GABA and Glutamate: Their Transmitter Role in the CNS and Pancreatic Islets

Glutamate and gamma-aminobutyric acid (GABA) are the major neurotransmitters in the mammalian brain. Inhibitory GABA and excitatory glutamate work together to control many processes, including the brain’s overall level of excitation. The contributions of GABA and glutamate in extra-neuronal signaling are by far less widely recognized. In this chapter, we first discuss the role of both neurotransmitters during development, emphasizing the importance of the shift from excitatory to inhibitory GABAergic neurotransmission. The second part summarizes the biosynthesis and role of GABA and glutamate in neurotransmission in the mature brain, and major neurological disorders associated with glutamate and GABA receptors and GABA release mechanisms. The final part focuses on extra-neuronal glutamatergic and GABAergic signaling in pancreatic islets of Langerhans, and possible associations with type 1 diabetes mellitus

The Inventory of Personality Organisation: its psychometric properties among student and clinical populations in Japan

<p>Abstract</p> <p>Background</p> <p>The Inventory of Personality Organisation (IPO) is a self-report measure that reflects personality traits, as theorised by Kernberg.</p> <p>Methods</p> <p>In study 1, the Japanese version of the IPO was distributed to a population of Japanese university students (N = 701). The students were randomly divided into two groups. The factor structure derived from an exploratory factor analysis among one subsample was tested using a confirmatory factor structure among another subsample. In study 2, the factor-driven subscales of the IPO were correlated with other variables that would function as external criteria to validate the scale in a combined population of the students used in study 1 and psychiatric outpatients (N = 177).</p> <p>Results</p> <p>In study 1 the five-factor structure presented by the original authors was replicated in exploratory factor analyses in one subgroup of students. However, this was through reduction of the number of items (the number of the primary items was reduced from 57 to 24 whereas the number of the additional items was reduced from 26 to 13) due to low endorsement frequencies as well as low factor loadings on a designated factor. The new factor structure was endorsed by a confirmatory factor analysis in the other student subgroup. In study 2 the new five subscales of the Japanese IPO were likely to be correlated with younger age, more personality psychopathology (borderline and narcissistic), more dysphoric mood, less psychological well-being, more insecure adult attachment style, lower self-efficacy, and more frequent history of childhood adversity. The IPO scores were found to predict the increase in suicidal ideation in a week's time in a longitudinal follow-up.</p> <p>Conclusion</p> <p>Although losing more than 40% of the original items, the Japanese IPO may be a reliable and valid measure of Kernberg's personality organisation for Japanese populations.</p

A Clinical Trial of Kampo Formulae for the Treatment of Symptoms of Yusho, a Poisoning Caused by Dioxins and Related Organochlorine Compounds

The objective of this study was to evaluate the effectiveness of traditional herbal medicines (Kampo) on the symptoms of Yusho. Yusho is a mass food poisoning that was caused by ingestion of rice oil contaminated with dioxins and related organochlorines in 1968. Patients with Yusho suffer from skin symptoms (acneform eruptions, liability to suppuration and pigmentation), respiratory symptoms (cough and expectoration of sputum), neurological symptoms (numbness and paresthesia of extremities), arthralgia and general fatigue, and no effective treatment has yet been developed. In this clinical trial, four Kampo formulae (Bakumondo-to, Keigai-rengyo-to, Gosha-jinki-gan and Hochu-ekki-to) were administered to four representative Yusho symptoms (respiratory, skin, neurological symptoms and general fatigue), respectively. Twenty-seven Yusho patients were enrolled and two formulae were administered to each patient for half-a-year each. The effectiveness of Kampo formulae was estimated by changes in the intensity of symptoms measured by a visual analogue scale (VAS) of 100 mm recorded at baseline and after administration of each formula. The influence of Kampo formulae on patients' quality of life (QOL) was also assessed by the SF-36 (NBS). Twenty-five patients completed the treatment. Bakumondo-to significantly improved respiratory symptoms as well as patients' QOL in the context of vitality, compared with other formulae. In contrast, Hochu-ekki-to impaired patients' QOL in the context of physical functioning and vitality, compared with other formulae. This study demonstrated for the first time that a Kampo formula Bakumondo-to is useful for treating respiratory symptoms caused by dioxins

