Neuroscience
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Alzheimer's disease (AD) is a neurodegenerative disease mainly associated with aging, oxidative stress and genetic mutations. There are two pathological proteins involved in AD; Amyloid-β peptide and microtubule-associated protein Tau (MAPT). The β- and γ-secretase enzyme cleaves the Amyloid precursor protein, which results in the formation of extracellular plaques in brain. ⋯ The P2Y receptors give 'find me' or 'eat me' signals to microglia to either migrate or phagocytose cellular debris. Further, the actin cytoskeleton helps microglia to mediate directed chemotaxis and neuronal repair during neurodegeneration. Hence, we aim to emphasize the connection between purinergic signaling and actin-driven mechanical movements of microglia for migration and inflammation in AD.
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Growth cone-mediated axonal outgrowth and accurate synaptic targeting are central to brain morphogenesis. Translocation of the growth cone necessitates mechanochemical regulation of cell-extracellular matrix interactions and the generation of propulsive traction forces onto the growth environment. However, the molecular mechanisms subserving force generation by growth cones remain poorly characterized. ⋯ Analysis of F-actin retrograde flow reveals that Fmn2 functions as a clutch molecule and mediates the coupling of the actin cytoskeleton to the growth substrate, via point contact adhesion complexes. Using traction force microscopy, we show that the Fmn2-mediated clutch function is necessary for the generation of traction stresses by neurons. Our findings suggest that Fmn2, a protein associated with neurodevelopmental and neurodegenerative disorders, is a key regulator of a molecular clutch activity and consequently motility of neuronal growth cones.
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Effect of aging on daily rhythms of lactate metabolism in the medial prefrontal cortex of male mice.
Aging is associated with reduced amplitude and earlier timing of circadian (daily) rhythms in sleep, brain function, and behavior. We examined whether age-related circadian dysfunction extends to the metabolic function of the brain, particularly in the prefrontal cortex (PFC). Using enzymatic amperometric biosensors, we recorded lactate concentration changes in the PFC in Young (7 mos) and Aged (19 mos) freely-behaving C57BL/6N male mice. ⋯ Under constant conditions, the Aged rhythm showed a reduced amplitude not seen in the Young mice. We simultaneously observed a relationship between arousal state and PFC lactate rhythm via electroencephalography, which was modified by aging. Finally, using RT-qPCR, we found that aging affects the daily expression pattern of Glucose Transporter 1 (GLUT-1).
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Our aim was to identify the longitudinal changes in gray matter volume (GMV) and secondary alterations of structural covariance after pontine stroke (PS). Structural MRI and behavioral scores were obtained at 1 week, 1 month, 3 months, 6 months in 11 patients with PS. Twenty healthy subjects underwent the same examination only once. ⋯ Based on the CBE Crus II_IL and CBE Crus I_CL as seed regions, structural covariance analysis revealed that there were more positively and negatively correlated brain regions in PS group, mainly distributed in the bilateral prefrontal lobe, parietal lobe, temporal lobe, paralimbic system and cerebellum. In addition, PS group showed more additional correlations between these covariant brain regions, and the changes of GMV in these regions were correlated with behavioral scores related to motor and cognitive functions. These findings indicate that PS could lead to significant GMV atrophy in the bilateral cerebellar posterior lobe at the early stage, accompanied by anomalous structural covariance patterns with more covariant brain regions and additional structural connectivity, which may provide useful information for understanding the neurobiological mechanisms of behavioral recovery after PS.