Brain research
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Neuritic dystrophy with amyloid burden and neurofibrillary tangles are pathological hallmarks of Alzheimer's disease. Genetic disruption of CD40 or CD40L alleviates amyloid burden, astrocytosis, and microgliosis in transgenic animal models of Alzheimer's disease. It has been reported that phosphorylated tau-positive dystrophic neurites are observed in transgenic mice over-expressing human mutant beta-amyloid precursor protein (Tg2576). ⋯ Further, we show that CD40L or CD40 deficiency reduces the mean ratio of dystrophic neurite area to congophilic plaque area and the level of expression of cdk5 and p35/p25 in mice. In addition, we show that in a human neuroblastoma cell line treated with CD40L, cdk5 and p35/p25 are increased. Together, our data suggest that CD40-CD40L interaction has an effect on tau phosphorylation independent of beta-amyloid pathology, and that this effect may occur through a decrease of cdk5 and p35/p25.
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It is well known that prior experience to the elevated plus-maze increases the avoidance of rodents to the open arms and impairs the anxiolytic-like effect of benzodiazepines evaluated during a subsequent exposure to the maze, a phenomenon known as "one-trial tolerance". Centrally injected benzodiazepine drugs attenuate anxiety in some limbic structures, such as hypothalamus, amygdala and the midbrain periaqueductal gray (PAG). This study investigated the effects of intra-PAG infusions of midazolam (MDZ) in maze-naïve and maze-experienced mice. ⋯ The antiaversive effects of MDZ were completely blocked by prior injection of flumazenil which in turn did not alter any other behavioral measure. In maze-experienced mice, intra-PAG infusion of MDZ did not modify any behavioral measure. Taken together, present results corroborate previous studies demonstrating that GABA/benzodiazepine receptor complex located within the PAG plays a role on anxiety modulation in maze-naïve mice as well as indicate its involvement in the OTT phenomenon.
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Changes in the partial pressure of arterial CO2 (PaCO2) regulates cerebrovascular tone and dynamic cerebral autoregulation (CA). Elevations in PaCO2 also increases autonomic neural activity and may alter the arterial baroreflex. We hypothesized that hypercapnia would impair, and hypocapnia would improve, dynamic CA and that these changes would occur independently of any change in baroreflex sensitivity (BRS). ⋯ Hypercapnia caused a progressive increase in PaCO2 and MCAv whereas hypocapnia caused the opposite effect. Despite marked changes in CPP, there were no evident change in transfer-function gain, coherence, MAP variability or BRS; however, both MCAv variability and phase in the very-low frequency range was reduced during the most severe level of hyper- and hypocapnia (P < 0.05), and were related to elevations in ventilation (R2 = 0.42-0.52, respectively; P < 0.001). It seems that hyperventilation, rather than PaCO2, has an important influence on dynamic CA.
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Neurite (axon and dendrite) degeneration requires self-destructive programs independent of cell death programs to segregate neurite degeneration from cell soma demise. We have here addressed the question of whether neuritic degeneration is delayed or occurs normally under conditions in which sympathetic neurons acquire resistance to somal apoptosis upon maturation. For this purpose, we have examined both beading formation and fragmentation, two hall-marks of neurite degeneration, caused by three experimental paradigms including NGF deprivation, treatment with microtubule-disrupting agents, and in vitro Wallerian degeneration. ⋯ Neuritic ATP levels of young ganglia decreased rapidly, while those of mature ganglia did so slowly during degeneration, although the basal levels of neuritic ATP of both ganglia were similar. Notably, mature neurites were resistant to fragmentation caused by NGF deprivation and capable of growing again after replenishment of NGF. This development of resistance to neurite degeneration in mature neurons may be thought as an important protective mechanism for the maintenance of the adult nervous system.
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The behavioral manifestations of autism, including reduced sociability (reduced tendency to seek social interaction), may be related to underdevelopment of the corpus callosum (CC). The BALB/cJ inbred mouse strain is a useful model system for testing the relationship between reduced sociability and CC underdevelopment. BALB/cJ mice show low levels of sociability, on average, but substantial intrastrain variability in sociability, as well as striking variability in CC development. ⋯ C57BL/6J mice showed consistently high levels of sociability and normal corpus callosum development. These results suggest that abnormal white matter structure is associated with deficits in sociability in BALB/cJ mice. Additional studies are warranted to elucidate the relationship between brain connectivity and sociability in this model system.