Mitochondrial brain

Eunyoung Jung, Seong-Ho Koh, Myeongjong Yoo, Yoon Kyung Choi
Regeneration of adult neural circuits after an injury is limited in the central nervous system (CNS). Heme oxygenase (HO) is an enzyme that produces HO metabolites, such as carbon monoxide (CO), biliverdin and iron by heme degradation. CO may act as a biological signal transduction effector in CNS regeneration by stimulating neuronal intrinsic and extrinsic mechanisms as well as mitochondrial biogenesis. CO may give directions by which the injured neurovascular system switches into regeneration mode by stimulating endogenous neural stem cells and endothelial cells to produce neurons and vessels capable of replacing injured neurons and vessels in the CNS...
March 25, 2020: International Journal of Molecular Sciences
Yunseon Jang, Jae Hyeon Lee, Min Joung Lee, Soo Jeong Kim, Xianshu Ju, Jianchen Cui, Jiebo Zhu, Yu Lim Lee, Eunji Namgung, Han Wool John Sung, Hong Won Lee, Min Jeong Ryu, Eungseok Oh, Woosuk Chung, Gi Ryang Kweon, Chun Whan Choi, Jun Young Heo
Cognitive decline is observed in aging and neurodegenerative diseases, including Alzheimer's disease (AD) and dementia. Intracellular energy produced via mitochondrial respiration is used in the regulation of synaptic plasticity and structure, including dendritic spine length and density, as well as for the release of neurotrophic factors involved in learning and memory. To date, a few synthetic agents for improving mitochondrial function have been developed for overcoming cognitive impairment. However, no natural compounds that modulate synaptic plasticity by directly targeting mitochondria have been developed...
March 25, 2020: Nutrients
Satvik Kotha, Swapna B, Vithal M Kulkarni, Ramachandra Setty S, Harish Kumar B, Harisha R
Alzheimer's Disease is a complex progressive neurodegenerative disorder characterized by neurofibrillary tangles and senile plaques in various parts of the brain particularly cerebral cortex affecting memory and cognition. Nuclear receptors such as Peroxisome proliferator-activated receptor γ [PPAR-γ] is reported to have a role in lipid and glucose homeostasis in the brain, reduces the synthesis of Aβ (beta-amyloid plaques) and also regulates mitochondrial biogenesis and inhibit the neuro-inflammation, which contributes for the improvement in the cognitive function in AD...
March 27, 2020: Journal of Biomolecular Structure & Dynamics
Bo Lin, Youguang Gao, Zhiwang Li, Zhiming Zhang, Xianzhong Lin, Jinpeng Gao
Recently, several studies have reported that the pharmacological effects exerted by cannabidiol (CBD) are partially related to the regulation of autophagy. Increasing evidence indicates that autophagy provides protection against ischemia-induced brain injury. However, the protective effect of CBD against mitochondrial-dependent apoptosis in hemorrhagic shock (HS)-induced brain injury has not been studied. In the present study, we observed the protective effects of CBD against neural mitochondrial-dependent apoptosis in a rat model of HS...
March 25, 2020: Fundamental & Clinical Pharmacology
Baozhu Fan, Riffat Jabeen, Bing Bo, Chunlei Guo, Mengjie Han, Hui Zhang, Juan Cen, Xinying Ji, Jianshe Wei
Aim: This study was aimed at investigating the effects and molecular mechanisms of physical activity intervention on Parkinson's disease (PD) and providing theoretical guidance for the prevention and treatment of PD. Methods: Four electronic databases up to December 2019 were searched (PubMed, Springer, Elsevier, and Wiley database), 176 articles were selected. Literature data were analyzed by the logic analysis method. Results: (1) Risk factors of PD include dairy products, pesticides, traumatic brain injury, and obesity...
2020: Oxidative Medicine and Cellular Longevity
Jun-Hui Zheng, Meng-Hua Chen, Zhao-Yin Fu, Nuo Li, Lu Xie
Background: Mitochondria play a critical role as effectors and targets of brain injury in the post-resuscitation period. Although we found previously that the extracellular signal-regulated kinase (ERK)1/2 inhibitor PD98059 (PD) protects the brain against mitochondrial-mediated cell death at 24 h post-resuscitation in rats subjected to cardiac arrest/cardiopulmonary resuscitation (CA/CPR), it is not clear whether PD also exerts mitochondrial protective effect for a lasting time. Therefore, we examined the effect of PD on brain mitochondria at 48 h post-resuscitation to evaluate the time-effect of PD in the current study...
2020: Drug Design, Development and Therapy
Louis-Philippe Bernier, Elisa M York, Alireza Kamyabi, Hyun B Choi, Nicholas L Weilinger, Brian A MacVicar
Microglia are highly motile cells that continuously monitor the brain environment and respond to damage-associated cues. While glucose is the main energy substrate used by neurons in the brain, the nutrients metabolized by microglia to support surveillance of the parenchyma remain unexplored. Here, we use fluorescence lifetime imaging of intracellular NAD(P)H and time-lapse two-photon imaging of microglial dynamics in vivo and in situ, to show unique aspects of the microglial metabolic signature in the brain...
