دانلود مقاله ISI انگلیسی شماره 30182
عنوان فارسی مقاله

کاهش بویایی و بروز گیرنده طعم در قشر جلو مغزی خلفی جانبی در اسکیزوفرنی مزمن

کد مقاله سال انتشار مقاله انگلیسی ترجمه فارسی تعداد کلمات
30182 2015 صفحه PDF سفارش دهید محاسبه نشده
خرید مقاله
پس از پرداخت، فوراً می توانید مقاله را دانلود فرمایید.
عنوان انگلیسی
Decrease in olfactory and taste receptor expression in the dorsolateral prefrontal cortex in chronic schizophrenia
منبع

Publisher : Elsevier - Science Direct (الزویر - ساینس دایرکت)

Journal : Journal of Psychiatric Research, Volume 60, January 2015, Pages 109–116

کلمات کلیدی
اسکیزوفرنی - قشر جلو مغزی - گیرنده های بویایی - گیرنده طعم - داروهای ضد روان پریشی -
پیش نمایش مقاله
پیش نمایش مقاله کاهش بویایی و بروز گیرنده طعم در قشر جلو مغزی خلفی جانبی در اسکیزوفرنی مزمن

چکیده انگلیسی

We have recently identified up- or down-regulation of the olfactory (OR) and taste (TASR) chemoreceptors in the human cortex in several neurodegenerative diseases, raising the possibility of a general deregulation of these genes in neuropsychiatric disorders. In this study, we explore the possible deregulation of OR and TASR gene expression in the dorsolateral prefrontal cortex in schizophrenia. We used quantitative polymerase chain reaction on extracts from postmortem dorsolateral prefrontal cortex of subjects with chronic schizophrenia (n = 15) compared to control individuals (n = 14). Negative symptoms were evaluated premortem by the Positive and Negative Syndrome and the Clinical Global Impression Schizophrenia Scales. We report that ORs and TASRs are deregulated in the dorsolateral prefrontal cortex in schizophrenia. Seven out of eleven ORs and four out of six TASRs were down-regulated in schizophrenia, the most prominent changes of which were found in genes from the 11p15.4 locus. The expression did not associate with negative symptom clinical scores or the duration of the illness. However, most ORs and all TASRs inversely associated with the daily chlorpromazine dose. This study identifies for the first time a decrease in brain ORs and TASRs in schizophrenia, a neuropsychiatric disease not linked to abnormal protein aggregates, suggesting that the deregulation of these receptors is associated with altered cognition of these disorders. In addition, the influence of antipsychotics on the expression of ORs and TASRs in schizophrenia suggests that these receptors could be involved in the mechanism of action or side effects of antipsychotics.

