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Highlights • White matter stroke is a prominent stroke subtype. • White matter stroke is a leading cause of dementia (vascular dementia) and commonly co-occurs with Alzheimer’s disease. • Unlike multiple sclerosis, there is no cellular repair process in white matter stroke. • Several animal models of white matter exist, each with strengths and limitations. • Recent studies have defined specific molecular systems involved in white matter stroke outcomes. Abstract White matter stroke (WMS) is a debilitating disorder, which is characterized by the formation of ischemic lesions along subcortical white matter tracts of the central nervous system. Initial infarction during the early stages of the disease is often asymptomatic and is thus considered a form of silent stroke. However, over time lesions accumulate, resulting in severe cognitive and motor decline of which there are no known therapies. Functional imaging and post mortem analysis of patients demonstrates a loss of oligodendrocytes and the subsequent damage of myelin as a primary hallmark of WMS lesions. Though the adult mammalian brain maintains the capacity to regenerate adult oligodendrocytes, this process is blocked in the infarcted white matter thereby preventing remyelination. Recent evidence suggests that activation of neural circuits via motor training or direct stimulation drives oligodendrogenesis and de novo myelin synthesis, opening a potential avenue for therapy in WMS. [ABSTRACT FROM AUTHOR]

Highlights • Reaction time was lengthened as the task became more complex. • APA profiles were scaled to the complexity of the task. • APAs are preplanned to maintain balance while successfully completing a complex task. Abstract The central nervous system preplans postural responses to successfully perform complex multi-joint movements. These responses have been termed anticipatory postural adjustments (APAs), and they constitute a general type of response to stabilize posture prior to movement initiation. APA sequences are elicited with shorter latency when a startling acoustic stimulus is applied, demonstrating their preplanned nature. Increasing task complexity using a simple reaction time (RT) paradigm has been shown to delay limb movement RT as a result of additional planning or sequencing requirements; however, the effect of task complexity on APA dynamics is unclear. The purpose of the present study was to investigate if task complexity modulates APA onset in a manner analogous to that observed in the primary effector. 13 participants completed 150 trials of simple (1-target) and complex (2- or 3-target) arm movements while standing on a force plate. Results indicated participants had significantly faster arm movement RTs in the simple versus the most complex condition. Similar to the primary effector, APA RTs were longer in the most complex (3-target) movement compared to both the 1-target and 2-target movements. Furthermore, APA excursion velocities were scaled to the complexity of the upcoming movement: the rate of APAs increased from simplest to most complex movements. These findings clearly demonstrate APAs are sensitive to task complexity, further elucidating their preplanned role in stabilizing posture which enables the successful completion of intended movements. [ABSTRACT FROM AUTHOR]

The myelin sheath that insulates some axons in the central nervous system allows for faster signal conduction. Previously, axons were thought to be either unmyelinated or fully myelinated. Recent experimental work has discovered a new pattern of myelination (intermittent myelination) along axons in the mouse brain, in which long unmyelinated axon segments are followed by myelinated segments of comparable length. We use a computational model to explore how myelin distribution (in particular intermittent myelination) affects conduction velocity. We find that although fully myelinated axons minimize conduction velocity, varying the spatial distribution of a fixed amount of myelin along a partially myelinated axon leads to considerable variation in the conduction velocity for action potentials. Whether sodium ion channel number or sodium ion channel density is held constant as the area of the unmyelinated segments increases has a strong influence on the optimal pattern of myelin and the conduction velocity. [ABSTRACT FROM AUTHOR]

Sprint motor performance, such as in short-distance running or cycling, gradually decreases after reaching a maximum speed or cadence. This may be attributed to the central nervous system. Brain stimulation studies have recently revealed the plastic nature of the human brain and spinal cord, but it is unclear how direct current stimulation (DCS) affects sprint motor performance. To address this issue, we investigated DCS’s effect on healthy volunteers’ sprint cycling performance. DCS was applied to the lumbar spinal cord (3 mA) or the leg area of the motor cortex (2 mA) for 15 min with 3 different polarities: anodal, cathodal, and sham. After DCS, the subjects performed maximal-effort sprint cycling for 30 s under a constant load. Pooled mean power during the 30 s was significantly greater after cathodal transcutaneous spinal DCS to the lumbar spinal cord (tsDCS) than anodal or sham tsDCS. The improvement with cathodal stimulation was notable both 0–5 and 20–25 s after the performance onset. There were no significant inter-conditional differences in peak power. Pooled mean power was significantly greater after anodal transcranial DCS to the motor cortex (tDCS) than after cathodal tDCS, although mean powers of anodal and sham tDCS were not significantly different. The increase in mean power after cathodal tsDCS could result from a reduction in central fatigue. This stimulus method might improve sprint performance. [ABSTRACT FROM AUTHOR]

