The Reelin Receptors Apoer2 and Vldlr Coordinate the Patterning of Purkinje Cell Topography in the Developing Mouse Cerebellum

The adult cerebellar cortex is comprised of reproducible arrays of transverse zones and parasagittal stripes of Purkinje cells. Adult stripes are created through the perinatal rostrocaudal dispersion of embryonic Purkinje cell clusters, triggered by signaling through the Reelin pathway. Reelin is secreted by neurons in the external granular layer and deep cerebellar nuclei and binds to two high affinity extracellular receptors on Purkinje cells-the Very low density lipoprotein receptor (Vldlr) and apolipoprotein E receptor 2 (Apoer2). In mice null for either Reelin or double null for Vldlr and Apoer2, Purkinje cell clusters fail to disperse. Here we report that animals null for either Vldlr or Apoer2 individually, exhibit specific and parasagittally-restricted Purkinje cell ectopias. For example, in mice lacking Apoer2 function immunostaining reveals ectopic Purkinje cells that are largely restricted to the zebrin II-immunonegative population of the anterior vermis. In contrast, mice null for Vldlr have a much larger population of ectopic Purkinje cells that includes members from both the zebrin II-immunonegative and -immunopositive phenotypes. HSP25 immunoreactivity reveals that in Vldlr null animals a large portion of zebrin II-immunopositive ectopic cells are probably destined to become stripes in the central zone (lobules VI–VII). A small population of ectopic zebrin II-immunonegative Purkinje cells is also observed in animals heterozygous for both receptors (Apoer2+/−: Vldlr+/−), but no ectopia is present in mice heterozygous for either receptor alone. These results indicate that Apoer2 and Vldlr coordinate the dispersal of distinct, but overlapping subsets of Purkinje cells in the developing cerebellum

Psychiatric symptoms in alcoholics attending outpatient treatment

The importance of psychiatric symptomatology for the treatment course of alcoholics was analyzed in a long-term outpatient treatment study. Seventy-two patients, 60 men and 12 women, were personally interviewed during treatment and after 3 years. Before treatment psychiatric symptoms were rated according to the Comprehensive Psychopathological Rating Scale (CPRS). Women had significantly higher scores than men. Men with many symptoms and women had more psychological benefits from drinking and a more impaired personality structure than men with few symptoms. Men with many symptoms also had a lower level of social functioning. The severity of abuse did not differ between the three groups. Men with many symptoms had a less favorable outcome between 25 and 36 months after start of treatment than men with few symptoms and women. Among men who completed treatment, those with many symptoms showed a less successful course after 6 months and during the 3rd year after start of treatment, while differences after 3 months and during later stages of treatment were less pronounced. It is suggested that before start of treatment a psychiatric evaluation should be performed including psychiatric diagnosis, personality analysis, and an assessment of psychological benefits from drinking