Neuroscience
-
Neuroinflammation is a key component of the pathophysiology of neurodegenerative diseases. The link between nicotine intake and positive outcome has been established, suggesting a role played by nicotinic receptors (nAChRs), especially α7nAChRs. The objective of this study was to evaluate the potential dose effects of PHA 543613 on neuron survival and striatal microglial activation in a rat model of brain excitotoxicity. ⋯ We demonstrated that [3H]DPA-714 provides a better signal-to-noise ratio than [3H]PK-11195. Furthermore, we showed that repeated PHA 543613 administration at a dose of 12mg/kg to QA-lesioned rats significantly protected neurons and reduced the intensity of microglial activation. This study reinforces the hypothesis that α7nAChR agonists can provide beneficial effects in the treatment of neurodegenerative diseases through potential modulation of microglial activation.
-
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.
-
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.
-
Time perception in the millisecond and second ranges is thought to be processed by different neural mechanisms. However, whether there is a sharp boundary between these ranges and whether they are implemented in the same, overlapped or separate brain areas is still not certain. To probe the role of the right dorsolateral prefrontal cortex (dlPFC), the right supplementary motor area (SMA), and the cerebellum on time perception, we temporarily altered their activity on healthy volunteers on separate sessions using transcranial magnetic stimulation with the continuous Theta Burst Stimulation (cTBS) protocol. ⋯ We found that after cTBS in all of the studied regions, the Relative Threshold, but not the Constant Error, was affected and only when hundreds of milliseconds intervals were being categorized. Categorization of thousands of milliseconds intervals and of pitch was not affected. These results suggest that the fronto-cerebellar circuit is particularly involved in the estimation of intervals in the hundreds of milliseconds range.
-
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.