Autophagy widely occurs after intracerebral hemorrhage (ICH). In our previous study, we demonstrated that thrombin, a serine protease produced after hematoma, contributes to ICH-induced autophagy. However, whether thrombin plays a neuronal and/or astrocytic role in autophagy induction is largely unknown. Here, we examined the autophagic role of thrombin on neurons and glia cells, respectively. In vivo, we found that intracaudate injection of thrombin specifically elevated the astrocytic expression of beclin-1 and LC3, two autophagic markers, and promoted the formation of autophagic vacuoles within astrocytes rather than neurons in the ipsilateral basal ganglia. Consistent with this, thrombin enhanced the LC3-II level and increased the number of MDC-labeled autophagic vacuoles in cultured astrocytes. These results indicated that thrombin preferentially activated astrocytic autophagy after ICH, and therefore provided novel insights into the pathophysiological mechanisms and therapeutic targets for hemorrhage stroke and brain trauma. [ABSTRACT FROM AUTHOR]

The DA transporter (DAT), a phosphoprotein, controls extracellular dopamine (DA) levels in the central nervous system through transport or reverse transport (efflux). Multiple lines of evidence support the claim that PKC significantly contributes to amphetamine-induced DA efflux. Other signaling pathways, involving CaMKII and ERK, have also been shown to regulate DAT mediated efflux. Here we assessed the contribution of putative PKC residues (S4, S7, S13) in the N-terminal of the DAT to amphetamine-induced DA efflux by transfecting DATs containing different serine to alanine (S-A) point mutations into DA pre-loaded HEK-293 cells and incubating these cells in amphetamine (2 μM). The effects of a S-A mutation at the non-PKC residue S12 and a threonine to alanine (T-A) mutation at the ERK T53 residue were also assessed for comparison. WT-DATs were used as controls. In an initial experiment, we confirmed that inhibiting PKC with Go6976 (130 nM) significantly reduced amphetamine-induced DA efflux. In subsequent experiments, cells transfected with the S4A, S12A, S13A, T53A and S4,7,13A mutants showed a reduction in amphetamine-induced DA efflux similar to that observed with Go6976. Interestingly, cells transfected with the S7A mutant, identified by some as a PKC-PKA residue, showed unperturbed WT-DAT levels of amphetamine-induced DA efflux. These results indicate that phosphorylation by PKC of select residues in the DAT N-terminal can regulate amphetamine-induced efflux. PKC can act either independently or in concert with other kinases such as ERK to produce this effect. [ABSTRACT FROM AUTHOR]

Harmane is an active component of clonidine displacing substance and a candidate endogenous ligand for imidazoline binding sites. The neurochemistry of tritiated harmane was investigated in the present study examining its uptake and release properties in the rat brain central nervous system (CNS) in vitro . At physiological temperature, [ 3 H]harmane was shown to be taken up in rat brain cortex. Further investigations demonstrated that treatment with monoamine uptake blockers (citalopram, nomifensine and nisoxetine) did not alter [ 3 H]harmane uptake implicating that the route of [ 3 H]harmane transport was distinct from the monoamine uptake systems. Furthermore, imidazoline ligands (rilmenidine, efaroxan, 2-BFI and idazoxan) showed no prominent effect on [ 3 H]harmane uptake suggesting the lack of involvement of imidazoline binding sites. Subsequent analyses showed that disruption of the Na + gradient using ouabain or choline chloride did not block [ 3 H]harmane uptake suggesting a Na + -independent transport mechanism. Moreover, higher temperatures (50 °C) failed to impede [ 3 H]harmane uptake implying a non-physiological transporter. The failure of potassium to evoke the release of preloaded [ 3 H]harmane from rat brain cortex indicates that the properties of this putative endogenous ligand for imidazoline binding sites do not resemble that of a conventional neurotransmitter. [ABSTRACT FROM AUTHOR]

