Early morphological changes of hereditary cerebellar cortical abiotrophy in rabbits.

We previously investigated the hereditary cerebellar cortical abiotrophy in littermates at postnatal day (PD) 25-31 delivered from a pair of rabbits. To estimate the onset time and incipient lesions associated with the cerebellar cortical abiotrophy of the cases, we mated the same pair again and examined early stages of the disease in F1 rabbit showing ataxia (PD 15), finding evidence that the ataxia is passed to subsequent generations via autosomal recessive inheritance. Clinical signs of the affected rabbit showed early-onset dysstasia and ataxia. The affected rabbit showed apoptotic granular cells before and after migration completion, degeneration (swelling) of parallel fiber terminals, abnormal junction (invaginated junction) of the parallel fiber-Purkinje cell synapses and irregular orientation of the Purkinje dendritic arbor in the molecular layer. Additionally, a reduced number of synaptic junctions between parallel fibers and Purkinje cells were detected, as well as at PD 25-31. Secondary changes, such as reduction or degeneration of Purkinje cells and granular cells were not yet observed at early stages. As synapse abnormality preceded the degeneration or reduction of Purkinje and granular cells at early stages, we concluded that the pathogenesis of the present cerebellar lesion was caused by failed synaptogenesis during postnatal cerebellar development.