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Neural receptor dysfunction

Qing Mu, Weidong Yu, Shuying Zheng, Hongxia Shi, Mei Li, Jie Sun, Di Wang, Xiaoli Hou, Ling Liu, Xinjuan Wang, Zhuran Zhao, Rong Liang, Xue Zhang, Wei Dong, Chaomei Zeng, Jingzhu Guo
Vitamin A deficiency and mitochondrial dysfunction are both associated with neural differentiation-related disorders, such as Alzheimer's disease (AD) and Down syndrome (DS). The mechanism of vitamin A-induced neural differentiation and the notion that vitamin A can regulate the morphology and function of mitochondria in its induction of neural differentiation through the RIP140/PGC-1α axis are unclear. The aim of this study was to investigate the roles and underlying mechanisms of RIP140/PGC-1α axis in vitamin A-induced neural differentiation...
March 7, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Alireza Mohammadi, Vahid Ghasem Amooeian, Ehsan Rashidi
Brain-derived neurotrophic factor (BDNF) is a dominant neurotrophic factor in the brain which plays a crucial role in differentiation, regeneration and plasticity mechanisms. Binding of the BDNF to its high-affinity tropomyosin-related kinase B (TrkB) receptor leads to phosphorylation of TrkB, thus activating the three important downstream intracellular signaling cascades within the neural cells including phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), phospholipase C-γ (PLCγ), and mitogen-activated protein kinase/extracellular signal related kinase (MAPK/ERK) pathways...
March 2, 2018: Current Gene Therapy
Atsukazu Kuwahara, Yuko Kuwahara, Toshio Inui, Yoshinori Marunaka
The diffuse chemosensory system (DCS) is well developed in the apparatuses of endodermal origin like gastrointestinal (GI) tract. The primary function of the GI tract is the extraction of nutrients from the diet. Therefore, the GI tract must possess an efficient surveillance system that continuously monitors the luminal contents for beneficial or harmful compounds. Recent studies have shown that specialized cells in the intestinal lining can sense changes in the luminal content. The chemosensory cells in the GI tract belong to the DCS which consists of enteroendocrine and related cells...
March 5, 2018: International Journal of Molecular Sciences
Anand M Bokare, Mandar Bhonde, Rajan Goel, Yogendra Nayak
RATIONALE AND OBJECTIVES: 5-HT6 receptors are mainly expressed in brain areas associated with learning and memory. Several studies have reported procognitive effects of both 5-HT6 agonist and antagonists. However, the exact mechanism 5-HT6 receptor modulation has not been properly studied especially in the context of cholinergic functions, cerebral blood flow (CBF), brain-derived neural factor (BDNF), oxidative stress, and behavioral changes. METHODS: In the present study, memory impairment was induced in albino Wistar rats by two doses of intracerebroventricular (ICV) injection of streptozotocin (STZ, 3 mg/kg) on first and third day...
March 3, 2018: Psychopharmacology
Srinivasan ThyagaRajan, Lalgi Hima, Uday P Pratap, Hannah P Priyanka, Ramasamy Vasantharekha
Reproductive aging in females is marked by alterations in gonadal hormones, estrogen and progesterone, that facilitate cessation of reproductive cycles and onset of female-specific diseases such as autoimmune and neurodegenerative diseases, hormone-dependent cancers, and osteoporosis. Bidirectional communication between the three homeostatic systems, nervous system, endocrine system, and immune system, is essential for the maintenance of health and any dysfunction in the cross-talk promotes the development of diseases and cancer...
February 22, 2018: Journal of Chemical Neuroanatomy
Ting Sun, Yu-Jiao Li, Qin-Qin Tian, Qi Wu, Dan Feng, Zhe Xue, Yan-Yan Guo, Le Yang, Kun Zhang, Ming-Gao Zhao, Yu-Mei Wu
Chronic cerebral hypoperfusion (CCH), a leading cause of various cerebrovascular diseases, leads to cognitive dysfunction due to neuron loss and impaired neurogenesis. Liver X receptors (LXRs), including LXRα and LXRβ isoforms, are crucial for cholesterol metabolism, synaptic plasticity as well as neurogenesis. However, it is not clear the potential roles of LXRs in the pathogenesis of cognitive impairment induced by CCH. In this study, we demonstrated that LXRβ expression decreased in hippocampus of CCH mice...
February 12, 2018: Experimental Neurology
Dehua Liao, Yujin Guo, Daxiong Xiang, Ruili Dang, Pengfei Xu, Hualin Cai, Lizhi Cao, Pei Jiang
Objective: Long-term use of doxorubicin (Dox) can cause neurobiological side effects associated with depression, but the underlying mechanisms remain equivocal. While recent evidence has indicated that Neuregulin-1 (NRG1) and its ErbB receptors play an essential role in neural function, much is still unknown concerning the biological link between the NRG1/ErbB pathway and the Dox-induced neurotoxicity. Therefore, we examined the protein expression of NRG1 and ErbB receptors in the hippocampus of rats following Dox treatment...
