Elevated glutamine/glutamate ratio in cerebrospinal fluid of first episode and drug naive schizophrenic patients

BACKGROUND: Recent magnetic resonance spectroscopy (MRS) studies report that glutamine is altered in the brains of schizophrenic patients. There were also conflicting findings on glutamate in cerebrospinal fluid (CSF) of schizophrenic patients, and absent for glutamine. This study aims to clarify the question of glutamine and glutamate in CSF of first episode and drug naive schizophrenic patients. METHOD: Levels of glutamine and glutamate in CSF of 25 first episode and drug-naive male schizophrenic patients and 17 age-matched male healthy controls were measured by a high performance liquid chromatography. RESULTS: The ratio (126.1 (median), 117.7 ± 27.4 (mean ± S.D.)) of glutamine to glutamate in the CSF of patients was significantly (z = -3.29, p = 0.001) higher than that (81.01 (median), 89.1 ± 22.5 (mean ± S.D.)) of normal controls although each level of glutamine and glutamate in patients was not different from that of normal controls. CONCLUSION: Our data suggests that a disfunction in glutamate-glutamine cycle in the brain may play a role in the pathophysiology of schizophrenia

Keratinocytes as Depository of Ammonium-Inducible Glutamine Synthetase: Age- and Anatomy-Dependent Distribution in Human and Rat Skin

In inner organs, glutamine contributes to proliferation, detoxification and establishment of a mechanical barrier, i.e., functions essential for skin, as well. However, the age-dependent and regional peculiarities of distribution of glutamine synthetase (GS), an enzyme responsible for generation of glutamine, and factors regulating its enzymatic activity in mammalian skin remain undisclosed. To explore this, GS localization was investigated using immunohistochemistry and double-labeling of young and adult human and rat skin sections as well as skin cells in culture. In human and rat skin GS was almost completely co-localized with astrocyte-specific proteins (e.g. GFAP). While GS staining was pronounced in all layers of the epidermis of young human skin, staining was reduced and more differentiated among different layers with age. In stratum basale and in stratum spinosum GS was co-localized with the adherens junction component ß-catenin. Inhibition of, glycogen synthase kinase 3β in cultured keratinocytes and HaCaT cells, however, did not support a direct role of ß-catenin in regulation of GS. Enzymatic and reverse transcriptase polymerase chain reaction studies revealed an unusual mode of regulation of this enzyme in keratinocytes, i.e., GS activity, but not expression, was enhanced about 8–10 fold when the cells were exposed to ammonium ions. Prominent posttranscriptional up-regulation of GS activity in keratinocytes by ammonium ions in conjunction with widespread distribution of GS immunoreactivity throughout the epidermis allows considering the skin as a large reservoir of latent GS. Such a depository of glutamine-generating enzyme seems essential for continuous renewal of epidermal permeability barrier and during pathological processes accompanied by hyperammonemia

The Cerebellum, Cerebellar Disorders, and Cerebellar Research—Two Centuries of Discoveries

Research on the cerebellum is evolving rapidly. The exquisiteness of the cerebellar circuitry with a unique geometric arrangement has fascinated researchers from numerous disciplines. The painstaking works of pioneers of these last two centuries, such as Rolando, Flourens, Luciani, Babinski, Holmes, Cajal, Larsell, or Eccles, still exert a strong influence in the way we approach cerebellar functions. Advances in genetic studies, detailed molecular and cellular analyses, profusion of brain imaging techniques, emergence of behavioral assessments, and reshaping of models of cerebellar function are generating an immense amount of knowledge. Simultaneously, a better definition of cerebellar disorders encountered in the clinic is emerging. The essentials of a trans-disciplinary blending are expanding. The analysis of the literature published these last two decades indicates that the gaps between domains of research are vanishing. The launch of the society for research on the cerebellum (SRC) illustrates how cerebellar research is burgeoning. This special issue gathers the contributions of the inaugural conference of the SRC dedicated to the mechanisms of cerebellar function. Contributions were brought together around five themes: (1) cerebellar development, death, and regeneration; (2) cerebellar circuitry: processing and function; (3) mechanisms of cerebellar plasticity and learning; (4) cerebellar function: timing, prediction, and/or coordination? (5) anatomical and disease perspectives on cerebellar function.Historical ArticleJournal ArticleReviewSCOPUS: re.jinfo:eu-repo/semantics/publishe