Exercise Can Rescue Recognition Memory Impairment in a Model with Reduced Adult Hippocampal Neurogenesis

Running is a potent stimulator of cell proliferation in the adult dentate gyrus and these newly generated hippocampal neurons seem to be implicated in memory functions. Here we have used a mouse model expressing activated Ras under the direction of the neuronal Synapsin I promoter (named synRas mice). These mice develop down-regulated proliferation of adult hippocampal precursor cells and show decreased short-term recognition memory performances. Voluntary physical activity reversed the genetically blocked generation of hippocampal proliferating cells and enhanced the dendritic arborisation of the resulting doublecortin newly generated neurons. Moreover, running improved novelty recognition in both wild type and synRas littermates, compensating their memory deficits. Brain-derived neurotrophic factor (BDNF) has been proposed to be a potential mediator of physical exercise acting in the hippocampus on dentate neurons and their precursors. This was confirmed here by the identification of doublecortin-immunoreactive cells expressing tyrosine receptor kinase B BDNF receptor. While no difference in BDNF levels were detected in basal conditions between the synRas mice and their wild type littermates, running was associated with enhanced BDNF expression levels. Thus increased BDNF signalling is a candidate mechanism to explain the observed effects of running. Our studies demonstrate that voluntary physical activity has a robust beneficial effect even in mice with genetically restricted neurogenesis and cognition

Association of pre- and postoperative αKlotho levels with long-term remission after pituitary surgery for acromegaly

Soluble αKlotho (sKl) is a disease-specific biomarker that is elevated in patients with acromegaly and declines after surgery for pituitary adenoma. Approximately 25% of patients do not achieve remission after surgery, therefore a risk stratification for patients early in the course of their disease may allow for the identification of patients requiring adjuvant treatment. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) have been assessed as biomarker for disease activity, however the value of sKl as a predictive biomarker of surgical success has not been evaluated yet. In this study, we measured serum biomarkers before and after transsphenoidal pituitary surgery in 55 treatment-naïve patients. Based on biochemical findings at follow-up (7-16 years), we divided patients into three groups: (A) long-term cure (defined by normal IGF-1 and random low GH (< 1 μg/l) or a suppressed GH nadir (< 0.4/μg/l) on oral glucose testing); (B) initial remission with later disease activity; (C) persistent clinical and/or biochemical disease activity. sKl levels positively related to GH, IGF-1 levels and tumor volume. Interestingly, there was a statistically significant difference in pre- and postoperative levels of sKl between the long-term cure group and the group with persistent disease activity. This study provides first evidence that sKl may serve as an additional marker for surgical success, decreasing substantially in all patients with initial clinical remission while remaining high after surgery in patients with persistent disease activity

Untersuchungen zur Rolle des intrazellulären Signalproteins Ras in klinischer Depression und adulter hippocampaler Neurogenese im synRas-Mausmodell

Laut Neurotrophin-Hypothese wird dem BDNF (brain-derived neurotrophic factor) eine entscheidende Rolle in klinischer Depression und ihrer Behandlung zugesagt. Der Ras-übermittelte ERK-Signalweg (extracellular signal-regulated kinase cascade) wird als der bedeutendste BDNF/TrkB-vermittelte intrazelluläre Signalweg angesehen. Um die Rolle des BDNF/Ras/ERK-Signalwegs in der Wirkung von Antidepressiva und adulter Neurogenese zu untersuchen, wurden in dieser Arbeit transgene synRas-Mäuse verwendet. SynRas-Mäuse exprimieren konstitutiv aktiviertes humanes Ha-Ras in differenzierten Neuronen unter der Kontrolle des SynapsinI-Promotors. Die Ergebnisse zeigen, dass permanent aktiviertes Ras in differenzierten Neuronen von Mäusen auf verhaltensbiologischer als auch auf proteinbiochemischer Ebene ähnliche Effekte wie Antidepressiva erzielt. Weiterhin zeigen synRas-Mäuse Defizite in der adulten hippocampalen Neurogenese