Alteration of somatosensory response in adulthood by early life stress

Early-life stress is well known as a critical risk factor for mental and cognitive disorders in adulthood. Such disorders are accompanied by altered neuro- (synapto-) genesis and gene expression. Because psychosomatic disorders induced by early-life stress (e.g., physical and/or sexual abuse, and neglect) have become a socio-economic problem, it is very important to clarify the mechanisms underlying these changes. However, despite of intensive clinical and animal studies, such mechanisms have not yet been clarified. Although the disturbance of glucocorticoid and glutamate homeostasis by stress has been well documented, it has not yet been clarified whether such disturbance by early-life stress persists for life. Furthermore, since previous studies have focused on the detection of changes in specific brain regions, such as the hippocampus and prefrontal cortex, it has not been clarified whether early-life stress induced changes in the sensory/motor system. Thus, in this review, we introduce recent studies on functional/structural changes in the somatosensory cortex induced by early-life stress. We believe that this review provides new insights into the functional alteration of the somatosensory system induced by early-life stress. Such information may have clinical relevance in terms of providing effective therapeutic interventions to early-life-stressed individuals

Studi Meta-Analisis: Hubungan antara Defisiensi Vitamin D dan Penyakit Parkinson

Beberapa penelitian telah dilakukan untuk mengevaluasi kadar 25(OH)D pada pasien penyakit Parkinson. Namun, hasil penelitian ini tidak konsisten. Penelitian ini melakukan meta-analisis terhadap kadar 25(OH)D pada pasien dengan penyakit Parkinson. Database PubMed digunakan untuk melakukan pencarian literatur secara sistematis. Meta-analisis dilakukan dengan menggunakan model efek acak untuk menghitung perkiraan efek gabungan. Tujuh belas artikel dimasukkan dalam penelitian ini. Meta-analisis mengungkapkan bahwa pasien dengan penyakit Parkinson memiliki kadar 25(OH)D yang lebih rendah dibandingkan dengan kontrol. Temuan dari artikel prospektif dan retrospektif sebagian besar konsisten. Besarnya respon nocebo dalam uji coba terkontrol acak yang dirancang paralel pada penyakit Parkinson sangat penting dan harus dipertimbangkan dalam interpretasi hasil keamanan dan dalam desain dan interpretasi uji klinis masa depan.

Aberrant Cerebellar Development in Mice Lacking Dual Oxidase Maturation Factors

Background: Thyroid hormone (TH) plays a key role in the developing brain, including the cerebellum. TH deficiency induces organizational changes of the cerebellum, causing cerebellar ataxia. However, the mechanisms causing these abnormalities are poorly understood. Various animal models have been used to study the mechanism. Lacking dual oxidase (DUOX) and its maturation factor (DUOXA) are major inducers of congenital hypothyroidism. Thus, this study examined the organizational changes of the cerebellum using knockout mice of the Duoxa gene (Duoxa?/?). Methods: The morphological, behavioral, and electrophysiological changes were analyzed in wild type (Wt) and Duoxa-deficient (Duoxa?/?) mice from postnatal day (P) 10 to P30. To detect the changes in the expression levels of presynaptic proteins, Western blot analysis was performed. Results: The proliferation and migration of granule cells was delayed after P15 in Duoxa?/? mice. However, these changes disappeared by P25. Although the cerebellar structure of Duoxa?/? mice was not significantly different from that of Wt mice at P25, motor coordination was impaired. It was also found that the amplitude of paired-pulse facilitation at parallel fiber?Purkinje cell synapses decreased in Duoxa?/? mice, particularly at P15. There were no differences between expression levels of presynaptic proteins regulating neurotransmitter release at P25. Conclusions: These results indicate that the anatomical catch-up growth of the cerebellum did not normalize its function because of the disturbance of neuronal circuits by the combined effect of hypothyroidism and functional disruption of the DUOX/DUOXA complex.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140263/1/thy.2015.0034.pd

Thyroid hormone in brain and brain cells

Editorial.-- This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).Peer Reviewe

COUP-TFII in Kidneys, from Embryos to Sick Adults

Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) is an orphan nuclear hormone receptor of unknown ligands. This molecule has two interesting features: (1) it is a developmental gene, and (2) it is a potential hormone receptor. Here, we describe the possible roles of COUP-TFII in the organogenesis of the kidneys and protection from adult renal diseases, primarily in mouse models. COUP-TFII is highly expressed in embryos, including primordial kidneys, and is essential for the formation of metanephric mesenchyme and the survival of renal precursor cells. Although the expression levels of COUP-TFII are low and its functions are unknown in healthy adults, it serves as a reno-protectant molecule against acute kidney injury. These are good examples of how developmental genes exhibit novel functions in the etiology of adult diseases. We also discuss the ongoing research on the roles of COUP-TFII in podocyte development and diabetic kidney disease. In addition, the identification of potential ligands suggests that COUP-TFII might be a novel therapeutic target for renal diseases in the future

The effect of soy isoflavones in brain development: the emerging role of multiple signaling pathways and future perspectives

Soybean is a source of protein, fibers, and phytochemical isoflavones which are considered to have numerous health benefits for children and adulthood. On the other hand, isoflavones are widely known as phytoestrogens that exert their action via the estrogen signaling pathway. With this regard, isoflavones are also considered as endocrine-disrupting chemicals. Endogenous estrogen plays a crucial role in brain development through binding to estrogen receptors (ERs) or G protein-coupled estrogen receptors 1 (GPER1) and regulates morphogenesis, migration, functional maturation, and intracellular metabolism of neurons and glial cells. Soy isoflavones can also bind to ERs, GPER1, and, furthermore, other receptors to modulate their action. Therefore, soy isoflavone consumption may affect brain development during the pre-and post-natal periods. This review summarizes the current knowledge on the mechanisms of isoflavone action, particularly in the early stages of brain development by introducing representative human, and animal models, and in vitro studies, and discusses their beneficial and adverse impact on neurobehavior. As a conclusion, the soy product consumption during the pre-and post-natal periods under proper range of dose showed beneficial effects in neurobehavior development, including improvement of anxiety, aggression, hyperactive behavior, and cognition, whereas their adverse effect by taking higher doses cannot be excluded. We also present novel research lines to further assess the effect of soy isoflavone administration during brain development

Suppression of Thyroid Hormone Receptor-Mediated Transcription by Methamidophos

Methamidophos is a cholinesterase inhibitor organophosphate (OP) used commonly as a pesticide. Its use is currently a global concern due to widespread occurrence, persistence, bioaccumulation and neurotoxic potential. We therefore examined the effect of methamidophos on thyroid hormone receptor (TR)-mediated gene expression using transient transfection-based reporter gene assay. Our results shows that methamidophos (10-6 M) suppressed thyroid hormone (TH)-induced TR-mediated transcription. We further examined the effects of methamidophos on TR-thyroid hormone response element (TRE) binding using the liquid chemiluminescent DNA pull-down assay (LCDPA), and found no dissociation of TR from TRE. Using mammalian two hybrid assay, we showed that methamidophos did not recruit co-activator (steroid receptor co-activator 1; SRC-1) to TR in the presence of TH. Also, it did not recruit co-repressors (nuclear co-repressor; NCoR) to TR in the absence of TH at all concentrations examined. The effects of methamidophos on cerebellar Purkinje cell dendritogenesis, granule cell neurite morphology and synaptic plasticity are currently under investigation. Taken together, our results show that methamidophos can potentially disrupt TR–mediated gene expression, suggesting that methamidophos may interfere with thyroid hormone-mediated activities in various target organs including the developing brain