Neuroscience
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Transactive response DNA-binding protein 43 (TDP-43) is a predominantly nuclear, ubiquitously expressed RNA and DNA-binding protein. It recognizes and binds to UG repeats and is involved in pre-mRNA splicing, mRNA stability and microRNA metabolism. TDP-43 is essential in early embryonic development but accumulates in cytoplasmic aggregates in amyotrophic lateral sclerosis (ALS) and tau-negative frontotemporal lobar degeneration (FTLD). ⋯ We show that Ran-binding protein 1 (RanBP1), DNA methyltransferase 3 alpha (Dnmt3a) and chromogranin B (CgB) are downregulated upon TDP-43 knockdown. Subsequently, transportin 1 level is increased as a result of RanBP1 depletion. Improper regulation of these proteins and the subsequent disruption of cellular processes may play a role in the pathogenesis of the TDP-43 proteinopathies ALS and FTLD.
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To measure changes in amplitudes of vestibular evoked myogenic potentials (VEMPs) elicited from neck, upper and lower limb muscles during a quiet standing task with increased postural threat achieved by manipulating surface height. ⋯ Postural threat significantly increased vestibulospinal reflex (VSR) gains. Results demonstrate that VEMPs can be used to test different VSR pathways simultaneously during stance. Since fear and anxiety are prevalent with vestibular disorders, they should be considered as potential contributing factors for clinical vestibular outcome measures.
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Modulation of actin and microtubule (MT) dynamics in neurons is implicated in guidance cue-dependent axon outgrowth, branching and pathfinding. Although the role of MTs in axon guidance has been well known, how extracellular guidance signals engage MT behavior in axon branching remains unclear. Previously, we have shown that TUBB3, the most dynamic β-tubulin isoform in neurons, directly binds to deleted in colorectal cancer (DCC) to regulate MT dynamics in Netrin-1-mediated axon guidance. ⋯ Knockdown of DSCAM only, DCC only or both was sufficient to block Netrin-1-induced axon branching of E15 mouse cortical neurons. Knocking down TUBB3 inhibited Netrin-1 induced axon branching as well. These results suggest that DSCAM collaborates with DCC to regulate MT dynamics via direct binding to dynamic TUBB3 in Netrin-1-induced axon branching.
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We previously showed that isovaline is a peripheral analgesic which acts in vivo and in brain slices as an atypical metabotropic GABA(B) agonist. Peripheral inhibitory group II and III metabotropic glutamate receptors (mGluRs) belong to the same family C as GABA(B) receptors; therefore, we hypothesized that isovaline's analgesic effects could include their activation. We examined the effects of R-isovaline on mechanical allodynia produced by prostaglandin E2 in the mouse paw. ⋯ Hence, there was no apparent crosstalk between group II mGluRs and GABA(B) receptors. Previous studies have demonstrated that peripheral GABA(B) receptor activation by isovaline produces antiallodynia. In addition, the present results indicate that activation of peripheral group II mGluRs by R-isovaline produces antiallodynia.
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Motor commands issued by the CNS are based upon memories of past experiences with similar objects, the current state of the hand and arm postures, and sensory input. Thus widespread somatosensory information is available to form precise representations of hand shape on which to base motor commands to match a desired posture or movement. The aim of this study was to examine the extent to which somatosensory information reflecting external influences on independent finger movement is incorporated into the perception of hand shape driving the motor command. ⋯ The hypothesis was that the same synergies (patterns of activation across muscles) would be used to complete the task but would be rescaled with respect to condition. The results demonstrated that rescaling the patterns of multi-muscle activity from the unconstrained condition could not equivalently represent those from the constrained conditions. Thus it appears that external restriction of independent finger movement was signaled by somatosensory feedback and incorporated into the desired state driving the motor command resulting in selective activation of groups of muscles.