Basal ganglia as a sensory gating devise for motor control

Basal ganglia lie between the cerebral cortex and the thalamus, and have dense fiber connections between them. These connections form 4-5 distinct loops or circuits to allow parallel processing of information. Among them, the most intensively studied is the motor loop, which comprises 2 distinct direct and indirect pathways. The direct pathway disinhibits the powerful inhibition of the internal segment of the globus pallidus/substantia nigra pars reticulata upon thalamic ventrolateral nuclei with a net result of facilitatory influence upon the motor cortex. By contrast, the indirect pathway exerts an inhibitory effect. Overall this dual system provides a center (excitatory)-surround (inhibitory) mechanism to focus its effect on selected cortical neurons. Although putative transmitters, inhibitory or excitatory nature of these projections and their receptors are mostly known, the functional role of the loop in motor control is not precisely understood. Several lines of evidence have recently been presented to support the view that this center-surround mechanism is used to focus the output to a specific group of muscles required for performing a specific task. This operation is made possible through opening the sensory channel for the expected sensory feed-back afferents during movement. Thus one of the important functions of basal ganglia seems to be the gating of sensory input for motor control

トウニョウビョウセイ ニューロパチー ニオケル ジクサク イオン チャンネル キノウ

Diabetic neuropathy is characterized by the early decrease in motor conduction velocities and loss of vibratory sense. Autonomic dysfuncion may also be present in the early stage. These clinical features are not explainted by demyelination or Wallerian degeneration. Threshold tracking techniques such as latent addition or threshold electrotonus have been developed to explore the function of the ion channels non-invasively. Decreased peak Na current was found in diabetic patients, and is correlated with the decreased in motor conduction velocities. In ward rectifiers, which counteract membrane hyperpolatization, were found deficient in diabetic patients and models. This may lead to frequency-dependent conduction block, thus accounting for the early loss of vibratory sense. These clinical tests of axonal function is expected to reveal physiological information which the conventional nerve conduction studies could not provide previously

Clinicopathological Phenotype and Genetics of X-Linked Dystonia–Parkinsonism (XDP; DYT3; Lubag)

X-linked dystonia–parkinsonism (XDP; OMIM314250), also referred to as DYT3 dystonia or “Lubag” disease, was first described as an endemic disease in the Philippine island of Panay. XDP is an adult-onset movement disorder characterized by progressive and severe dystonia followed by overt parkinsonism in the later years of life. Among the primary monogenic dystonias, XDP has been identified as a transcriptional dysregulation syndrome with impaired expression of the TAF1 (TATA box-binding protein associated factor 1) gene, which is a critical component of the cellular transcription machinery. The major neuropathology of XDP is progressive neuronal loss in the neostriatum (i.e., the caudate nucleus and putamen). XDP may be used as a human disease model to elucidate the pathomechanisms by which striatal neurodegeneration leads to dystonia symptoms. In this article, we introduce recent advances in the understanding of the interplay between pathophysiology and genetics in XDP

Sensitive immunohistochemistry for autopsied brain

Immunohistochemistry (IHC) is a valuable method for identifying discrete neurochemical molecules by the interaction of target antigens with validated antibodies tagged with a visible label (e.g., peroxidase). We have developed an immunostaining method that is highly sensitive in detection of neurochemical antigens. Our IHC method, which we call the PBTA method, involves a hybrid protocol that implements aspects of both the polymer and avidin-biotin-complex (ABC) methods in combination with biotin-tyramide amplification. When using [Met]-enkephalin as a target antigen, the sensitivity of the PBTA method for IHC was more than 100-fold higher compared with the polymer and ABC methods. In addition, its sensitivity for enzyme-linked immunosorbent assay was about 1,000-fold higher compared with the ABC method. We examined the utility of our IHC method for both chromogenic and fluorescence detection systems used to visualize neurochemical peptides and proteins in formalin-fixed, paraffin-embedded tissues from autopsied human brains. The results convincingly demonstrate that under optimal conditions, our IHC method is highly sensitive without increasing non-specific background activities. Our IHC method could be a powerful tool for detection and visualization of neurochemical antigens that are present even in trace amounts in autopsied human brains

DBS for Tardive Syndrome

Tardive syndrome (TDS) is a potentially permanent and irreversible hyperkinetic movement disorder caused by exposure to dopamine receptor blocking agents. Guidelines published by the American Academy of Neurology recommend pharmacological first-line treatment for TDS with clonazepam (level B), ginkgo biloba (level B), amantadine (level C), and tetrabenazine (level C). Recently, a class II study provided level C evidence for use of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in patients with TDS. Although the precise pathogenesis of TDS remains to be elucidated, the beneficial effects of GPi-DBS in patients with TDS suggest that the disease may be a basal ganglia disorder. In addition to recent advances in understanding the pathophysiology of TDS, this article introduces the current use of DBS in the treatment of medically intractable TDS

The effect of istradefylline for Parkinson’s disease : A meta-analysis

Adenosine A2A receptor antagonists are an alternative treatment strategy for Parkinson’s disease. Several randomized placebo controlled studies have tested the effect of A2A receptor antagonist istradefylline, and more robust evidence has been acquired. This meta-analysis aimed to provide evidence for its efficacy and safety on patients with Parkinson’s disease. After a systematic literature search, we calculated the pooled standardized mean difference and risk ratio for continuous and dichotomous variables, respectively. Further, sensitivity analyses were performed to confirm the effect estimated by meta-analyses. Publication bias was assessed by funnel plot and deviation of intercept. Six studies satisfied our inclusion criteria. Istradefylline (40 mg/day) decreased off time and improved motor symptoms of Parkinson’s disease in homogeneous studies. Istradefylline at 20 mg/day decreased off time and improved motor symptoms, but heterogeneity was found in the analysis of the former among studies. There was a significant effect of istradefylline on dyskinesia in homogeneous studies. Publication bias, however, was observed in the comparison of dyskinesia. Other adverse events showed no significant difference. The present meta-analysis suggests that istradefylline at 40 mg/day could alleviate off time and motor symptoms derived from Parkinson’s disease. Dyskinesia might be worsened, but publication bias prevents this from being clear