March 25, 2020: Nature Communications
Mariona Jové, Irene Pradas, Natalia Mota-Martorell, Rosanna Cabré, Victoria Ayala, Isidre Ferrer, Reinald Pamplona
Human brain evolution toward complexity has been achieved with increasing energy supply as the main adaptation in brain metabolism. Energy metabolism, like other biochemical reactions in aerobic cells, is under enzymatic control and strictly regulated. Nevertheless, physiologically uncontrolled and deleterious reactions take place. It has been proposed that these reactions constitute the basic molecular mechanisms that underlie the maintenance or loss-of-function of neurons and, by extension, cerebral functions during brain aging...
2020: Frontiers in Aging Neuroscience
Richard L Jayaraj, Sheikh Azimullah, Rami Beiram
The incidence of Alzheimer's disease (AD) has risen exponentially worldwide over the past decade. A growing body of research indicates that AD is linked to diabetes mellitus (DM) and suggests that impaired insulin signaling acts as a crucial risk factor in determining the progression of this devastating disease. Many studies suggest people with diabetes, especially type 2 diabetes, are at higher risk of eventually developing Alzheimer's dementia or other dementias. Despite nationwide efforts to increase awareness, the prevalence of Diabetes Mellitus (DM) has risen significantly in the Middle East and North African (MENA) region which might be due to rapid urbanization, lifestyle changes, lack of physical activity and rise in obesity...
February 2020: Saudi Journal of Biological Sciences
William Banks
Diabetes mellitus (DM) is one of the most common diseases in the world. Among its effects are an increase in the risk of cognitive impairment, including Alzheimer's disease, and blood-brain barrier (BBB) dysfunction. DM is characterized by high blood glucose levels that are caused by either lack of insulin (Type I) or resistance to the actions of insulin (Type II). The phenotypes of these two types are dramatically different, with Type I animals being thin, with low levels of leptin as well as insulin, whereas Type II animals are often obese with high levels of both leptin and insulin...
March 25, 2020: Current Pharmaceutical Design
Jithine Jayakumar Rajeswari, Ayelen Melisa Blanco, Suraj Unniappan
Phoenixin is a 20 amino acid peptide (PNX-20) cleaved from the small integral membrane protein 20 (SMIM20), with multiple biological roles in mammals. However, its role in non-mammalian vertebrates is poorly understood. This research aimed to determine whether PNX-20 influences feeding and metabolism in zebrafish. The mRNAs encoding SMIM20 and its putative receptor, super conserved receptor expressed in brain 3 (SREB3), are present in both central and peripheral tissues of zebrafish. Immunohistochemical analysis confirmed the presence of PNX-like immunoreactivity in the gut and zebrafish liver (ZFL) cell line...
March 25, 2020: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Jason J Rose, Kaitlin A Bocian, Qinzi Xu, Ling Wang, Anthony W DeMartino, Xiukai Chen, Catherine G Corey, Danielle A Guimarães, Ivan Azarov, Xueyin N Huang, Qin Tong, Lanping Guo, Mehdi Nouraie, Charles F McTiernan, Christopher P O'Donnell, Jesús Tejero, Sruti Shiva, Mark Gladwin
Carbon monoxide (CO) remains the most common cause of human poisoning. The consequences of CO poisoning include cardiac dysfunction, brain injury, and death. CO causes toxicity by binding to hemoglobin and by inhibiting mitochondrial cytochrome c oxidase (CcO), thereby decreasing oxygen delivery and inhibiting oxidative phosphorylation.  We have recently developed a CO antidote based on human neuroglobin (Ngb-H64Q-CCC). This molecule enhances clearance of CO from red blood cells in vitro and in vivo. Herein, we tested whether Ngb-H64Q-CCC can also scavenge CO from CcO and attenuate CO-induced inhibition of mitochondrial respiration...
March 23, 2020: Journal of Biological Chemistry
Lihua Yang, Ningning Guo, Wei Fan, Chunmin Ni, Mengbing Huang, Liping Bai, Le Zhang, Xianwen Zhang, Yunbo Wen, Ye Li, Xiaoshuang Zhou, Jie Bai
Methamphetamine (METH) has been reported to induce endoplasmic reticulum (ER) stress and neuronal apoptosis in the central nervous system (CNS) during the development of addiction. Thioredoxin-1 (Trx-1) is a redox regulating protein and plays an important role in inhibiting apoptosis and protects neurons from cytotoxicity through ER and mitochondria-mediated pathways. Our previous study has been reported that Trx-1 protects mice from METH-induced rewarding effect. However, whether Trx-1 plays the role in resisting METH injury is still unclear...
