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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Social bonds such as parent-infant attachment or pair bonds can be critical for mental and physical well-being. The monogamous prairie vole (Microtus ochrogaster) has proven useful for examining the neural substrates regulating social behaviors, including social bonding. Oxytocin (OXT) and oxytocin receptor (OXTR) play critical roles in alloparental care, pair bonding and consoling behavior in prairie voles. ⋯ We found enhanced green fluorescent protein (EGFP) positive neurons in anterior olfactory nucleus, PFC, ACC, insular cortex (IC), paraventricular thalamus (PVT), basolateral amygdala (BLA), and posteromedial and posterolateral cortical amygdaloid area (PMCo, PLCo). The ACC to NAcc OXTR projection may represent a species-specific circuit since Oxtr-expressing neurons in the ACC of mice were reported not to project to the NAcc. This is the first delineation of Oxtr-expressing neural circuits in the prairie vole, and demonstrates the utility of this novel genetically modified organism for characterizing OXTR circuits involved in social behaviors.
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The effects of systemic inflammation on the pathogenesis of Alzheimer's disease (AD) are not clarified, both beneficial and deleterious effects being reported. Allergy is accompanied by a systemic inflammatory response and some epidemiological studies have reported a positive association between a history of allergy/asthma and dementia. To investigate whether chronic airway allergy influences the inflammatory status in the brain, AD-like pathology, and behaviour in relation to AD, we induced chronic airway allergy in triple transgenic AD (3xTgAD) and wildtype (WT) mice by repeated exposure to ovalbumin (OVA) as allergen. ⋯ In contrast, allergy increased the levels of interleukin (IL)-1β and complement component 1q (C1q) in WT mice. Bronchoalveolar lavage fluid analysis confirmed eosinophilia in both genotypes, but the basal levels of eosinophils were lower in 3xTgAD mice. In summary, allergy induced predominantly anti-inflammatory effects in 3xTgAD mice, and pro-inflammatory effects in WT mice, thus being another potential factor to be considered when studying AD pathogenesis.