until the age of three years. In contrast to torsinA, which evenly stains the cytoplasm of neurons, torsinB is primarily restricted to the perinuclear area and the nuclear envelope. In addition both proteins are also detectable in axons and neuropil.

Conclusion: Our results indicate that TorsinA and B protein expression are temporarily regulated in a similar fashion supporting the hypothesis that they may carry out related functions in vivo.