مقدمه انگلیسی

Ectopic expression of olfactory and taste receptors (ORs and TASRs, respectively) has been described in several organs and tissues (Behrens and Meyerhof, 2010, Branscomb et al., 2000, De la Cruz et al., 2009, Feldmesser et al., 2006, Li, 2013, Parmentier et al., 1992, Vanderhaeghen et al., 1997, Xu et al., 2013, Yamamoto and Ishimaru, 2013 and Zhang et al., 2007). Their function in these locations is not known in most cases but it has been proposed that both ORs and TASRs play particular roles in autocrine, paracrine and endocrine signaling (Aggio et al., 2012, Deshpande et al., 2010, Dreyer, 1998, Fukuda et al., 2004, Griffin et al., 2009, Kang and Koo, 2012, Kinnamon, 2012, Spehr et al., 2003 and Spehr et al., 2004). A variety of compounds, mostly of unknown origin and function, can bind to autocrine receptors on the same cell, neighboring cells or distant cells. More recently, ORs and TASRs, and their down-stream effectors have been identified in the rodent and human brain (Dehkordi et al., 2012, Garcia-Esparcia et al., 2013, Grison et al., 2014, Otaki et al., 2004 and Singh et al., 2011), with a widespread distribution although with regional variations (Garcia-Esparcia et al., 2013). Moreover, ORs are functional—at least those expressed in dopaminergic cultured cells—in the presence of selective odorant molecules (Grison et al., 2014). About 400 ORs and dozens of TASRs are putatively expressed in the brain and ganglia of the autonomic nervous system (Glusman et al., 2001, Malnic et al., 2004, Niimura and Nei, 2005, Zhang et al., 2007 and Zozulya et al., 2001), suggesting that they have substantial brain functions in physiological conditions (Barnea et al., 2004, Feinstein et al., 2004, Feinstein and Mombaerts, 2004, Otaki et al., 2004 and Weber et al., 2002). Interestingly, ORs and TASRs are deregulated, at least in the frontal cortex and substantia nigra, in Parkinson's disease, the frontal cortex and entorhinal cortex in Alzheimer's disease and progressive supranuclear palsy, and the frontal cortex and cerebellum in Creutzfeldt-Jakob disease ( Ansoleaga et al., 2013 and Garcia-Esparcia et al., 2013). Deregulation is not merely result of neuron loss characteristic of these neurodegenerative diseases, as some ORs and TASRs are down-regulated or up-regulated in a disease-specific manner ( Ansoleaga et al., 2013 and Garcia-Esparcia et al., 2013). Moreover, deregulation of ORs has also been found in APP/PS1 transgenic mice bearing the Swedish APP mutation and PS1 deletion, which are used as a model for Alzheimer's disease ( Ansoleaga et al., 2013). Although all these diseases have disorders in olfaction, mainly characterized by the loss of sense of smell, and in some of them the loss of taste to bitter substances (even that taste is rarely examined in neurodegenerative diseases), the mechanisms leading to loss of olfaction and taste have been attributed to the presence of abnormal protein deposits in the olfactory epithelium, olfactory bulb and tract, and to the abnormal innervation of primary and secondary olfactory and taste centers ( Attems et al., 2014, Doty, 2003 and Doty, 2012). Schizophrenia (SZ) is a severe mental disorder affecting around 0.5–1% of the world adult population (Tandon et al., 2008). This disease constitutes a complex disorder with great variability in the manifestation of positive, negative and cognitive symptoms. Negative symptoms (i.e. lack of volition, poor or absent social functioning, blunted affect) and cognitive impairments (i.e. deficits in executive functions and working memory) are the core symptoms of schizophrenia and are the most persistent manifestations of the disease (Gold, 2004, Stahl and Buckley, 2007 and Tandon et al., 2009). The dorsolateral prefrontal cortex (DLPFC) is involved these cognitive deficits (Frith and Dolan, 1996, Lewis and Moghaddam, 2006 and Teffer and Semendeferi, 2012) and negative symptoms (Semkovska et al., 2001 and Toda and Abi-Dargham, 2007). A dysfunction in this region has been widely described in functional and structural imaging studies and in many molecular reports (English et al., 2011, Goldstein et al., 1999, Konradi, 2005 and Wong and Van Tol, 2003). Altered olfactory functions have been reported in schizophrenia and their origin has been associated with altered secondary olfactory centers and also linked to altered olfactory bulb volume (Auster et al., 2014, Cohen et al., 2012, Kayser et al., 2013, Moberg et al., 2006, Nguyen et al., 2011, Nguyen et al., 2010, Rupp, 2010 and Schneider et al., 2007). Hypoactivity and hypometabolism in frontal regions has been reported in SZ patients with olfactory agnosia (inability to recognize odors) or during olfactory identification, supporting a role of the frontal lobe in olfactory dysfunction in schizophrenia (Clark et al., 1991 and Malaspina et al., 1998). The most severe and consistent dysfunctions reported in SZ patients were impaired odor identification and discrimination, implicating prefrontal neural compromise, while milder deficits of olfactory acuity or sensitivity, also reported in SZ, reflects a peripheral impairment of the olfactory system (Brewer and Pantelis, 2010, Cohen et al., 2012, Moberg et al., 1999 and Rupp, 2010). In fact, electrical depolarization of the olfactory receptor neurons following stimulation with different doses and durations of hydrogen sulfide, a pure olfactory nerve stimulant, resulted in altered electric patterns, also supporting a primary olfactory receptor neuron dysfunction in schizophrenia (Turetsky et al., 2009). Regarding taste perception, there is no general agreement about the nature of taste disorders in schizophrenia, at least regarding the inability to taste the bitter chemical phenylthiocarbamide (Compton et al., 2007, Compton et al., 2013, Moberg et al., 2012 and Moberg et al., 2007). Nothing is known about the expression of ORs and TASRs in the brains of patients suffering from schizophrenia. For this reason, the present study was designed to gain information about possible deregulation of OR and TASR expression in the dorsolateral prefrontal cortex in schizophrenia.

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