scholarly journals Ethanol Consumption Affects Neuronal Function: Role of the Mitochondria

2018 ◽  
Author(s):  
Cheril Tapia-Rojas ◽  
María José Pérez ◽  
Claudia Jara ◽  
Erick H. Vergara ◽  
Rodrigo A. Quintanilla
Keyword(s):  
Ethanol Consumption ◽  
Neuronal Function

scholarly journals Ndufs4 ablation decreases synaptophysin expression in hippocampus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Subrata Kumar Shil ◽  
Yoshiteru Kagawa ◽  
Banlanjo Abdulaziz Umaru ◽  
Fumika Nanto-Hara ◽  
Hirofumi Miyazaki ◽  
...  
Keyword(s):  
Nadh Dehydrogenase ◽  
Leigh Syndrome ◽  
Mitochondrial Respiratory Chain ◽  
Mitochondrial Activity ◽  
Mitochondrial Complex ◽  
Neuronal Function ◽  
Mouse Hippocampus ◽  
Extracellular Regulated Kinase ◽  
Presynaptic Protein

AbstractAltered function of mitochondrial respiratory chain in brain cells is related to many neurodegenerative diseases. NADH Dehydrogenase (Ubiquinone) Fe-S protein 4 (Ndufs4) is one of the subunits of mitochondrial complex I and its mutation in human is associated with Leigh syndrome. However, the molecular biological role of Ndufs4 in neuronal function is poorly understood. In this study, upon Ndufs4 expression confirmation in NeuN-positive neurons, and GFAP-positive astrocytes in WT mouse hippocampus, we found significant decrease of mitochondrial respiration in Ndufs4-KO mouse hippocampus. Although there was no change in the number of NeuN positive neurons in Ndufs4-KO hippocampus, the expression of synaptophysin, a presynaptic protein, was significantly decreased. To investigate the detailed mechanism, we silenced Ndufs4 in Neuro-2a cells and we observed shorter neurite lengths with decreased expression of synaptophysin. Furthermore, western blot analysis for phosphorylated extracellular regulated kinase (pERK) revealed that Ndufs4 silencing decreases the activity of ERK signalling. These results suggest that Ndufs4-modulated mitochondrial activity may be involved in neuroplasticity via regulating synaptophysin expression.

scholarly journals The Role of the Innate Immune System in Alzheimer’s Disease and Frontotemporal Lobar Degeneration: An Eye on Microglia

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Elisa Ridolfi ◽  
Cinzia Barone ◽  
Elio Scarpini ◽  
Daniela Galimberti
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontotemporal Lobar Degeneration ◽  
Environmental Changes ◽  
Current Evidence ◽  
Neuronal Function ◽  
Immune Effector ◽  
Effector Cells ◽  
The Central Nervous System

In the last few years, genetic and biomolecular mechanisms at the basis of Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) have been unraveled. A key role is played by microglia, which represent the immune effector cells in the central nervous system (CNS). They are extremely sensitive to the environmental changes in the brain and are activated in response to several pathologic events within the CNS, including altered neuronal function, infection, injury, and inflammation. While short-term microglial activity has generally a neuroprotective role, chronic activation has been implicated in the pathogenesis of neurodegenerative disorders, including AD and FTLD. In this framework, the purpose of this review is to give an overview of clinical features, genetics, and novel discoveries on biomolecular pathogenic mechanisms at the basis of these two neurodegenerative diseases and to outline current evidence regarding the role played by activated microglia in their pathogenesis.

scholarly journals RNAi-Mediated Reverse Genetic Screen Identified Drosophila Chaperones Regulating Eye and Neuromuscular Junction Morphology

2017 ◽  
Vol 7 (7) ◽  
pp. 2023-2038 ◽  
Author(s):  
Sandeep Raut ◽  
Bhagaban Mallik ◽  
Arpan Parichha ◽  
Valsakumar Amrutha ◽  
Chandan Sahi ◽  
...  
Keyword(s):  
Molecular Chaperones ◽  
Bioinformatics Analysis ◽  
Reverse Genetic ◽  
Unfolded Proteins ◽  
Neuronal Function ◽  
Synapse Loss ◽  
Functional Relevance ◽  
Reverse Genetic Screen ◽  
Behavioral Assays

