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Molecular Neurobiology

Alexander Jack, Mohammad I K Hamad, Steffen Gonda, Sebastian Gralla, Steffen Pahl, Michael Hollmann, Petra Wahle
During neuronal development, AMPA receptors (AMPARs) and NMDA receptors (NMDARs) are important for neuronal differentiation. Kainate receptors (KARs) are closely related to AMPARs and involved in the regulation of cortical network activity. However, their role for neurite growth and differentiation of cortical neurons is unclear. Here, we used KAR agonists and overexpression of selected KAR subunits and their auxiliary neuropilin and tolloid-like proteins, NETOs, to investigate their influence on dendritic growth and network activity in organotypic cultures of rat visual cortex...
November 12, 2018: Molecular Neurobiology
Fernanda Silva Rodrigues, Viviane Nogueira de Zorzi, Marla Parizzi Funghetto, Fernanda Haupental, Alexandra Seide Cardoso, Sara Marchesan, Andréia M Cardoso, Maria Rosa C Schinger, Alencar Kolinski Machado, Ivana Beatrice Mânica da Cruz, Marta Maria Medeiros Frescura Duarte, Léder L Xavier, Ana Flavia Furian, Mauro Schneider Oliveira, Adair Roberto Soares Santos, Luiz Fernando Freire Royes, Michele Rechia Fighera
Dysfunction of basal ganglia neurons is a characteristic of glutaric acidemia type I (GA-I), an autosomal recessive inherited neurometabolic disease characterized by deficiency of glutaryl-CoA dehydrogenase (GCDH) and accumulation of glutaric acid (GA). The affected patients present clinical manifestations such as motor dysfunction and memory impairment followed by extensive striatal neurodegeneration. Knowing that there is relevant striatal dysfunction in GA-I, the purpose of the present study was to verify the performance of young rats chronically injected with GA in working and procedural memory test, and whether N-acetylcysteine (NAC) would protect against impairment induced by GA...
November 12, 2018: Molecular Neurobiology
Md Sahab Uddin, Abdullah Al Mamun, Md Tanvir Kabir, Md Jakaria, Bijo Mathew, George E Barreto, Ghulam Md Ashraf
Medicinal plants are the backbone of modern medicine. In recent times, there is a great urge to discover nootropic medicinal plants to reverse cognitive dysfunction owing to their less adverse effects. Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by the inevitable loss of cognitive function, memory and language impairment, and behavioral disturbances, which turn into gradually more severe. Alzheimer's has no current cure, but symptomatic treatments are available and research continues...
November 9, 2018: Molecular Neurobiology
Lucas Porcello Schilling, Tharick A Pascoal, Eduardo R Zimmer, Sulantha Mathotaarachchi, Monica Shin, Carlos Roberto de Mello Rieder, Serge Gauthier, André Palmini, Pedro Rosa-Neto
We investigated the association between amyloid-β deposition and white matter (WM) integrity as a determinant of brain glucose hypometabolism across the Alzheimer's disease (AD) spectrum. We assessed ninety-six subjects (27 cognitively normal, 49 mild cognitive impairment, and 20 AD dementia) who underwent [18 F]FDG and [18 F]Florbetapir positron emission tomography (PET) as well as magnetic resonance imaging (MRI) with diffusion tensor imaging. Among the regions with reduced fractional anisotropy (FA) in the AD group, we selected a voxel of interest in the angular bundle bilaterally for subsequent analyses...
November 9, 2018: Molecular Neurobiology
Sherice Williams, Mohammed Hossain, Saurabh Mishra, Jorge Gonzalez-Martinez, Imad Najm, Chaitali Ghosh
Death-associated protein kinase (DAPK) is a key player in various cell death signaling pathways. Prolonged seizures induce neuronal stress; thus, we studied DAPK expression in resected brain tissues from patients with refractory epilepsy and the pathophysiological relevance of neurovascular DAPK. We used brain resections from temporal lobe epilepsy (TLE), tumor (BT), arteriovenous malformation (AVM), and autopsy, and isolated human endothelial cells (EPI-ECs) and glial cells (EPI-Astro) from epileptic brains compared to control brain endothelial cells (HBMECs) and astrocytes...
