Neuroscience
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The protective effects of taurine against closed head injury (CHI) have been reported. This study was designed to investigate whether taurine reduced white matter damage and hippocampal neuronal death through suppressing calpain activation after CHI in rats. ⋯ Moreover, it suppressed the over-activation of calpain, enhanced the levels of calpastatin, and reduced the degradation of neurofilament heavy protein, myelin basic protein and αII-spectrin in traumatic tissue 24 h after CHI. These data confirm the protective effects of taurine against gray and white matter damage due to CHI, and suggest that down-regulating calpain activation could be one of the protective mechanisms of taurine against CHI.
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Simvastatin is an HMG-CoA reductase inhibitor commonly used in the clinic to treat hypercholesterolemia. In addition, simvastatin has been shown to cross the blood-brain barrier and pleiotropic effects of simvastatin have been reported including anti-inflammatory properties, enhancement of neurite outgrowth, and memory enhancement properties. However, little has been reported on the effects of simvastatin on basal synaptic transmission and neuronal excitability. ⋯ We have also observed that acute application of simvastatin increased the amplitude of the compound action potential in the CA1 region. Notably, using LY294002, we have demonstrated that this effect was PI3K dependent and was occluded if the animals had previously received a diet supplemented with simvastatin. We have finally shown that the simvastatin-mediated increase of the compound action potential amplitude was also present in hippocampal slices from aged mice.
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Synaptic plasticity is the capacity of a preexisting connection between two neurons to change in strength as a function of neural activity. Because synaptic plasticity is the major candidate mechanism for learning and memory, the elucidation of its constituting mechanisms is of crucial importance in many aspects of normal and pathological brain function. In particular, a prominent aspect that remains debated is how the plasticity mechanisms, that encompass a broad spectrum of temporal and spatial scales, come to play together in a concerted fashion. Here we review and discuss evidence that pinpoints to a possible non-neuronal, glial candidate for such orchestration: the regulation of synaptic plasticity by astrocytes.
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Comparative Study
Modulation of forelimb and hindlimb muscle activity during quadrupedal tied-belt and split-belt locomotion in intact cats.
The modulation of the neural output to forelimb and hindlimb muscles when the left and right sides step at different speeds from one another in quadrupeds was assessed by obtaining electromyography (EMG) in seven intact adult cats during split-belt locomotion. To determine if changes in EMG during split-belt locomotion were modulated according to the speed of the belt the limb was stepping on, values were compared to those obtained during tied-belt locomotion (equal left-right speeds) at matched speeds. Cats were chronically implanted for EMG, which was obtained from six muscles: biceps brachii, triceps brachii, flexor carpi ulnaris, sartorius, vastus lateralis and medial gastrocnemius. ⋯ During split-belt locomotion, there was a clear differential modulation of the EMG patterns between flexors and extensors and between the slow and fast sides. Changes in the EMG pattern of some muscles could be explained by the speed of the belt the limb was stepping on, while in other muscles there were clear dissociations from tied-belt values at matched speeds. Therefore, results show that EMG patterns during split-belt locomotion are modulated to meet task requirements partly via signals related to the stepping speed of the homonymous limb and from the other limbs.
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Parkinson's disease (PD) is a progressive neurological disorder and current therapies help alleviate symptoms, but are not disease modifying. In the flavonoid class of compounds, 7,8-dihydroxyflavone (7,8-DHF) has been reported to elicit tyrosine kinase receptor B (TrkB) dimerization and autophosphorylation that further stimulates signaling cascades to promote cell survival/growth, differentiation, and plasticity. In this study we investigated if 7,8-DHF could prevent further loss of dopaminergic cells and terminals if introduced at the midpoint (i.e. intervention) of our progressive mouse model of PD. ⋯ In addition, motor deficits seen in the 2- and 4-week MPTP-treated animals were restored following administration of 7,8-DHF. We are reporting here for the first time that intervention with 7,8-DHF blocks further loss of dopaminergic terminals and restores motor deficits in our progressive MPTP mouse model. Our data suggest that 7,8-DHF has the potential to be a translational therapy in PD.