Quantitative Assessment of Gait Bradykinesia in Parkinson’s Disease Using a Portable Gait Rhythmogram

To quantify gait bradykinesia during daily activity in patients with Parkinson's disease (PD), we measured movement-induced accelerations over more than 24h in 50 patients with PD and 17 age-matched normal controls, using a new device, the portable gait rhythmogram. Acceleration values induced by various movements, averaged each 10 min, exhibited a gamma distribution. The mean value of the distribution curve was used as an index of the "amount of overall movement per 24h". Characteristic changes were observed in both the gait cycle and gait acceleration. During hypokinesia, the gait cycle became either faster or slower. A number of patients with marked akinesia/bradykinesia showed a reduced and narrow range of gait acceleration, i.e., a range of floor reaction forces. The results suggest that assessment of the combination of changes in gait cycle and gait acceleration can quantitatively define the severity of gait bradykinesia

CLASSIFICATION OF BIPOLAR DISORDER, MAJOR DEPRESSIVE DISORDER, AND HEALTHY STATE USING VOICE

Objective: In this study, we propose a voice index to identify healthy individuals, patients with bipolar disorder, and patients with major depressive disorder using polytomous logistic regression analysis.Methods: Voice features were extracted from voices of healthy individuals and patients with mental disease. Polytomous logistic regression analysis was performed for some voice features.Results: With the prediction model obtained using the analysis, we identified subject groups and were able to classify subjects into three groups with 90.79% accuracy.Conclusion: These results show that the proposed index may be used as a new evaluation index to identify depression

A Proposal for New Algorithm that Defines Gait-Induced Acceleration and Gait Cycle in Daily Parkinsonian Gait Disorders

We developed a new device, the portable gait rhythmogram (PGR), to record up to 70 hrs of movement-induced accelerations. Acceleration values induced by various movements, averaged every 10 min, showed gamma distribution, and the mean value of this distribution was used as an index of the amount of overall movements. Furthermore, the PGR algorithm can specify gait-induced accelerations using the pattern-matching method. Analysis of the relationship between gait-induced accelerations and gait cycle duration makes it possible to quantify Parkinson’s disease (PD)-specific pathophysiological mechanisms underlying gait disorders. Patients with PD showed the following disease-specific patterns: (1) reduced amount of overall movements and (2) low amplitude of gait-induced accelerations in the early stages of the disease, which was compensated by fast stepping. Loss of compensation was associated with slow stepping gait, (3) narrow range of gait-induced acceleration amplitude and gait cycle duration, suggesting monotony, and (4) evident motor fluctuations during the day by tracing changes in the above two parameters. Prominent motor fluctuation was associated with frequent switching between slow stepping mode and active mode. These findings suggest that monitoring various movement- and gait-induced accelerations allows the detection of specific changes in PD. We conclude that continuous long-term monitoring of these parameters can provide accurate quantitative assessment of parkinsonian clinical motor signs

Medical and Paramedical Care of Patients With Cerebellar Ataxia During the COVID-19 Outbreak: Seven Practical Recommendations of the COVID 19 Cerebellum Task Force

