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Neuromolecular Medicine

Abdolkarim Hosseini, Homayoun Khazali
It is an established fact that orexin plays an important role in regulating the reproductive axis and the secretions of gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH). However, its precise cellular and molecular mechanisms are not fully recognized. Accordingly, the aim of the present study is to find out whether the central injection of orexin A (OXA) and its antagonists, SB-334867 (as orexin receptor antagonist 1; OX1RA) and JNJ-10397049 (as orexin receptor antagonist 2; OX2RA), either alone or in combination, can leave any impact on the reproductive axis (either hormonal or behavioral) in the male Wistar rats...
September 14, 2018: Neuromolecular Medicine
Yueqing Gong, Kun Wang, Sheng-Ping Xiao, Panying Mi, Wanjie Li, Yu Shang, Fei Dou
Human tetratricopeptide repeat domain 3 (TTC3) is a gene on 21q22.2 within the Down syndrome critical region (DSCR). Earlier studies suggest that TTC3 may be an important regulator in individual development, especially in neural development. As an E3 ligase, TTC3 binds to phosphorylated Akt and silence its activity via proteasomal cascade. Several groups also reported the involvement of TTC3 in familial Alzheimer's disease recently. In addition, our previous work shows that TTC3 also regulates the degradation of DNA polymerase gamma and over-expressed TTC3 protein tends to form insoluble aggregates in cells...
September 10, 2018: Neuromolecular Medicine
Wanli Yu, Sai Liang, Chunzhi Zhang
GBM is the highest incidence in primary intracranial malignancy, and it remains poor prognosis even though the patient is gave standard treatment. Despite decades of intense research, the complex biology of GBM remains elusive. In view of eight hallmarks of cancer which were proposed in 2011, studies related to the eight biological capabilities in GBM have made great progress. From these studies, it can be inferred that miRs, as a mode of post-transcriptional regulation, are involved in regulating these malignant biological hallmarks of GBM...
September 4, 2018: Neuromolecular Medicine
Liya Sun, Lei Xia, Mingtai Wang, Dengna Zhu, Yangong Wang, Dan Bi, Juan Song, Caiyun Ma, Chao Gao, Xiaoli Zhang, Yanyan Sun, Xiaoyang Wang, Changlian Zhu, Qinghe Xing
Cerebral palsy (CP) is a leading cause of neurological disability among young children. Congenial and adverse perinatal clinical conditions, such as genetic factors, perinatal infection, and asphyxia, are risk factors for CP. Oligodendrocyte transcription factor (OLIG2) is a protein that is expressed in brain oligodendrocyte cells and is involved in neuron repair after brain injury. In this study, we employed a Chinese Han cohort of 763 CP infants and 738 healthy controls to study the association of OLIG2 gene polymorphisms with CP...
September 3, 2018: Neuromolecular Medicine
D Khatri, D Zizioli, A Trivedi, G Borsani, E Monti, D Finazzi
Pantothenate Kinase-Associated Neurodegeneration (PKAN) is a genetic and early-onset neurodegenerative disorder characterized by iron accumulation in the basal ganglia. It is due to mutations in Pantothenate Kinase 2 (PANK2), an enzyme that catalyzes the phosphorylation of vitamin B5, first and essential step in coenzyme A (CoA) biosynthesis. Most likely, an unbalance of the neuronal levels of this important cofactor represents the initial trigger of the neurodegenerative process, yet a complete understanding of the connection between PANK2 malfunctioning and neuronal death is lacking...
August 23, 2018: Neuromolecular Medicine
Mohit Kumar, Rajat Sandhir
Homocysteine (Hcy) is a sulfur-containing amino acid derived from methionine metabolism. Elevated plasma Hcy levels (> 15 µM) result in a condition called hyperhomocysteinemia (HHcy), which is an independent risk factor in the development of various neurodegenerative disorders. Reactive oxygen species (ROS) produced by auto-oxidation of Hcy have been implicated in HHcy-associated neurological conditions. Hydrogen sulfide (H2 S) is emerging as a potent neuroprotective and neuromodulator molecule. The present study was aimed to evaluate the ability of NaHS (a source of H2 S) to attenuate Hcy-induced oxidative stress and altered antioxidant status in animals subjected to HHcy...
