Colony-forming ectopic granule cells in the cerebellar primary fissure of normal adult rats: a morphologic and morphometric study

The morphology and degree of maturation of intrafissural colony-forming ectopic granule cells (EGCs) were investigated in the cerebella of normal adult rats. These EGCs exhibit a notable degree of morphological maturity, with 2-5 short dendrites radiating from a globular soma, typical dendritic claw-like terminals and descending axons. The EGCs receive the afferent input of mossy fiber terminals and their axons also establish homologous synapses with the postsynaptic dendritic spines of the Purkinje cells. Although these EGCs exhibit the typical morphology of mature granule cells, the morphometric analysis shows, however, a significant reduction in the number of dendrites (mean 3.30 +/- 0.60) and 'claws' (mean 3.66 +/- 0.12) in the EGCs with respect to the controls (mean 3.85 +/- 0.73 and 4.53 +/- 0.13, respectively). These differences may be indicative of a slight numerical mismatching between EGCs and afferent mossy fibers, which limit the input that the ectopic neurons receive. The karyometric study also showed that the average nuclear area in EGCs was significantly smaller (mean 19.38 +/- 0.24 micron2) than in controls (mean 21.88 +/- 0.24 micron2), suggesting a positive correlation between nuclear size and the number of postsynaptic dendritic terminals available in the granule cells. The influence of some morphogenetic factors on the degree of maturity attained by these ectopic neurons is discussed, particularly the interactions of mossy fibers and astrocytes with maturing EGCs.     

Novel mutation of SACS gene in a Spanish family with autosomal recessive spastic ataxia.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an inherited neurodegenerative disorder characterized by early-onset, spastic ataxia and peripheral neuropathy. It was originally described in an inbred population of Quebec and later in some other countries. We report a new missense SACS mutation (7848C>T) in a Spanish family whose phenotype is similar to that of the previously described ARSACS patients. 7848C>T is the first SACS mutation reported in Spain confirming worldwide distribution of the disease.     

The insulin-like growth factor I system in cerebellar degeneration

Brain insulin-like growth factor I (IGF-I) and its related molecules may be involved in neurodegenerative processes in which IGF-I-containing pathways are compromised. Since IGF-I is present in the olivocerebellar circuitry, two types of late-onset cerebellar ataxias (olivopontocerebellar and idiopathic cerebellar cortical atrophy) were chosen to test this hypothesis. The following significant changes in the peripheral IGF-I system of these patients were found: low IGF-I levels, and high IGF-binding protein 1 (BP-1), and BP-3 affinity for IGF-1. Sixty percent of the patients also had significantly low insulin levels. Patients suffering from other neurological diseases with cerebellar dysfunction and ataxia not involving the olivocerebellar pathway also had low IGF-I levels, while IGFBPs and insulin levels were normal. Our data indicate that degeneration of an IGF-I-containing neuronal pathway produces significant changes in the peripheral IGF system. This suggests strongly that the endocrine (bloodborne) and the paracrine/autocrine (brain) IGF systems are linked functionally. We propose that alterations in the blood IGF-I system may constitute a marker of some cerebellar diseases.     

Spinocerebellar ataxia type 2 with Levodopa-responsive parkinsonism culminating in motor neuron disease.

We describe an exceptional spinocerebellar ataxia type 2 (SCA2) phenotype combining cerebellar ataxia, levodopa-responsive parkinsonism, and motor neuron symptoms. We conclude that motor neuron symptoms and signs may be a striking manifestation in SCA2, masking pre-existing cerebellar and extrapyramidal semeiology.