November 9, 2018: Molecular Neurobiology
Inja Cho, Kyoung Hoon Jeong, Jing Zhu, Yun Ho Choi, Kyoo Ho Cho, Kyoung Heo, Won-Joo Kim
In pathological conditions such as status epilepticus (SE), neuronal cell death can occur due to oxidative stress that is caused by an excessive production and accumulation of reactive oxygen species (ROS). Sirtuin3 (Sirt3) plays an important role in maintaining appropriate ROS levels by regulating manganese superoxide dismutase (MnSOD), which scavenges ROS in mitochondria. Using a SE model, we demonstrated that Sirt3 directly regulated MnSOD activity by deacetylation, which protects hippocampal cells against damage from ROS...
November 8, 2018: Molecular Neurobiology
Abigail Weiland, Yamei Wang, Weihua Wu, Xi Lan, Xiaoning Han, Qian Li, Jian Wang
Ferroptosis is a recently identified, iron-regulated, non-apoptotic form of cell death. It is characterized by cellular accumulation of lipid reactive oxygen species that ultimately leads to oxidative stress and cell death. Although first identified in cancer cells, ferroptosis has been shown to have significant implications in several neurologic diseases, such as ischemic and hemorrhagic stroke, Alzheimer's disease, and Parkinson's disease. This review summarizes current research on ferroptosis, its underlying mechanisms, and its role in the progression of different neurologic diseases...
November 8, 2018: Molecular Neurobiology
Marcelina Firkowska, Matylda Macias, Jacek Jaworski
The proper shape of dendritic arbors of different types of neurons determines their proper communication within neuronal networks. The shape of dendritic arbors is acquired during a complex and multistep process called dendritogenesis. In most cases, once proper morphology is achieved, it remains stable throughout the lifespan, with the exception of rare events during which dendrites are abruptly pruned. The endosomal sorting complex required for transport (ESCRT) is multisubunit machinery that is involved in various cellular processes when membrane scission is needed...
November 7, 2018: Molecular Neurobiology
Ming Chen, Lin-Lin Bi
The dysregulation of fear learning and abnormal activities of cerebral networks may contribute to the etiologies of anxiety disorders. Although it has been proposed that decreased activity in the paraventricular nucleus of the thalamus (PVT) to the lateral central nucleus of amygdala (CeL) pathway could induce an attenuation of learned fear, no study has shown the effect of the direct optogenetic activation of PVT projecting CeL neurons in vivo on unconditioned fear-related behaviors or learned fear expression...
November 7, 2018: Molecular Neurobiology
Anna Gandaglia, Elena Brivio, Sara Carli, Michela Palmieri, Francesco Bedogni, Gilda Stefanelli, Anna Bergo, Barbara Leva, Chiara Cattaneo, Lara Pizzamiglio, Marco Cicerone, Veronica Bianchi, Charlotte Kilstrup-Nielsen, Ilda D'Annessa, Daniele Di Marino, Patrizia D'Adamo, Flavia Antonucci, Angelisa Frasca, Nicoletta Landsberger
MeCP2 is a fundamental protein associated with several neurological disorders, including Rett syndrome. It is considered a multifunctional factor with a prominent role in regulating chromatin structure; however, a full comprehension of the consequences of its deficiency is still lacking. Here, we characterize a novel mouse model of Mecp2 bearing the human mutation Y120D, which is localized in the methyl-binding domain. As most models of Mecp2, the Mecp2Y120D mouse develops a severe Rett-like phenotype. This mutation alters the interaction of the protein with chromatin, but surprisingly, it also impairs its association with corepressors independently on the involved interacting domains...