2018: Drug Design, Development and Therapy
Pablo Garrido-Gil, Ana I Rodriguez-Perez, Antonio Dominguez-Meijide, Maria J Guerra, Jose L Labandeira-Garcia
The exact mechanism of gut dysfunction in Parkinson's disease and, conversely, the role of gut pathology in brain dopaminergic degeneration are controversial. We investigated the effects of nigral lesions on the colonic neurotransmission, the effect of gut inflammation on the nigrostriatal dopaminergic function, and the possible involvement of the vagus nerve and the local renin-angiotensin system (RAS). Nigrostriatal dopamine depletion was performed by bilateral injection 6-hydroxydopamine, and gut inflammation was induced by dextran sulfate sodium salt treatment in rats and mice, respectively, with or without vagal disruption...
February 5, 2018: Molecular Neurobiology
Yan-Yun Liu, Gregory A Brent
Thyroid hormone (TH) is essential for normal brain development and may also promote recovery and neuronal regeneration after brain injury. TH acts predominantly through the nuclear receptors, TH receptor alpha (THRA) and beta (THRB). Additional factors that impact TH action in the brain include metabolism, activation of thyroxine (T4) to triiodothyronine (T3) by the enzyme 5'-deiodinase Type 2 (Dio2), inactivation by the enzyme 5-deiodinase Type 3 (Dio3) to reverse T3 (rT3), which occurs in glial cells, and uptake by the Mct8 transporter in neurons...
February 8, 2018: Pharmacology & Therapeutics
Si-Qiang Ren, Wen Yao, Jing-Zhi Yan, Chunhui Jin, Jia-Jun Yin, Jianmin Yuan, Shui Yu, Zaohuo Cheng
Alzheimer's disease (AD) is the most common cause of dementia in the elderly. At the early stages of AD development, the soluble β-amyloid (Aβ) induces synaptic dysfunction, perturbs the excitation/inhibition balance of neural circuitries, and in turn alters the normal neural network activity leading to cognitive decline, but the underlying mechanisms are not well established. Here by using whole-cell recordings in acute mouse brain slices, we found that 50 nM Aβ induces hyperexcitability of excitatory pyramidal cells in the cingulate cortex, one of the most vulnerable areas in AD, via depressing inhibitory synaptic transmission...
January 10, 2018: Scientific Reports
Maria G Zizzo, Monica Frinchi, Domenico Nuzzo, Hyder A Jinnah, Giuseppa Mudò, Daniele F Condorelli, Francesco Caciagli, Renata Ciccarelli, Patrizia Di Iorio, Flavia Mulè, Natale Belluardo, Rosa Serio
Mutations in the HGPRT1 gene, which encodes hypoxanthine-guanine phosphoribosyltransferase (HGprt), housekeeping enzyme responsible for recycling purines, lead to Lesch-Nyhan disease (LND). Clinical expression of LND indicates that HGprt deficiency has adverse effects on gastrointestinal motility. Therefore, we aimed to evaluate intestinal motility in HGprt knockout mice (HGprt¯). Spontaneous and neurally evoked mechanical activity was recorded in vitro as changes in isometric tension in circular muscle strips of distal colon...
December 20, 2017: Autonomic Neuroscience: Basic & Clinical
Jingying Zhu, Songsong Zang, Xufeng Chen, Lei Jiang, Aihua Gu, Jie Cheng, Li Zhang, Jun Wang, Hang Xiao
Methamphetamine (Meth) is an illicit psychostimulant with high abuse potential and severe neurotoxicity. Recent studies have shown that dysfunctions in learning and memory induced by Meth may partially reveal the mechanisms of neuronal channelopathies. Kv2.1, the primary delayed rectifying potassium channel in neurons, is responsible for mediating apoptotic current surge. However, whether Kv2.1 is involved in Meth-mediated neural injury remains unknown. In the present study, the treatment of primary cultured hippocampal neurons with Meth indicated that Meth induced a time- and dose-dependent augmentation of Kv2...
January 3, 2018: Journal of Applied Toxicology: JAT
Sheng-Tien Li, Tai-Horng Young, Tsung-Wei Huang
Olfactory dysfunction significantly influences patients' life quality, but currently has no adequate treatment. Poly (ethylene-co-vinyl alcohol) (EVAL) mediates cell adhesion, growth and modulates differentiation of neural stem cells. However, whether EVAL is a suitable substrate to establish an in vitro culture system that can promote development and differentiation of human olfactory neuroepithelial cells (HONCs) remains unexplored. This study isolates and cultures HONCs on controls and EVAL films for 21 days...