August 13, 2018: Neuromolecular Medicine
Weam Fageera, Sarojini M Sengupta, Aurelie Labbe, Natalie Grizenko, Ridha Joober
Results of candidate gene investigations in ADHD have been difficult to replicate. The complexity of the phenotypes and their underlying determinants, and the relatively small effect sizes of genetic variants may, in part, be contributing to these inconsistencies. The objective of this study is to conduct an exploratory analysis using a comprehensive approach to investigate the role of candidate genes. This approach combines a dimensional behavioural approach akin to Research Domain Criteria (RDoC), a pharmaco-dynamic evaluation of behaviours relevant to ADHD, together with association and linkage testing in a large sample of children with ADHD...
July 26, 2018: Neuromolecular Medicine
Shubhrajit Roy, Prosenjit Pal, Sampurna Ghosh, Sreyashi Bhattacharya, Shyamal Kumar Das, Prasanta Kumar Gangopadhyay, Ashish Bavdekar, Kunal Ray, Mainak Sengupta, Jharna Ray
Wilson's disease (WD), an inborn error of copper metabolism caused by mutations in the ATPase copper transporting beta (ATP7B) gene, manifests variable age of onset and different degrees of hepatic and neurological disturbances. This complex phenotypical outcome of a classical monogenic disease can possibly be explained by modifier loci regulating the clinical course of the disease. The brain-derived neurotropic factor (BDNF), critical for the survival, morphogenesis, and plasticity of the neurons, and the dopamine receptor D2 (DRD2), one of the most abundant dopamine receptors in the brain, have been highlighted in the pathophysiology of various neuropsychiatric diseases...
July 10, 2018: Neuromolecular Medicine
Menizibeya O Welcome, Nikos E Mastorakis
The astrocyte-neuron lactate shunt (ANLS) hypothesis is the most widely accepted model of brain glucose metabolism. However, over the past decades, research has shown that neuronal and astrocyte plasma membrane receptors, in particular, GLUT2, Kir6.2 subunit of the potassium ATP-channel, SGLT-3 acting as glucosensors, play a pivotal role in brain glucose metabolism. Although both ANLS hypothesis and glucosensor model substantially improved our understanding of brain glucose metabolism, the latter appears to be gaining more attention in the scientific community as the former could not account for new research data indicating that hypothalamic and brainstem neurons may not require astrocyte-derived lactate for energy...
September 2018: Neuromolecular Medicine
Léo Mietton, Nicolas Lebrun, Irina Giurgea, Alice Goldenberg, Benjamin Saintpierre, Juliette Hamroune, Alexandra Afenjar, Pierre Billuart, Thierry Bienvenu
A growing number of histone modifiers are involved in human neurodevelopmental disorders, suggesting that proper regulation of chromatin state is essential for the development of the central nervous system. Among them, heterozygous de novo variants in KMT2A, a gene coding for histone methyltransferase, have been associated with Wiedemann-Steiner syndrome (WSS), a rare developmental disorder mainly characterized by intellectual disability (ID) and hypertrichosis. As KMT2A is known to regulate the expression of multiple target genes through methylation of lysine 4 of histone 3 (H3K4me), we sought to investigate the transcriptomic consequences of KMT2A variants involved in WSS...