Highlights: [•] The interplay of death reminders and cultural coping is tested on a neural level. [•] Death priming preceding the viewing of culture content was associated with specific brain activation patterns. [•] Neither neutral nor meaning-threat priming preceding cultural content were associated with such activation. [•] This supports the idea that notions of mortality evoke cultural worldview defense. [ABSTRACT FROM AUTHOR]

Abstract: Transcranial magnetic stimulation is a non-invasive tool in clinical diagnostics and therapy for physiological and psychological diseases and has an increased application in experimental neurophysiology. Despite this, the mechanisms of magnetic stimulation of the central nervous system remain still unclear. We applied sinus-shaped high frequency magnetic fields in different stimulation patterns and repeated treatments to cell cultures derived from frontal cortex of murine embryos (BALB/cOlaHsd mice) to elucidate the effects of repetitive magnetic stimulation on the gene expression of in vitro cultured neural cells. Gene expression profiling was performed by using qRT-PCR array and single qRT-PCR analyses. Our methodological approach using microelectrode arrays data recording and analysis minimizes variations in transcriptome analysis arising from cell differentiation status and tissue complexity. With 10 significant changes in gene expression out of 171 genes using Alzheimer disease and neurodegeneration related qRT-PCR arrays we demonstrate significant impact of repetitive magnetic stimulation on the mRNA transcript of neural cell cultures. Sixteen candidate genes were analyzed using single qRT-PCR in a replicated statistical design, which provided more precise estimates of differences in expression profiles. We discussed the utility of the experimental methods used for cell culture selection and the changes in gene expression considering physiological aspects. [Copyright &y& Elsevier]

Abstract: Little is known about the somatotopic location of the corticospinal tract (CST) in the centrum semiovale (CS). We investigated the somatotopic location of the CST in the CS in the human brain using diffusion tensor tractography (DTT). Fifty-two healthy volunteers were recruited for this study. Diffusion tensor images (DTIs) were obtained at 1.5T, and CSTs for the hand and leg were obtained using FMRIB software. Normalized DTT images were reconstructed using the Montreal Neurological Institute echo-planar imaging template supplied with the SPM. Individual DTI data were calculated as number of pixels in the CS. In the mediolateral direction, average distances of the highest probabilistic locations for hand and leg somatotopies were 25.57mm and 21.72mm from the midline between the right and left hemispheres, respectively. For the anteroposterior direction, the average distance of the highest probabilistic locations for hand and leg somatotopies were 0.4mm and 5.2mm behind the horizontal line between the medial end of the central sulcus and midline, respectively. In conclusion, hand somatotopy of the CST was found to be located at about 26mm lateral to the midline almost along the horizon line between the medial end of central sulcus and midline, and leg somatotopy of the CST was found to be located medioposteriorly to the hand somatotopy of the CST. [Copyright &y& Elsevier]

Abstract: Transgenic rats expressing a mutated form of the human Cu/Zn superoxide dismutase (hSOD1G93A) develop an amyotrophic lateral sclerosis (ALS)-like phenotype, including motor neurone degeneration and reactive gliosis in the spinal cord. This study aimed at examining the presence of endogenous neural progenitors in the lumbar spinal cord of these rats at the end-stage of the disease. Immunohistochemical data clearly demonstrated the induced expression of the stem cell factor reported as a chemoattractant and survival factor for neural stem cells as well as nestin (neuro-epithelial stem cell intermediate filament) in the spinal cord sections. While the stem cell factor immunolabelling appeared diffuse throughout the gray matter, nestin labelling was restricted to clusters within the ventral horn. Interestingly, as paralysis regularly develops asymmetrically, induction of nestin was only detected on the ipsilateral side of the predominant symptoms. Finally, immunohistochemical detection of the stem cell factor receptor (c-Kit) revealed its specific induction which coincided with nestin immunolabelling. Together, these results are indicative of endogenous recruitment of neural progenitors within lesioned tissues and could support the development of treatments involving endogenous or exogenous stem cells. [Copyright &y& Elsevier]