Abstract Accumulation of toxic proteins in neurons has been linked with the onset of neurodegenerative diseases, which in many cases are characterized by altered neuronal function and synapse loss. Molecular chaperones help protein folding and the resolubilization of unfolded proteins, thereby reducing the protein aggregation stress. While most of the chaperones are expressed in neurons, their functional relevance remains largely unknown. Here, using bioinformatics analysis, we identified 95 Drosophila chaperones and classified them into seven different classes. Ubiquitous actin5C-Gal4-mediated RNAi knockdown revealed that ∼50% of the chaperones are essential in Drosophila. Knocking down these genes in eyes revealed that ∼30% of the essential chaperones are crucial for eye development. Using neuron-specific knockdown, immunocytochemistry, and robust behavioral assays, we identified a new set of chaperones that play critical roles in the regulation of Drosophila NMJ structural organization. Together, our data present the first classification and comprehensive analysis of Drosophila chaperones. Our screen identified a new set of chaperones that regulate eye and NMJ morphogenesis. The outcome of the screen reported here provides a useful resource for further elucidating the role of individual chaperones in Drosophila eye morphogenesis and synaptic development.

Abstract T P87: Hydrogen Sulfide Enhances Neurogenesis through the IRAK-1/GSK3β/AKT Signaling Pathways after Ischemic Stroke

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Pradip K Kamat ◽  
Anuradha Kalani ◽  
Neetu Tyagi
Keyword(s):  
Hydrogen Sulfide ◽  
Signaling Pathways ◽  
Ventricular Zone ◽  
Ischemia Reperfusion ◽  
Analysis Data ◽  
Akt Signaling ◽  
Artery Occlusion ◽  
Cortical Region ◽  
Neuronal Function

Background and purpose: Increasing evidence signifying that inflammation has an ample role in the ischemia and; neurogenesis is somehow affected by inflammation. Current approved therapy for stroke is limited and new strategies need to be investigated. Hydrogen sulfide (H2S) showed neuro-protective however, role of H2S in stroke-induced neurogenesis is not known. Therefore, the present study was to determine the role of H2S in ischemia induced neurogenesis. Methods: To perform this study; we employed 8-10 weak old C57BL/6 mice with following groups: WT-Sham; WT+ ischemia reperfusion (IR) for 7 days; IR+GYY4137 (H2S donor, 30μM for 7 days; Intra peritoneal injection); and Sham+ GYY4137 (30μM for 7 day). Ischemia was created by the middle cerebral artery occlusion, (MCAO) for 50 min followed by reperfusion for 7 days. The brain tissue from different groups was used for biochemical, infarct area molecular and immunohistochemistry analysis. Data were analyzed by one way ANOVA followed by Tukey test. Results: We found increased protein expression of IRAK-1 (F=3, 27.01; P<.005), GSK3β 9 (F=3, 89.47; P<.005), p-AKT (F=3, 89.47; P<.005) and reduced expression of AKT p-AKT(F=3, 112.2; P<.005) in I/R group as compared to sham that indicates alteration of inflammatory signaling pathways. Further, we also found decreased level of Nestin (F=3, 35.32; P<.005), GFAP (F=3, 95.14; P<.001), NeuN (F=3, 123.4; P<.001), TUJ-1 (F=3, 112; P<.005), MAP-2 (F=3, 31.54; P<.0001), IL-6 (F=3, 55.7; p<.05) and BDNF (F=3, 166.5; P<.005) in cortical region of I/R group which indicates loss of neuronal function. Additionally, immunohistochemistry assay also revealed the loss of Nestin (P<.05), BDNF (P<.05), MAP-2 (P<.05) along with increased GSK-3β (P<.005) expression in sub ventricular zone (SVZ) and hippocampal region. Further, GYY4137 treatment for 7 days in ischemic group significantly restored the Nestin, GFAP, IL-6, NeuN, TUJ-1, MAP-2 and BDNF levels via regulating IRAK-1/GSK3β/AKT signaling pathways. Conclusion: Present study clearly demonstrate that H2S plays an important role in ischemia induced neurogenesis as well as protecting neuronal function through inhibition of IRAK1/GSK3β/AKT signaling pathways. Acknowledgement: This work was supported by NTHL107640-NT.

