54 research outputs found
Brain serotonin critically contributes to the biological effects of electroconvulsive seizures
Compounds targeting serotonin (5-HT) are widely used as antidepressants. However, the role of 5-HT in mediating the effects of electroconvulsive seizure (ECS) therapy remains undefined. Using Tph2(-/-) mice depleted of brain 5-HT, we studied the effects of ECS on behavior and neurobiology. ECS significantly prolonged the start latency in the elevated O-Maze test, an effect that was abolished in Tph2(-/-) mice. Furthermore, in the absence of 5-HT, the ECS-induced increase in adult neurogenesis and in brain-derived neurotrophic factor signaling in the hippocampus were significantly reduced. Our results indicate that brain 5-HT critically contributes to the neurobiological responses to ECS
APP Intracellular Domain Impairs Adult Neurogenesis in Transgenic Mice by Inducing Neuroinflammation
A devastating aspect of Alzheimer's disease (AD) is the progressive deterioration of memory due to neuronal loss. Amyloid precursor protein (APP) occupies a central position in AD and APP-derived amyloid-β (Aβ) peptides are thought to play a pivotal role in disease pathogenesis. Nonetheless, it is becoming clear that AD etiology is highly complex and that factors other than Aβ also contribute to AD pathogenesis. APP intracellular domain (AICD) is generated together with Aβ and we recently showed that AICD transgenic mice recapitulate pathological features of AD such as tau hyperphosphorylation, memory deficits and neurodegeneration without increasing the Aβ levels. Since impaired adult neurogenesis is shown to augment memory deficits in AD mouse models, here we examined the status of adult neurogenesis in AICD transgenic mice.We previously generated transgenic mice co-expressing 59-residue long AICD fragment and its binding partner Fe65. Hippocampal progenitor cell proliferation was determined by BrdU incorporation at 1.5, 3 and 12 months of age. Only male transgenic and their respective wilt type littermate control mice were used. We find age-dependent decrease in BrdU incorporation and doublecortin-positive cells in the dentate gyrus of AICD transgenic mice suggesting impaired adult neurogenesis. This deficit resulted from decreased proliferation and survival, whereas neuronal differentiation remained unaffected. Importantly, this impairment was independent of Aβ since APP-KO mice expressing AICD also exhibit reduced neurogenesis. The defects in adult neurogenesis are prevented by long-term treatment with the non-steroidal anti-inflammatory agents ibuprofen or naproxen suggesting that neuroinflammation is critically involved in impaired adult neurogenesis in AICD transgenic mice.Since adult neurogenesis is crucial for spatial memory, which is particularly vulnerable in AD, these findings suggest that AICD can exacerbate memory defects in AD by impairing adult neurogenesis. Our findings further establish that AICD, in addition to Aβ, contributes to AD pathology and that neuroinflammation plays a much broader role in AD pathogenesis than previously thought
Premodern debasement: a messy affair
The paper argues that in premodern Europe, the practice of debasement was far more ‘messy’ than research has generally recognised. First, high information costs often prevented the effective control of mint officials who could exploit their resulting autonomy in order to debase coins on their own account. Second, these costs made it impossible to monitor markets closely enough to enforce regulations. Attempts by governments to debase coins by increasing their nominal value therefore ‘worked’ only if they conformed to the market rates of these coins. Finally, high information costs prevented the creation of closed areas where the domestic currency enjoyed a monopoly. The resulting trade in coinage created incentives for governments to issue inferior copies of their neighbour’s coins – a practice that had the same consequences as a debasement – and forced the affected governments to follow suit by debasing their own coinage, too
Functional anatomy of 5-HT2A receptors in the amygdala and hippocampal complex: relevance to memory functions
Hidden Costs: Understanding the Financial Implications of Incentivizing Full-Time Enrollment among Community College Students
Differential Distribution by Size of Layer V Pyramidal Neurons in Raccoon (Procyon lotor) Sensorimotor Cortex 1,2
THE ROLE AND POTENTIAL USE OF LAND SETTLEMENTS IN DEVELOPMENT POLICIES: LESSONS FROM PAST EXPERIENCE
Soluble amyloid precursor protein-α rescues age-linked decline in neural progenitor cell proliferation
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