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), the cause of the current pandemic coronavirus disease 2019 (COVID-19), primarily targets the respiratory system. Some patients also experience neurological signs and symptoms ranging from anosmia, ageusia, headache, nausea, and vomiting to confusion, encephalitis, and stroke. Approximately 36% of those with severe COVID-19 experience neurological complications. The virus may enter the central nervous system through the olfactory nerve in the nasal cavity and damage neurons in the brainstem nuclei involved in the regulation of respiration. Patients with cerebellar ataxia (CA) are particularly vulnerable to severe outcome if they contract COVID-19 because of the complexity of their disease, the presence of comorbidities, and their use of immunosuppressive therapies. Most CA patients burdened by progressive neurologic deficits have substantially impaired mobility and other essential functions, for which they rely heavily on ambulatory services, including rehabilitation and psychosocial care. Cessation of these interventions because of isolation restrictions places the CA patient population at risk of further deterioration. This international panel of ataxia experts provides recommendations for neurologists caring for patients with CA, emphasizing a pro-active approach designed to maintain their autonomy and well-being: continue long-term medications, promote rehabilitation efforts, utilize the technology of virtual visits for regular contact with healthcare providers, and pay attention to emotional and psychosocial health. Neurologists should play an active role in decision-making in those CA cases requiring escalation to intensive care and resuscitation. Multi-disciplinary collaboration between care teams is always important, and never more so than in the context of the current pandemic

Disease-specific monoclonal antibodies targeting glutamate decarboxylase impair GABAergic neurotransmission and affect motor learning and behavioral functions

Autoantibodies to the smaller isoform of glutamate decarboxylase (GAD) can be found in patients with type 1 diabetes and a number of neurological disorders, including stiff-person syndrome, cerebellar ataxia and limbic encephalitis. The detection of disease-specific autoantibody epitopes led to the hypothesis that distinct GAD autoantibodies may elicit specific neurological phenotypes. We explored the in vitro/in vivo effects of well-characterized monoclonal GAD antibodies. We found that GAD autoantibodies present in patients with stiff person syndrome (n = 7) and cerebellar ataxia (n = 15) recognized an epitope distinct from that recognized by GAD autoantibodies present in patients with type 1 diabetes mellitus (n = 10) or limbic encephalitis (n = 4). We demonstrated that the administration of a monoclonal GAD antibody representing this epitope specificity; (1) disrupted in vitro the association of GAD with γ-Aminobutyric acid containing synaptic vesicles; (2) depressed the inhibitory synaptic transmission in cerebellar slices with a gradual time course and a lasting suppressive effect; (3) significantly decreased conditioned eyelid responses evoked in mice, with no modification of learning curves in the classical eyeblink-conditioning task; (4) markedly impaired the facilitatory effect exerted by the premotor cortex over the motor cortex in a paired-pulse stimulation paradigm; and (5) induced decreased exploratory behavior and impaired locomotor function in rats. These findings support the specific targeting of GAD by its autoantibodies in the pathogenesis of stiff-person syndrome and cerebellar ataxia. Therapies of these disorders based on selective removal of such GAD antibodies could be envisioned.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

The Classification of Autosomal Recessive Cerebellar Ataxias : a Consensus Statement from the Society for Research on the Cerebellum and Ataxias Task Force

There is currently no accepted classification of autosomal recessive cerebellar ataxias, a group of disorders characterized by important genetic heterogeneity and complex phenotypes. The objective of this task force was to build a consensus on the classification of autosomal recessive ataxias in order to develop a general approach to a patient presenting with ataxia, organize disorders according to clinical presentation, and define this field of research by identifying common pathogenic molecular mechanisms in these disorders. The work of this task force was based on a previously published systematic scoping review of the literature that identified autosomal recessive disorders characterized primarily by cerebellar motor dysfunction and cerebellar degeneration. The task force regrouped 12 international ataxia experts who decided on general orientation and specific issues. We identified 59 disorders that are classified as primary autosomal recessive cerebellar ataxias. For each of these disorders, we present geographical and ethnical specificities along with distinctive clinical and imagery features. These primary recessive ataxias were organized in a clinical and a pathophysiological classification, and we present a general clinical approach to the patient presenting with ataxia. We also identified a list of 48 complex multisystem disorders that are associated with ataxia and should be included in the differential diagnosis of autosomal recessive ataxias. This classification is the result of a consensus among a panel of international experts, and it promotes a unified understanding of autosomal recessive cerebellar disorders for clinicians and researchers