scholarly journals Dopamine D3 receptors contribute to methamphetamine-induced alterations in dopaminergic neuronal function: Role of hyperthermia

2014 ◽  
Vol 732 ◽  
pp. 105-110 ◽  
Author(s):  
Michelle G. Baladi ◽  
Amy H. Newman ◽  
Shannon M. Nielsen ◽  
Glen R. Hanson ◽  
Annette E. Fleckenstein
Keyword(s):  
Neuronal Function ◽  
Dopamine D3 Receptors ◽  
D3 Receptors ◽  
Dopamine D3

scholarly journals Unique Role of Caffeine Compared to Other Methylxanthines (Theobromine, Theophylline, Pentoxifylline, Propentofylline) in Regulation of AD Relevant Genes in Neuroblastoma SH-SY5Y Wild Type Cells

2020 ◽  
Vol 21 (23) ◽  
pp. 9015
Author(s):  
Daniel Janitschke ◽  
Anna A. Lauer ◽  
Cornel M. Bachmann ◽  
Martin Seyfried ◽  
Heike S. Grimm ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Transcriptional Regulation ◽  
Expression Patterns ◽  
Wild Type ◽  
Neuronal Function ◽  
Purine Base ◽  
Unique Role ◽  
Beneficial Effects ◽  
Other Substances

Methylxanthines are a group of substances derived from the purine base xanthine with a methyl group at the nitrogen on position 3 and different residues at the nitrogen on position 1 and 7. They are widely consumed in nutrition and used as pharmaceuticals. Here we investigate the transcriptional regulation of 83 genes linked to Alzheimer’s disease in the presence of five methylxanthines, including the most prominent naturally occurring methylxanthines—caffeine, theophylline and theobromine—and the synthetic methylxanthines pentoxifylline and propentofylline. Methylxanthine-regulated genes were found in pathways involved in processes including oxidative stress, lipid homeostasis, signal transduction, transcriptional regulation, as well as pathways involved in neuronal function. Interestingly, multivariate analysis revealed different or inverse effects on gene regulation for caffeine compared to the other methylxanthines, which was further substantiated by multiple comparison analysis, pointing out a distinct role for caffeine in gene regulation. Our results not only underline the beneficial effects of methylxanthines in the regulation of genes in neuroblastoma wild-type cells linked to neurodegenerative diseases in general, but also demonstrate that individual methylxanthines like caffeine mediate unique or inverse expression patterns. This suggests that the replacement of single methylxanthines by others could result in unexpected effects, which could not be anticipated by the comparison to other substances in this substance class.

scholarly journals 24(S)-Hydroxycholesterol as a Modulator of Neuronal Signaling and Survival

2015 ◽  
Vol 22 (2) ◽  
pp. 132-144 ◽  
Author(s):  
Min-Yu Sun ◽  
Andrew J. Linsenbardt ◽  
Christine M. Emnett ◽  
Lawrence N. Eisenman ◽  
Yukitoshi Izumi ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Neurodegenerative Disease ◽  
Therapeutic Potential ◽  
Brain Plasticity ◽  
Neuronal Function ◽  
Synthetic Analogues ◽  
Down Regulation ◽  
Cholesterol Removal ◽  
Positive Effects

The major cholesterol metabolite in brain, 24(S)-hydroxycholesterol (24S-HC), serves as a vehicle for cholesterol removal. Its effects on neuronal function, however, have only recently begun to be investigated. Here, we review that nascent work. Our own studies have demonstrated that 24S-HC has potent positive modulatory effects on N-methyl-d-aspartate (NMDA) receptor (NMDAR) function. This could have implications not only for brain plasticity but also for pathological NMDAR overuse. Other work has demonstrated effects of 24S-HC on neuronal survival and as a possible biomarker of neurodegenerative disease. Depending on circumstances, both upregulation/mimicry of 24S-HC signaling and down-regulation/antagonism may have therapeutic potential. We are interested in the possibility that synthetic analogues of 24S-HC with positive effects at NMDARs may hold neurotherapeutic promise, given the role of NMDA receptor hypofunction in certain neuropsychiatric disorders.

Sign in / Sign up

Export Citation Format

Share Document