November 6, 2018: Molecular Neurobiology
Agnieszka Wnuk, Joanna Rzemieniec, Jakub Staroń, Ewa Litwa, Władysław Lasoń, Andrzej Bojarski, Małgorzata Kajta
The UV absorber benzophenone-3 (BP-3) is the most extensively used chemical substance in various personal care products. Despite that BP-3 exposure is widespread, knowledge about the impact of BP-3 on the brain development is negligible. The present study aimed to explore the mechanisms of prenatal exposure to BP-3 in neuronal cells, with particular emphasis on autophagy and nuclear receptors signaling as well as the epigenetic and post-translational modifications occurring in response to BP-3. To observe the impact of prenatal exposure to BP-3, we administered BP-3 to pregnant mice, and next, we isolated brain tissue from pretreated embryos for primary cell neocortical culture...
November 6, 2018: Molecular Neurobiology
Tomoyuki Nishizaki
Amyloid β (Aβ) peptide is a critical causative factor in Alzheimer's disease (AD) and of a variety of fragmented Aβ peptides Aβ1-42 thought to exhibit the most neurotoxic effect. The present study investigated the effects of Fe3+ on Aβ1-42 internalization and Aβ1-42 -induced caspase activation and neurotoxicity using mouse hippocampal slices and cultured PC-12 cells. Extracellularly applied Aβ1-42 increased the cell-associated Aβ1-42 levels in a concentration-dependent manner, and the effect was enhanced by adding Fe3+ ...
November 6, 2018: Molecular Neurobiology
Khosro Jamebozorgi, Eskandar Taghizadeh, Daryoush Rostami, Hosein Pormasoumi, George E Barreto, Seyed Mohammad Gheibi Hayat, Amirhossein Sahebkar
Parkinson's disease is a neurodegenerative disorder accompanied by depletion of dopamine and loss of dopaminergic neurons in the brain that is believed to be responsible for the motor and non-motor symptoms in this disease. The main drug prescribed for Parkinsonian patients is L-dopa, which can be converted to dopamine by passing through the blood-brain barrier. Although L-dopa is able to improve motor function and improve the quality of life in the patients, there is inter-individual variability and some patients do not achieve the therapeutic effect...
November 5, 2018: Molecular Neurobiology
Manjari Kiran, Ajay Chatrath, Xiwei Tang, Daniel Macrae Keenan, Anindya Dutta
Diffuse low-grade and intermediate-grade gliomas (together known as lower grade gliomas, WHO grade II and III) develop in the supporting glial cells of brain and are the most common types of primary brain tumor. Despite a better prognosis for lower grade gliomas, 70% of patients undergo high-grade transformation within 10 years, stressing the importance of better prognosis. Long non-coding RNAs (lncRNAs) are gaining attention as potential biomarkers for cancer diagnosis and prognosis. We have developed a computational model, UVA8, for prognosis of lower grade gliomas by combining lncRNA expression, Cox regression, and L1-LASSO penalization...
November 3, 2018: Molecular Neurobiology
Marta Sánchez-Soto, Hideaki Yano, Ning-Sheng Cai, Verònica Casadó-Anguera, Estefanía Moreno, Vicent Casadó, Sergi Ferré
The two most common polymorphisms of the human DRD4 gene encode a dopamine D4 receptor (D4R) with four or seven repeats of a proline-rich sequence of 16 amino acids (D4.4R or D4.7R). Although the seven-repeat polymorphism has been repeatedly associated with attention-deficit hyperactivity disorder and substance use disorders, the differential functional properties between D4.4R and D4.7R remained enigmatic until recent electrophysiological and optogenetic-microdialysis experiments indicated a gain of function of D4...
November 1, 2018: Molecular Neurobiology
Facundo H Prado Spalm, Marcela S Vera, Marcos J Dibo, M Victoria Simón, Luis E Politi, Nora P Rotstein
Ceramide (Cer) has a key role inducing cell death and has been proposed as a messenger in photoreceptor cell death in the retina. Here, we explored the pathways induced by C2 -acetylsphingosine (C2 -Cer), a cell-permeable Cer, to elicit photoreceptor death. Treating pure retina neuronal cultures with 10 μM C2 -Cer for 6 h selectively induced photoreceptor death, decreasing mitochondrial membrane potential and increasing the formation of reactive oxygen species (ROS). In contrast, amacrine neurons preserved their viability...