March 20, 2020: Neurotoxicology
Margalida Torrens-Mas, Daniel-Gabriel Pons, Jorge Sastre-Serra, Jordi Oliver, Pilar Roca
Compared to other organs, the brain is especially exposed to oxidative stress. In general, brains from young females tend to present lower oxidative damage in comparison to their male counterparts. This has been attributed to higher antioxidant defenses and a better mitochondrial function in females, which has been linked to neuroprotection in this group. However, these differences usually disappear with aging, and the incidence of brain pathologies increases in aged females. Sexual hormones, which suffer a decrease with normal aging, have been proposed as the key factors involved in these gender differences...
March 14, 2020: Redox Biology
Alexandros K Kanellopoulos, Vittoria Mariano, Marco Spinazzi, Young Jae Woo, Colin McLean, Ulrike Pech, Ka Wan Li, J Douglas Armstrong, Angela Giangrande, Patrick Callaerts, August B Smit, Brett S Abrahams, Andre Fiala, Tilmann Achsel, Claudia Bagni
Social impairment is frequently associated with mitochondrial dysfunction and altered neurotransmission. Although mitochondrial function is crucial for brain homeostasis, it remains unknown whether mitochondrial disruption contributes to social behavioral deficits. Here, we show that Drosophila mutants in the homolog of the human CYFIP1, a gene linked to autism and schizophrenia, exhibit mitochondrial hyperactivity and altered group behavior. We identify the regulation of GABA availability by mitochondrial activity as a biologically relevant mechanism and demonstrate its contribution to social behavior...
March 19, 2020: Cell
Gunter P Eckert, Schamim H Eckert, Janett Eckmann, Stephanie Hagl, Walter E Muller, Kristina Friedland
BACKGROUND: Approved drugs for Alzheimer's disease (AD) only have a symptomatic effect and do not intervene causally in the course of the disease. Olesoxime (TRO19622) has been tested in AD disease models characterized by improved amyloid precursor protein processing (AβPP) and mitochondrial dysfunction. METHODS: Three months old Thy-1-AβPPSL (tg) and wild type mice (wt) received TRO19622 (100 mg/kg b.w.) in supplemented food pellets for 15 weeks (tg TRO19622)...
March 18, 2020: Experimental Neurology
Yongxing Lai, Peiqiang Lin, Manli Chen, Yixian Zhang, Jianhao Chen, Mouwei Zheng, Ji Liu, Houwei Du, Ronghua Chen, Xiaodong Pan, Nan Liu, Hongbin Chen
BACKGROUND: Ischemic stroke can induce changes in mitochondrial morphology and function. As a regulatory gene in mitochondria, optic atrophy 1 (OPA1) plays a pivotal role in the regulation of mitochondrial dynamics and other related functions. However, its roles in cerebral ischemia-related conditions are barely understood. METHODS: Cultured rat primary cortical neurons were respectively transfected with OPA1-v1ΔS1-encoding and OPA1-v1-encoding lentivirus before exposure to 2-h oxygen-glucose deprivation (OGD) and subsequent reoxygenation (OGD/R)...
March 13, 2020: Redox Biology
Stefanie Berger, Miranda Stattmann, Ana Cicvaric, Francisco J Monje, Pierluca Coiro, Matej Hotka, Gerda Ricken, Johannes Hainfellner, Susanne Greber-Platzer, Makiko Yasuda, Robert J Desnick, Daniela D Pollak
Acute intermittent porphyria (AIP) is an autosomal dominant inborn error of heme biosynthesis due to a pathogenic mutation in the Hmbs gene, resulting in half-normal activity of hydroxymethylbilane synthase. Factors that induce hepatic heme biosynthesis induce episodic attacks in heterozygous patients. The clinical presentation of acute attacks involves the signature neurovisceral pain and may include psychiatric symptoms. Here we used a knock-in mouse line that is biallelic for the Hmbs c.500G > A (p...
March 20, 2020: Acta Neuropathologica Communications
Vincent Joseph, Sofien Laouafa, François Marcouiller, Damien Roussel, Vincent Pialoux, Aida Bairam
NEW FINDINGS: What is the central question of this study? Does progesterone reduce the effect of chronic intermittent hypoxia (CIH) on arterial blood pressure, respiratory control, and oxidative stress in the central nervous system in ovariectomized rats? What is the main finding and its importance? Progesterone does not prevent the elevation of arterial blood pressure in rats exposed to CIH, but normalizes respiratory control, and reduces cerebral oxidative stress. This study draws focus to a potential role of progesterone and the consequences of sleep apnoea in menopausal women...
March 20, 2020: Experimental Physiology
João Laranjinha, Carla Nunes, Ana Ledo, Cátia Lourenço, Bárbara Rocha, Rui M Barbosa
In this review, we address the regulatory and toxic role of · NO along several pathways, from the gut to the brain. Initially, we address the role on · NO in the regulation of mitochondrial respiration with emphasis on the possible contribution to Parkinson's disease via mechanisms that involve its interaction with a major dopamine metabolite, DOPAC. In parallel with initial discoveries of the inhibition of mitochondrial respiration by · NO, it became clear the potential for toxic · NO-mediated mechanisms involving the production of more reactive species and the post-translational modification of mitochondrial proteins...
March 19, 2020: Neurochemical Research
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