September 2018: Neuromolecular Medicine
Hossein Sanjari Moghaddam, Zahra Valitabar, Amir Ashraf-Ganjouei, Mahtab Mojtahed Zadeh, Farzaneh Ghazi Sherbaf, Mohammad Hadi Aarabi
Parkinson' disease (PD) is characterized by motor symptoms including bradykinesia, resting tremor, postural instability, and rigidity and non-motor symptoms such as cognitive impairment, sleep disorder, and depression. Neuroinflammation has been recently implicated in pathophysiology of both motor and non-motor symptoms of PD. One of the most notable inflammatory proteins is C-reactive protein (CRP), which is elevated in the conditions of systemic inflammation. Using BioFIND database, we scrutinized the possible association between cerebrospinal fluid (CSF) levels of CRP and severity of PD motor and non-motor symptoms...
September 2018: Neuromolecular Medicine
Muaz Belviranlı, Nilsel Okudan
This study aimed to determine the effect of exercise training on cognitive functioning, and hippocampal PGC-1α, FNDC5, BDNF, and other cognition-related gene and protein expression in rats. Rats were divided into 4 groups based on age [3 months (young) vs. 20 months (aged)] and training status (control vs. exercise training). The rats that exercised voluntarily performed exercise training for 90 days, and then all the rats underwent several methods of behavioral assessment. Locomotor activity and spatial memory were lower but anxiety scores were higher in the aged control rats, than in the young control, young exercised, and aged exercised rats (P < 0...
September 2018: Neuromolecular Medicine
Duygu Gezen-Ak, İrem L Atasoy, Esin Candaş, Merve Alaylıoğlu, Erdinç Dursun
Our previous study demonstrated the translocation of Aβ1-42 to the nucleus in response to antibiotic treatment, and interpreted it as a possible transcriptional response of Aβ1-42 to antibiotics. The present study aims to investigate how amyloid acts on the key elements of neurodegeneration and the molecules involved in the induction of Aβ1-42 production. For this purpose, we investigated the acute effect of Aβ1-42 on the transcriptional levels of genes that have roles in the mechanisms that produce Aβ itself: alpha secretase (ADAM10), beta secretase (BACE1), the gamma secretase complex (PS-1, PS-2, Nicastrin), the substrate APP, APOE (the significant risk factor for sporadic form of the AD), TREM2 (recently indicated as a contributor to AD risk), NMDAR subunits and PKCzeta (contributors of memory and learning), and key elements of tau pathology such as tau, GSK3α, GSK3β, and Cdk5...
September 2018: Neuromolecular Medicine
María Belén Ruiz-Roso, Elena Olivares-Álvaro, José Carlos Quintela, Sandra Ballesteros, Juan F Espinosa-Parrilla, Baltasar Ruiz-Roso, Vicente Lahera, Natalia de Las Heras, Beatriz Martín-Fernández
Docosahexaenoic acid (DHA, 22:6 n-3) is an essential omega-3 (ω-3) long chain polyunsaturated fatty acid of neuronal membranes involved in normal growth, development, and function. DHA has been proposed to reduce deleterious effects in neurodegenerative processes. Even though, some inconsistencies in findings from clinical and pre-clinical studies with DHA could be attributed to the presence of phytanic acid (PhA) in standard DHA treatments. Thus, the aim of our study was to analyze and compare the effects of a low PhA-concentrated DHA with a standard PhA-concentrated DHA under different neurotoxic conditions in BV-2 activated microglial cells...
September 2018: Neuromolecular Medicine
Muskan Gupta, Gurcharan Kaur
Reactive gliosis, microgliosis, and subsequent secretion of various inflammatory mediators like cytokines, proteases, reactive oxygen, and nitrogen species are the suggested key players associated with systemic inflammation-driven neuroinflammation and cognitive impairments in various neurological disorders. Conventionally, non-steroidal anti-inflammatory drugs are prescribed to suppress inflammation but due to their adverse effects, their usage is not well accepted. Natural products are emerging better therapeutic agents due to their affordability and inherent pleiotropic biological activities...
