Brain and nerve = Shinkei kenkyū no shinpo
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A reliable objective marker of upper motor neuron (UMN) involvement is critical for early diagnosis and monitoring disease course in patients with amyotrophic lateral sclerosis (ALS). Lower motor neuron (LMN) involvement can be identified by electromyography, whereas UMN dysfunction has been currently distinguished solely by neurological examination. In the search for diagnostic tests to evaluate UMN involvement in ALS, numerous reports on new markers using neurophysiological and imaging techniques are accumulating. ⋯ Diffusion tensor tractography allows for visualization and evaluation of corticospinal and corticobulbar tract dysfunction individually in patients with ALS. Although many of these new approaches do not yet reach clinical significance, they have been extensively explored in objective evaluation of upper motor function in patients with ALS. Further investigation is needed to determine and to compare the utility of various neurophysiological and neuroimaging markers.
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Neuropathic pain resulting from nerve injury or from diseases such as diabetes, HIV AIDS or cancer, that damage the peripheral nerves, can be agonizing, persistent over long periods, and, unfortunately, is often resistant to known pain-killers. The P2X receptors, of which seven subtypes (P2X1-P2X7) have been cloned, are a family of ligand-gated cation channels activated by extracellular ATP and have important roles in regulating neuronal and glial functions in the nervous system. Recent advances in our understanding of the mechanisms underlying neuropathic pain have been made by defining important roles of P2X4 receptors and spinal microglia in the pathogenesis of neuropathic pain. ⋯ Furthermore, P2X4 receptors that which are upregulated in activated microglia, have been found to be essential molecular mediators. The activation of P2X4 receptors releases brain-derived neurotrophic factor from microglia; this mediates the signaling from microglia to neurons, which in turn leads to pain hypersensitivity. We expect that understanding the key roles of these molecules in spinal microglia may lead to new strategies for the management of neuropathic pain.
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Parkinson's disease (PD) is an etiologically heterogeneous disorder characterized by parkinsonism (bradykinesia, resting tremor, rigidity, and postural instability) with good response to L-dopa. PD is the second most prevalent neurodegenerative disorder after Alzheimer disease. Although the majority of PD cases are sporadic, 5-10% of PD is monogenic form of PD as familial PD (FPD). ⋯ Based on the variability, multifunction of LRRK2 such as phosphorylation of other proteins, especially, alpha-synuclein and tau, have been suggested. As interaction of Parkin and LRRK2 was reported, interaction and intersection among the autosomal-recessive or autosomal-dominant PD proteins could be involved in some common pathways, and LRRK2 may play an important role as a key FPD gene product. Identification of PARK8 and LRRK2 has given meaningful insights in not only PD but also numerous neurodegenerative disorders such as synucleinopathies and tauopathies with or without Lewy bodies.
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Neuropathic pain is often a consequence of nerve injury through surgery, bone compression, diabetes or infection. This type of pain can be so severe that even light touching can be intensely painful. Unfortunately, this state is generally resistant to currently available treatments. ⋯ The activated microglia express P2X4 after nerve injury, which can be stimulated by endogenous ATP, resulting in the release of BDNF which is one of key molecules involving in neuropathic pain. The microglia also express many molecules that were reported to be connected in the pain. Understanding the key roles of these ATP receptors in microglia may lead to new strategies for the management of intractable chronic pain.
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Increasing evidence indicates the importance of neuron-astrocyte interaction in synaptic function. However, structural evidence is scarce compared to abundant information from electrophysiological studies. Meticulous studies using serial electron microscopic technique in hippocampal CAI and cerebellum provided the earliest knowledge about three-dimensional close relationship between synapses and glial processes. ⋯ In the next step any astrocytic structural changes around mature synapses correlated with plastic change of synaptic efficacy, such as long-term potentiation, should be investigated. Structural relationship between axon terminals and astrocytic processes should also be revealed. Furthermore, in vivo time-lapse imaging of synapseastrocyte pairs will soon be accomplished, as techniques of in vivo two-photon imaging showed remarkable progress recently.