194 research outputs found

    Structural And Chemical Organization Of The Rat Interpeduncular Nucleus

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    The structural and chemical organization of the rat interpeduncular nucleus (IPN) was examined employing wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) and immunohistochemistry at the light and electron microscope level. The topographical and ultrastructural arrangements of habenular efferents innervating the IPN were studied using stereotaxic placements of WGA-HRP. The medial habenula provided a prominent afferent input to the many IPN subnuclei, with the lateral and rostral subnuclei receiving a predominantly ipsilateral input, and the intermediate, central and dorsomedial subnuclei receiving a symmetrical projection. Habenular terminals formed distinct axodendritic synapses in the rostral, lateral, intermediate and central subnuclei.;Projections of the fasciculus retroflexus (FR) were stained immunohistochemically for choline acetyltransferase (ChAT) or substance P (SP). These inputs were topographically organized among the IPN subnuclei, such that ChAT-positive axons innervated the rostral, intermediate and central subnuclei, and SP-positive inputs terminated in the lateral, dorsomedial and rostral subnuclei. Characteristic axodendritic synapses of the intermediate, central and rostral subnuclei were composed of ChAT-positive terminals, and those in the lateral, rostral and dorsomedial subnuclei were composed of SP-positive terminals.;A prominent population of neurons and an extensive plexus of axons and terminals stained immunohistochemically for glutamic acid decarboxylase (GAD) were present in the rostral, lateral, central and intermediate subnuclei. Axodendritic and axosomatic synapses possessing GAD immunoreactivity pre - and/or postsynaptically were evident in these subnuclei. GAD-immunoreactive dendrites in the intermediate, central and rostral subnuclei also received ChAT-positive terminals, and those in the lateral subnucleus received SF-positive terminals. SP-positive dendrites in the rostral subnucleus were also in receipt of ChAT-positive terminals.;The IPN is considered to be an important link between the septohabenular circuit of the limbic forebrain and several raphe and tegmental centres of the hindbrain. Neurons of the IPN are in receipt of descending habenular projections which provide putative excitatory inputs, as well as intrinsic, putative inhibitory inputs. The integration of habenular inputs with those arising from intrinsic sources may play an important role in the direct and transsynaptic modulation of projection neurons of the IPN which provide afferent inputs to the raphe and tegmental centres of the hindbrain

    Byod Approach To Blended Learning In Developing Nations

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    Businesses are adopting Bring Your Own Device (BYOD) policies in their organisations to allow employees to bring personal mobile devices to work. This approach can be adopted in education to address the educational divide between developing and developed nations. A BYOD approach to education could entail the use of cheap tablets to deliver educational content but would require an appropriate blended learning approach for learning to be effective. Consequently, the objective of this paper is to investigate the effectiveness of different blended learning approaches with tablets as an instructional medium. A conceptual model for blended learning was constructed from learning theories in the literature. Subsequently, experiments were conducted to investigate the impact of media richness, collaborative work and performance feedback on learner performance, engagement and satisfaction. The results have implications on educators who plan to design tablet-based blended learning arrangements

    BACE1 activity impairs neuronal glucose oxidation:rescue by beta-hydroxybutyrate and lipoic acid

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    Glucose hypometabolism and impaired mitochondrial function in neurons have been suggested to play early and perhaps causative roles in Alzheimer's disease (AD) pathogenesis. Activity of the aspartic acid protease, beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1), responsible for beta amyloid peptide generation, has recently been demonstrated to modify glucose metabolism. We therefore examined, using a human neuroblastoma (SH-SY5Y) cell line, whether increased BACE1 activity is responsible for a reduction in cellular glucose metabolism. Overexpression of active BACE1, but not a protease-dead mutant BACE1, protein in SH-SY5Y cells reduced glucose oxidation and the basal oxygen consumption rate, which was associated with a compensatory increase in glycolysis. Increased BACE1 activity had no effect on the mitochondrial electron transfer process but was found to diminish substrate delivery to the mitochondria by inhibition of key mitochondrial decarboxylation reaction enzymes. This BACE1 activity-dependent deficit in glucose oxidation was alleviated by the presence of beta hydroxybutyrate or α-lipoic acid. Consequently our data indicate that raised cellular BACE1 activity drives reduced glucose oxidation in a human neuronal cell line through impairments in the activity of specific tricarboxylic acid cycle enzymes. Because this bioenergetic deficit is recoverable by neutraceutical compounds we suggest that such agents, perhaps in conjunction with BACE1 inhibitors, may be an effective therapeutic strategy in the early-stage management or treatment of AD