September 2018: Neuromolecular Medicine
Sun Mi Gu, Hee Pom Lee, Young Wan Ham, Dong Ju Son, Hoi Yeong Kim, Ki Wan Oh, Sang-Bae Han, Jaesuk Yun, Jin Tae Hong
Amyloidogenesis is known to cause Alzheimer's disease. Our previous studies have found that lipopolysaccharide (LPS) causes neuroinflammation and amyloidogenesis through activation of nuclear factor kappaB (NF-κB). Piperlongumine (PL) is an alkaloid amide found naturally in long pepper (Piper longum) isolates; it was reported to have inhibitory effects on NF-κB activity. We therefore investigated whether PL exhibits anti-inflammatory and anti-amyloidogenic effects by inhibiting NF-κB. A murine model of LPS-induced memory impairment was made via the intraperitoneal (i...
September 2018: Neuromolecular Medicine
Lian Gu, Jingyan Huang, Jinhong Li, Siyun Huang, Minhua Li, Lin Gong, Tongshun Li, Li Su
A quantitative transcriptomics analysis has reported that Calmodulin 1 (CALM1) is highly expressed in human brain tissues. This study aims to evaluate the relationship between CALM1 rs3179089 polymorphism and ischemic stroke (IS) in Chinese Han population. A total of 550 patients with IS and 550 control subjects were recruited and genotyped using Sequenom MassArray technology. The mRNA expression of CALM1 was measured using quantitative real-time polymerase chain reaction. CALM1 mRNA expression was significantly higher in patients with IS than that in control subjects (P = 0...
June 2018: Neuromolecular Medicine
Le Wei, Li-Yuan Kan, Hai-Ying Zeng, Yi-Yun Tang, Hong-Lin Huang, Ming Xie, Wei Zou, Chun-Yan Wang, Ping Zhang, Xiao-Qing Tang
Our previous works have shown that hydrogen sulfide (H2 S) significantly attenuates chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors and hippocampal endoplasmic reticulum (ER) stress. Brain-derived neurotrophic factor (BDNF) generates an antidepressant-like effect by its receptor tyrosine protein kinase B (TrkB). We have previously found that H2 S upregulates the expressions of BDNF and p-TrkB in the hippocampus of CUMS-exposed rats. Therefore, the present work was to explore whether BDNF/TrkB pathway mediates the antidepressant-like role of H2 S by blocking hippocampal ER stress...
June 2018: Neuromolecular Medicine
Jong-Suep Baek, Jie Kai Tee, Yi Yun Pang, Ern Yu Tan, Kah Leong Lim, Han Kiat Ho, Say Chye Joachim Loo
Oral administration of levodopa (LD) is the gold standard in managing Parkinson's disease (PD). Although LD is the most effective drug in treating PD, chronic administration of LD induces levodopa-induced dyskinesia. A continuous and sustained provision of LD to the brain could, therefore, reduce peak-dose dyskinesia. In commercial oral formulations, LD is co-administrated with an AADC inhibitor (carbidopa) and a COMT inhibitor (entacapone) to enhance its bioavailability. Nevertheless, patients are known to take up to five tablets a day because of poor sustained-releasing capabilities that lead to fluctuations in plasma concentrations...
June 2018: Neuromolecular Medicine
Paulo José Lorenzoni, Rosana Herminia Scola, Claudia Suemi Kamoi Kay, Lineu Cesar Werneck, Rita Horvath, Hanns Lochmüller
Congenital myasthenic syndromes (CMS) are heterogeneous genetic diseases in which neuromuscular transmission is compromised. CMS resembling the Lambert-Eaton myasthenic syndrome (CMS-LEMS) are emerging as a rare group of distinct presynaptic CMS that share the same electrophysiological features. They have low compound muscular action potential amplitude that increment after brief exercise (facilitation) or high-frequency repetitive nerve stimulation. Although clinical signs similar to LEMS can be present, the main hallmark is the electrophysiological findings, which are identical to autoimmune LEMS...
June 2018: Neuromolecular Medicine
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