November 1, 2018: Molecular Neurobiology
Theodore D Cosco, Toby Pillinger, Hadeer Emam, Marco Solmi, Sanjay Budhdeo, A Matthew Prina, Michael Maes, Dan J Stein, Brendon Stubbs, Andre F Carvalho
Some lines of evidence have indicated that immune dysregulation could play a role in the pathophysiology of obsessive-compulsive disorder (OCD). However, results have been inconsistent across studies. Thus, a systematic review and meta-analysis of studies measuring immune mediators in participants with OCD compared to healthy controls (HC) was conducted. The PubMed/MEDLINE, PsycINFO, and EMBASE electronic databases were systematically searched from inception through June 21, 2018. Sixteen studies met inclusion criteria comprising data from 1001 participants (538 with OCD and 463 were HCs)...
October 31, 2018: Molecular Neurobiology
Chia Jie Tan, Sheree Wan Ting Lim, Yi Long Toh, Terence Ng, Angie Yeo, Maung Shwe, Koon Mian Foo, Pat Chu, Amit Jain, Si-Lin Koo, Rebecca A Dent, Raymond Chee Hui Ng, Yoon Sim Yap, Elaine H Lim, Kiley Wei-Jen Loh, Wen Yee Chay, Guek Eng Lee, Tira Jing Ying Tan, Sok Yuen Beh, Mabel Wong, Jack Junjie Chan, Chiea Chuen Khor, Han Kiat Ho, Alexandre Chan
Cancer-related cognitive impairment (CRCI) adversely affects cancer patients. We had previously demonstrated that the BDNF Val66Met genetic polymorphism is associated with lower odds of subjective CRCI in the multitasking and verbal ability domains among breast cancer patients receiving chemotherapy. To further assess our previous findings, we evaluated the association of BDNF Val66Met polymorphism with subjective and objective CRCI in a temporally separate cohort of patients and pooled findings from both the original (n = 145) and current (n = 193) cohorts in a meta-analysis...
October 31, 2018: Molecular Neurobiology
Fumi Nakano, Fumihiro Kawakita, Lei Liu, Yoshinari Nakatsuka, Hirofumi Nishikawa, Takeshi Okada, Hideki Kanamaru, Sujon Pak, Masato Shiba, Hidenori Suzuki
Subarachnoid hemorrhage (SAH) is a devastating disease. Cerebral vasospasm is still an important cause of post-SAH poor outcomes, but its mechanisms remain unveiled. Activation of epidermal growth factor receptor (EGFR) is suggested to cause vasoconstriction in vitro, but no report has demonstrated the involvement of EGFR in vasospasm development after SAH in vivo. Cross-talk of EGFR and vascular endothelial growth factor (VEGF) receptor, which may affect post-SAH vasospasm, was also reported in cancer cells, but has not been demonstrated in post-SAH vasospasm...
October 31, 2018: Molecular Neurobiology
Balasubramaniyan Vairappan, M Sundhar, B H Srinivas
Systemic inflammation and ammonia (hyperammonemia) act synergistically in the pathogenesis of hepatic encephalopathy (HE), the neurobehavioral sequelae of advanced liver disease. In cirrhotic patients, we have recently observed elevated levels of circulating neuronal tight junction (TJ) protein, zonula occludens 1 (ZO-1), reflective of a change to blood-brain barrier (BBB) integrity. Moreover, ZO-1 levels positively correlated with hyperammonemia, although any potential relationship remains unclear. Using a carbon tetrachloride (CCl4 )-induced mouse model of cirrhosis, we primarily looked to explore the relationship between neuronal TJ protein expression and hyperammonemia...
October 30, 2018: Molecular Neurobiology
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