    Combined delivery of Nogo-A antibody, neurotrophin-3 and the NMDA-NR2d subunit establishes a functional ‘detour’ in the hemisected spinal cord

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    To encourage re-establishment of functional innervation of ipsilateral lumbar motoneurons by descending fibers after an intervening lateral thoracic (T10) hemisection (Hx), we treated adult rats with the following agents: (i) anti-Nogo-A antibodies to neutralize the growth-inhibitor Nogo-A; (ii) neurotrophin-3 (NT-3) via engineered fibroblasts to promote neuron survival and plasticity; and (iii) the NMDA-receptor 2d (NR2d) subunit via an HSV-1 amplicon vector to elevate NMDA receptor function by reversing the Mg2+ block, thereby enhancing synaptic plasticity and promoting the effects of NT-3. Synaptic responses evoked by stimulation of the ventrolateral funiculus ipsilateral and rostral to the Hx were recorded intracellularly from ipsilateral lumbar motoneurons. In uninjured adult rats short-latency (1.7-ms) monosynaptic responses were observed. After Hx these monosynaptic responses were abolished. In the Nogo-Ab + NT-3 + NR2d group, long-latency (approximately 10 ms), probably polysynaptic, responses were recorded and these were not abolished by re-transection of the spinal cord through the Hx area. This suggests that these novel responses resulted from new connections established around the Hx. Anterograde anatomical tracing from the cervical grey matter ipsilateral to the Hx revealed increased numbers of axons re-crossing the midline below the lesion in the Nogo-Ab + NT-3 + NR2d group. The combined treatment resulted in slightly better motor function in the absence of adverse effects (e.g. pain). Together, these results suggest that the combination treatment with Nogo-Ab + NT-3 + NR2d can produce a functional ‘detour’ around the lesion in a laterally hemisected spinal cord. This novel combination treatment may help to improve function of the damaged spinal cord

    Bioprocessing strategies to enhance the challenging isolation of neuro-regenerative cells from olfactory mucosa

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    Olfactory ensheathing cells (OECs) are a promising potential cell therapy to aid regeneration. However, there are significant challenges in isolating and characterizing them. In the current study, we have explored methods to enhance the recovery of cells expressing OEC marker p75NTR from rat mucosa. With the addition of a 24-hour differential adhesion step, the expression of p75NTR was significantly increased to 73 ± 5% and 46 ± 18% on PDL and laminin matrices respectively. Additionally, the introduction of neurotrophic factor NT-3 and the decrease in serum concentration to 2% FBS resulted in enrichment of OECs, with p75NTR at nearly 100% (100 ± 0% and 98 ± 2% on PDL and laminin respectively), and candidate fibroblast marker Thy1.1 decreased to zero. Culturing OECs at physiologically relevant oxygen tension (2–8%) had a negative impact on p75NTR expression and overall cell survival. Regarding cell potency, co-culture of OECs with NG108-15 neurons resulted in more neuronal growth and potential migration at atmospheric oxygen. Moreover, OECs behaved similarly to a Schwann cell line positive control. In conclusion, this work identified key bioprocessing fundamentals that will underpin future development of OEC-based cell therapies for potential use in spinal cord injury repair. However, there is still much work to do to create optimized isolation methods

    Cellular therapies for treating pain associated with spinal cord injury

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    Spinal cord injury leads to immense disability and loss of quality of life in human with no satisfactory clinical cure. Cell-based or cell-related therapies have emerged as promising therapeutic potentials both in regeneration of spinal cord and mitigation of neuropathic pain due to spinal cord injury. This article reviews the various options and their latest developments with an update on their therapeutic potentials and clinical trialing

    Astrocyte scar formation aids central nervous system axon regeneration

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    Transected axons fail to regrow in the mature central nervous system. Astrocytic scars are widely regarded as causal in this failure. Here, using three genetically targeted loss-of-function manipulations in adult mice, we show that preventing astrocyte scar formation, attenuating scar-forming astrocytes, or ablating chronic astrocytic scars all failed to result in spontaneous regrowth of transected corticospinal, sensory or serotonergic axons through severe spinal cord injury (SCI) lesions. By contrast, sustained local delivery via hydrogel depots of required axon-specific growth factors not present in SCI lesions, plus growth-activating priming injuries, stimulated robust, laminin-dependent sensory axon regrowth past scar-forming astrocytes and inhibitory molecules in SCI lesions. Preventing astrocytic scar formation significantly reduced this stimulated axon regrowth. RNA sequencing revealed that astrocytes and non-astrocyte cells in SCI lesions express multiple axon-growth-supporting molecules. Our findings show that contrary to the prevailing dogma, astrocyte scar formation aids rather than prevents central nervous system axon regeneration

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