Neuroscience
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G-protein-coupled receptors (GPCRs) are shown to be involved in Alzheimer's disease (AD) pathogenesis. However, because GPCRs include a large family of membrane receptors, it is unclear which specific GPCR or pathway with rational ligands can become effective therapeutic targets for AD. ⋯ Because amylin shares a similar secondary structure with amyloid-β peptide (Aβ), I propose that the AmR/GPCR pathway is disturbed by a large amount of Aβ in the AD brain, leading to tau phosphorylation, neuroinflammation and neuronal death in the pathological cascade. Amylin-type peptides, readily crossing the blood-brain barrier (BBB), are the rational ligands to enhance this GPCR pathway and may exhibit utility as novel therapeutic agents for treating AD.
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During the last few years, rich-club (RC) organization has been studied as a possible brain-connectivity organization model for large-scale brain networks. At the same time, empirical and simulated data of neurophysiological models have demonstrated the significant role of intra-frequency and inter-frequency coupling among distinct brain areas. The current study investigates further the importance of these couplings using recordings of resting-state magnetoencephalographic activity obtained from 30 mild traumatic brain injury (mTBI) subjects and 50 healthy controls. ⋯ Additionally, mTBI and control subjects can be correctly classified with high accuracy (98.6%), whereas a general linear regression model can effectively predict the subject group using the ratio of type I and type II coupling in the (δ, θ), (δ, β), (δ, γ1), and (δ, γ2) frequency pairs. These findings support the presence of an RC organization simultaneously with dominant frequency interactions within a single functional graph. Our results demonstrate a hyperactivation of intrinsic RC networks in mTBI subjects compared to controls, which can be seen as a plausible compensatory mechanism for alternative frequency-dependent routes of information flow in mTBI subjects.
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Comparative Study
Comparison of the induction of c-fos-eGFP and Fos protein in the rat spinal cord and hypothalamus resulting from subcutaneous capsaicin or formalin injection.
We evaluated whether a c-fos-enhanced green fluorescent protein (eGFP) transgenic rat line, which expresses the c-fos and eGFP fusion gene, can be useful for the study of nociceptive pathways and processing. Capsaicin solution (15%) or formalin (5%) was subcutaneously injected bilaterally into the hind paws (100μL per each paw) of adult male c-fos-eGFP transgenic or wild-type rats. Control rats were injected with ethanol or physiological saline respectively. ⋯ Following capsaicin or formalin treatment, eGFP was maximally expressed at 6h in the spinal cord and 3h in the PVN and SON, whereas, Fos-LI was maximally expressed at 1.5h in all the regions we analyzed. Induction of eGFP in the OXT neurons was observed after capsaicin or formalin treatment, while Fos-LI in the OXT neurons was observed only after formalin treatment. These results demonstrate that the peak induction of c-fos-eGFP following exposure to acute nociceptive stimuli was delayed by around 1.5-4.5h, but more sensitive than endogenous Fos, suggesting that the c-fos-eGFP rat line can be useful for the study of nociceptive pathways and processing.
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The thalamus is one of the most commonly affected brain regions in preterm infants, particularly in infants with white matter lesions (WML). The aim of this paper is to explore the development and alterations of the functional thalamocortical connectivity in preterm infants with and without punctate white matter lesions (PWMLs) during the period before term equivalent age (TEA). In this study, twenty-two normal preterm infants (NP), twenty-two preterm infants with PWMLs and thirty-one full-term control infants (FT) were enrolled. ⋯ Both preterm groups exhibited prominent development in thalamo-SA and thalamo-SM connectivity during this period. Compared with NP infants, PWML infants demonstrated increased connectivity in the parietal area in thalamo-SA connectivity but no significant differences in thalamo-SM connectivity. Our results reveal that compared with NP infants, PWML infants exhibit slightly altered thalamo-SA connectivity, and this alteration is deduced to be functional compensations for inefficient thalamocortical processing due to PWMLs.
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Goal-oriented arm movements are characterized by a balance between speed and accuracy. The relation between speed and accuracy has been formalized by Fitts' law and predicts a linear increase in movement duration with task constraints. Up to now this relation has been investigated on a short-time scale only, that is during a single experimental session, although chronobiological studies report that the motor system is shaped by circadian rhythms. ⋯ While Fitts' law was held for the whole sessions of the day, the slope of the relation between movement duration and task difficulty expressed a clear modulation, with the lowest values in the afternoon. This variation of the speed-accuracy trade-off in executed and mental movements suggests that, beyond execution parameters, motor planning mechanisms are modulated during the day. Daily update of forward models is discussed as a potential mechanism.