Neuroscience
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Intrinsic connectivity networks (ICNs) are composed of spatial components and time courses. The spatial components of ICNs were discovered with moderate-to-high reliability. So far as we know, few studies focused on the reliability of the temporal patterns for ICNs based their individual time courses. ⋯ Specially, our results supported that mEPI could be a useful method with high reliability and reproducibility. In addition, these temporal patterns were with physiological meanings, and certain temporal patterns were correlated to the node strength of the corresponding ICN. Overall, network-wise temporal patterns of ICNs were reliable and informative and could be complementary to spatial patterns of ICNs for further study.
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Neurogenesis continues to occur in restricted regions of the brain throughout adulthood and can be modulated by dietary factors. Liquid or "soft" diets are commonly used for the administration of drugs in experimental models of disease, making it critical to determine whether dietary composition itself can affect neurogenesis. In this study Sprague-Dawley rats were fed either a liquid or a solid diet of identical composition from weaning until young adulthood. ⋯ The method of feeding did not alter the basal function of the hypothalamic-pituitary-adrenal (HPA) axis in these animals, as no changes in circulating levels of corticosterone (CORT) were detected between liquid and solid diet-fed groups. There was also a significant reduction in cellular proliferation in the hypothalamus of liquid diet-fed rats, a brain region known to be involved in feeding-related behaviors. These findings indicate that liquid diets themselves can directly impact rates of cellular proliferation, but this does not seem to impact levels of overall neurogenesis in the adult brain.
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Randomized Controlled Trial
Parkinson's disease patients show impaired corrective grasp control and eye-hand coupling when reaching to grasp virtual objects.
The effect of Parkinson's disease (PD) on hand-eye coordination and corrective response control during reach-to-grasp tasks remains unclear. Moderately impaired PD patients (n=9) and age-matched controls (n=12) reached to and grasped a virtual rectangular object, with haptic feedback provided to the thumb and index fingertip by two 3-degree of freedom manipulanda. The object rotated unexpectedly on a minority of trials, requiring subjects to adjust their grasp aperture. ⋯ Strikingly, PD patients tracked their hands with their gaze, and their movements became destabilized when having to make online corrective responses to object perturbations exhibiting pauses and changes in movement direction. These impairments largely remained even when tested in the ON state, despite significant improvement on the Unified Parkinson's Disease Rating Scale. Our findings suggest that basal ganglia-cortical loops are essential for mediating eye-hand coordination and adaptive online responses for reach-to-grasp movements, and that restoration of tonic levels of dopamine may not be adequate to remediate this coordinative nature of basal ganglia-modulated function.
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Nerve growth factor (NGF) augments the excitability of isolated rat sensory neurons through activation of the p75 neurotrophin receptor (p75(NTR)) and its downstream sphingomyelin signaling cascade, wherein neutral sphingomyelinase(s) (nSMase), ceramide, and the atypical protein-kinase C (aPKC), protein-kinase M zeta (PKMζ), are key mediators. Here we examined these same receptor-pathways in vivo for their role in mechanical hyperalgesia from exogenous NGF. Mechanical sensitivity was tested by the number of paw withdrawals in response to 10 stimuli (PWF=n/10) by a 4-g von Frey hair (VFH, testing "allodynia") and by 10 and 15g VFHs (testing "hyperalgesia"). ⋯ Hyperalgesia from both NGF and mPro-NGF was prevented by paw pre-injection with blocking antibodies to rat p75(NTR) receptor. Finally, intraplantar (1day before NGF) injection of mPSI, the myristolated pseudosubstrate inhibitor of PKCζ/PKMζ, decreased the hyperalgesia resulting from NGF or C2-ceramide, although scrambled mPSI was ineffective. The findings indicate that mechano-hypersensitivity from peripheral NGF involves the sphingomyelin signaling cascade activated via p75(NTR), and that a peripheral aPKC is essential for this sensitization.
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Microglia have been implicated in disease progression for several age-related brain disorders. However, while microglia's contribution to the progression of these disorders is accepted, the effect of aging on their endogenous cellular characteristics has received limited attention. In fact, a comprehensive study of how the structure and function of microglia changes as a function of developmental age has yet to be performed. ⋯ Interestingly, 13-15month-old microglia exhibited similar activation profiles to Neo microglia, whereas microglia from younger adults and embryos were activated less by ATP. Our data also identify age-dependent differences in purinergic receptor subtype expression that contribute to the regulation of neuronal survival. Combined, our data demonstrate that microglial activation and purinergic receptor profiles vary non-linearly with developmental age, a potentially important finding for studies examining the role of microglia in neurodegenerative disorders.