December 26, 2017: Acta Biomaterialia
Shingo Nakajima, Mari Gotoh, Keiko Fukasawa, Hiromu Murofushi, Kimiko Murakami-Murofushi
Lysophosphatidic acid (LPA) and cyclic phosphatidic acid (cPA) are one of the lipid mediators regulating cell proliferation and differentiation through the activation of LPA receptors. An LPA receptor-mediated signal is important for the development of the central nervous system, while it has been demonstrated that LPA caused microglial activation and astroglial dysfunction. Previously, we have reported that cPA and carba analog of cPA, 2-O-carba-cPA (2ccPA), protected neural damage caused by transient ischemia...
December 23, 2017: Brain Research
Sora Shin, Horia Pribiag, Varoth Lilascharoen, Daniel Knowland, Xiao-Yun Wang, Byung Kook Lim
Early life stress (ELS) in the form of child abuse/neglect is associated with an increased risk of developing social dysfunction in adulthood. Little is known, however, about the neural substrates or the neuromodulatory signaling that govern ELS-induced social dysfunction. Here, we show that ELS-induced downregulation of dopamine receptor 3 (Drd3) signaling and its corresponding effects on neural activity in the lateral septum (LS) are both necessary and sufficient to cause social abnormalities in adulthood...
December 14, 2017: Neuron
A Ahnaou, H Huysmans, T Van de Casteele, W H I M Drinkenburg
Oscillatory activity in the gamma frequency range is a critical mechanism, which integrates neural networks within and across brain structures during cognitive processes. In schizophrenia, abnormalities in high gamma oscillations are ubiquitous and most likely reflect dysfunction in neuronal networks. In conscious rats, disturbed network oscillations associated with positive symptoms and cognitive deficits were modeled in different cortical areas by the dopaminergic agonist (amphetamine) and the N-methyl-D-aspartate (NMDA) receptor antagonists (PCP and MK801)...
December 18, 2017: Translational Psychiatry
Saher Zaidi, Jason Gandhi, Sohrab Vatsia, Noel L Smith, Sardar Ali Khan
Congenital central hypoventilation syndrome (CCHS), known colloquially as Ondine's curse, is a rare disorder characterized by impaired autonomic control of breathing during sleep from the loss of vagal input and diminished sensitivity of CO2 receptors in the medulla. CCHS correlates to the malformation of the neural crest located in the brainstem; this consequently affects the loss of sensitivity of CO2 chemoreceptors, bringing about hypoventilation during sleep. The primary cause of CCHS is the mutation of the paired-like homeobox PHO2XB gene, found in 90% of the patients...
November 13, 2017: Autonomic Neuroscience: Basic & Clinical
Christina M Estrada, Valentina Ghisays, Elizabeth T Nguyen, Jody L Caldwell, Joshua Streicher, Matia B Solomon
Declining estradiol (E2), as occurs during menopause, increases risk for obesity and psychopathology (i.e., depression, anxiety). E2 modulates mood and energy homeostasis via binding to estrogen receptors (ER) in the brain. The often comorbid and bidirectional relationship between mood and metabolic disorders suggests shared hormonal and/or brain networks. The medial amygdala (MeA) is abundant in ERs and regulates mood, endocrine, and metabolic stress responses; therefore we tested the hypothesis that E2 in the MeA mitigates emotional and metabolic dysfunction in a rodent model of surgical menopause...
December 14, 2017: Hormones and Behavior
María Pascual, Jorge Montesinos, Consuelo Guerri
Adolescence is a critical stage of brain maturation in which important plastic and dynamic processes take place in different brain regions, leading to development of the adult brain. Ethanol drinking in adolescence disrupts brain plasticity and causes structural and functional changes in immature brain areas (prefrontal cortex, limbic system) that result in cognitive and behavioral deficits. These changes, along with secretion of sexual and stress-related hormones in adolescence, may impact self-control, decision making, and risk-taking behaviors that contribute to anxiety and initiation of alcohol consumption...
December 7, 2017: Journal of Neuroscience Research
Donna L Korol, Wei Wang
Understanding the organizing and activating effects of gonadal steroids on adult physiology can guide insight into sex differences in and hormonal influences on health and disease, ranging from diabetes and other metabolic disorders, emotion and stress regulation, substance abuse, pain perception, immune function and inflammation, to cognitive function and dysfunction accompanying neurological disorders. Because the brain is highly sensitive to many forms of estrogens, it is not surprising that many adult behaviors, including cognitive function, are modulated by estrogens...
December 5, 2017: Physiology & Behavior
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