Neuropathological studies in a mutant hamster model of paroxysmal dystonia

Abstract

Dystonic movements in a mutation of the Syrian golden hamster, named dtsz, have several features in common with clinically observed paroxysmal dystonic choreoathetosis. In this study the CNS of the mutant hamsters and age-matched nondystonic controls was examined for morphological alterations at the age of 30 days, i.e., when the severity of the dystonic syndrome is fully developed. Particular interest was directed to those brain regions (caudate nucleus, putamen, globus pallidus, ventrolateral thalamus) that are presumably involved in symptomatic dystonia of humans, as well as to regions (e.g., spinal cord, dorsal root ganglia, nucleus ruber) for which neuropathologically detectable lesions have been found previously in the dystonia musculorum mouse. The neuropathological investigation was carried out on routine paraffin histology on step sections of the whole brain and spinal cord. In addition, a silver impregnation method was used for detection of pre- and/or postsynaptic degeneration. Light microscopic examination, including morphometry, of the nervous tissue failed to reveal any morphological or morphometric differences between control and dystonic hamsters. The only abnormality that was found in several control and dystonic hamsters was hydrocephalus. Breeding studies using magnetic resonance imaging for detection of hydrocephalus showed that hydrocephalus was hereditary but not related to dystonia. Virus infections as a cause of hydrocephalus or dystonia could be excluded by serological analysis with determinations of various virus antibodies in hamster sera. The lack of neuropathological alterations related to dystonic movements in the present study in dtsz hamsters is comparable to most cases of human hereditary or idiopathic dystonia, which show dystonic movements in the absence of morphological alterations.

Hereditary hydrocephalus internus in a laboratory strain of golden hamsters (Mesocricetus auratus)

“…After Yoon and Slaney (1972), Wahnschaffe et al (1990) and Edwards et al (2006), we report a hereditary hydrocephalus in golden hamsters. Several mutations in mice are associated with the occurrence of hydrocephalus (reviewed by Jones et al, 2000).…”

“…This mutation was linked with cream coat color (Yoon and Peterson, 1977). Wahnschaffe et al (1990) claimed that hydrocephalus in golden hamsters was inherited like an autosomal recessive trait without presenting data on it. This mutation was detected by coronal brain sections and did not induce apparent symptoms (Wahnschaffe et al, 1990).…”

“…Wahnschaffe et al (1990) claimed that hydrocephalus in golden hamsters was inherited like an autosomal recessive trait without presenting data on it. This mutation was detected by coronal brain sections and did not induce apparent symptoms (Wahnschaffe et al, 1990). Therefore, it is likely a different mutation from the one Yoon and Slaney (1972) described and resembled our cases.…”

“…Alternatively, the distinction between no and mild hydrocephalus by the pathologists might not have been accurate enough. Since the study of Wahnschaffe et al (1990) was done in the US in the end of the 1980s, this relatively benign mutation could be deeply embedded in this strain worldwide. The absence of an easy diagnosis in live animals will prevent the elimination of the incidence of hydrocephalus in this strain.…”

Animal models of generalized dystonia

“…Upon gross histological examination, the dt sz hamster brain appears relatively normal. 14 However, a reduction in parvalbumin immunoreactivity is observed throughout the dt sz hamster striatum, suggesting a marked deficit in the number of GABAergic interneurons and implicating the basal ganglia as the source of dystonic attacks. 15 Pharmacological findings further support the notion of aberrant basal ganglia GABAergic neurotransmission as a factor in the dt sz hamster disease pathogenesis.…”