Decreased medial entorhinal cortical thickness in olanzapine exposed female rats is not ameliorated by exercise.

Aerobic exercise has been associated with hippocampal plasticity, both in healthy adults and in psychosis patients, but its impact on cortical regions remains unclear. The entorhinal cortex serves as a critical gateway for the hippocampus, and recent studies suggest that this region may also be impacted following an exercise regime. In order to investigate the effects of antipsychotic medications and exercise on the entorhinal cortex, female rats were chronically administered either olanzapine or vehicle and were either sedentary or had access to a running wheel for 9 weeks. Olanzapine-treated rats had decreased medial entorhinal cortical thickness compared to vehicle-treated rats. A statistically significant interaction was observed for layer II of the entorhinal cortex, with exercising rats having significantly greater thickness compared to sedentary rats in the vehicle group, but not the olanzapine group. Greater total entorhinal and lateral entorhinal cortical thickness was associated with greater average activity. In exercising rats, decreasing glucose intolerance was associated with larger total entorhinal and layer II cortical thickness. Lower fasting insulin levels were associated with greater total entorhinal, lateral entorhinal, and layer II cortical thickness. The relationship between increased activity and greater entorhinal cortical thickness was mediated by reduced fasting insulin, indicating that regulation of metabolic risk factors may contribute to impact of aerobic exercise on the entorhinal cortex. Aerobic exercise may be helpful in counteracting metabolic side effects of antipsychotic medications and managing these side effects may be key to promoting entorhinal cortical plasticity in patients treated with second-generation antipsychotic drugs.

Effects of chronic exercise and treatment with the antipsychotic drug olanzapine on hippocampal volume in adult female rats.

Numerous studies have reported that the hippocampus in schizophrenia patients is reduced in volume compared to the normal population. Antipsychotic medications have had mixed benefits in maintaining hippocampal volume or reversing volume loss. Recent evidence indicates that routine aerobic exercise represents a promising intervention for reversing hippocampal loss and cognitive deficits. In the present study, we measured the effects of chronic treatment with olanzapine and daily exercise on the hippocampal volumes of rats. Adult female rats were treated during the week with either olanzapine (10mg/kg) or vehicle for 9 consecutive weeks. Subgroups of animals were provided access to exercise running wheels for 1 or 3h per day during the same period, or were sedentary. Metabolic indices, including glucose tolerance, were measured on a weekly basis. At the conclusion of the study, brains were perfused and hippocampal sections were Nissl stained. Total hippocampal volume was measured using the Cavalieri estimator. Treatment with olanzapine caused a significant decrease in hippocampal volume in sedentary rats. However, exercise was able to reverse most of this volume loss. The hippocampal sub-regions of the dentate gyrus and CA1 were most strongly affected by olanzapine and exercise. Of interest, there was a strong and highly significant negative correlation between glucose intolerance and hippocampal volume, whereby greater glucose intolerance was associated with a smaller hippocampal volume. These findings indicate that exercise may have beneficial effects on the hippocampus when antipsychotic medication can contribute to changes in volume.

A multicentric study of 41 cases of B-prolymphocytic leukemia: two evolutive forms.

B-prolymphocytic leukemia (B-PLL) is an infrequent disease with a poor prognosis. We present the clinical and biological features of 41 patients. Median age was 67 years [42-89] and male-female sex ratio was 2.4. The immunophenotyping revealed B-cell phenotype, with a high level expression of surface IgM and/or IgD in all cases, FMC7+ in 76 % of cases and CD5+ in 67%. Marked spontaneous in-vitro apoptosis was observed in most cases tested (n = 12). The median overall survival time was 5 years and the event-free survival time was 37 months. As detected by univariate and multivariate analysis, the only variables associated with a poor prognosis were advanced age and anemia. No significant difference was observed between de novo PLL (n = 27) and prolymphocytoid transformation of chronic lymphocytic leukemia (n = 14). Two groups of patients were individualized according to their clinical course: patients who died within one year of diagnosis (n = 14) and patients who had a prolonged survival (n = 23) without any treatment in some cases. The comparison between the 2 groups showed that they differed in age (p = 0.01) and anemia (p = 0.02). We also observed that the patients with p53 mutations had a worse clinical outcome. Taken together these data confirm that B-PLL should be regarded as a distinct form of chronic lymphoproliferative disorder and suggest the existence of two patterns of clinical evolution.