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Clinical Manifestation of Mitochondrial Disorders in Childhood
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
Leigh syndrome (Leigh, 1951) itself has two different meanings. The first represents the radiological or pathological findings of focal bilaterally symmetrical lesions, especially in the thalamus and brainstem regions. The other broadens this meaning to the clinical unit also known as subacute necrotizing encephalomyelopathy. Genetically, LS is very heterogenous and should be defined in by specific mutation or protein deficit where possible, as some particular may specifically differ in their clinical manifestation (e.g., SURF1 or pyruvate-dehydrogenase complex deficiency). In general, LS may be caused by deficits of respiratory chain complex subunits (complex I, II, IV, and V) and their cofactors (e.g., co-enzyme Q10), mutations in nDNA (e.g., SCO2, SURF1), mtDNA encoded tRNA, or the pyruvate dehydrogenase complex (Loeffen et al., 2000; Finsterer, 2008). Mitochondrial respiratory chain complex I (nicotinamide adenine dinucleotide-ubiquinone oxidoreductase) is the largest enzymatic complex of the mitochondrial respiratory chain. Defects in complex I due to nuclear DNA mutations are one of the most frequent casuses of LS. Various mutations in subunits of complex I encoded by nDNA (NDUFV1, NDUFV2, NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS7, and NDUFS8 were reported (Marin et al., 2013).
Drugs used in the treatment of bipolar disorder and their effects on cholesterol biosynthesis – A possible therapeutic mechanism
Published in The World Journal of Biological Psychiatry, 2019
Srisaiyini Kidnapillai, Chiara C. Bortolasci, Bruna Panizzutti, Briana Spolding, Timothy Connor, Kamila Bonifacio, Andrew Sanigorski, Olivia M. Dean, Tamsyn Crowley, Stéphane Jamain, Laura Gray, Marion Leboyer, Michael Berk, Ken Walder
One of the most robust findings is decreased expression of mRNAs encoding subunits of the electron transport chain complexes, especially the subunits of complex I (Sun et al. 2006). Reduced expression of mRNAs coding for subunits of complex I in post-mortem, prefrontal cortex (Andreazza et al. 2010; Scola et al. 2013) and hippocampus (Konradi et al. 2004) have been reported. In addition, there have been reports of down-regulated expression of mRNA for subunits of complexes III and IV (Sun et al. 2006), and complex V (Konradi et al. 2004; Sun et al. 2006). In one study, decreased mRNA levels of NDUFS7 (a subunit of complex I) in the prefrontal cortex was associated with decreased activity of complex I and increased oxidative damage in subjects with BD (Andreazza et al. 2010). Furthermore, several studies investigating the mechanisms of action of the mood stabiliser lithium found effects on mitochondria. Lithium increased the expression of complex I subunits in subjects with BD (Sun et al. 2006) and rodents (Toker et al. 2014) as well as improved complex I activity in the frontal cortex of subjects with BD (Maurer et al. 2009) and leukocytes of depressed subjects with BD (de Sousa et al. 2015). For valproate, however, only one study reported decreased expression of mRNA encoding NDUFS7 (Sun et al. 2006).
Açaí (Euterpe oleracea Mart.) presents anti-neuroinflammatory capacity in LPS-activated microglia cells
Published in Nutritional Neuroscience, 2022
Diulie Valente de Souza, Lauren Pappis, Thuany Teixeira Bandeira, Gabriela Geraldo Sangoi, Tuyla Fontana, Vitor Braga Rissi, Michele Rorato Sagrillo, Marta Maria Duarte, Thiago Duarte, David Frederick Bodenstein, Ana Cristina Andreazza, Ivana Beatrice Mânica da Cruz, Euler Esteves Ribeiro, Alfredo Antoniazzi, Aline Ferreira Ourique, Alencar Kolinski Machado
Despite the high prevalence rates, there is still no complete understanding of the pathophysiology and progression of neuropsychiatric diseases, despite efforts from researchers to advance the understanding of these diseases. Within BD, studies have identified significant increases in oxidative stress in patients with BD. Studies demonstrated significant decreases in mitochondrial complex I function, which showed positive and negative correlation with NDUFS7 protein expression and oxidative stress, respectively, within the pre-frontal cortex of patients with BD [4]. Beyond this, it is has been demonstrated that patients with BD have increased peripheral and neural chronic inflammation [5].
Gene expression study of mitochondrial complex I in schizophrenia and paranoid personality disorder
Published in The World Journal of Biological Psychiatry, 2018
Arvin Haghighatfard, Sarah Andalib, Mozhdeh Amini Faskhodi, Soha Sadeghi, Amir Hossein Ghaderi, Shadi Moradkhani, Jalal Rostampour, Zeinab Tabrizi, Ali Mahmoodi, Talie Karimi, Zakieh Ghadimi
Gene expression studies of mitochondrial complex I help to clarify the pattern of bioenergetics effects in behaviour and psychiatric disorders. Several studies which considered the gene expression of the largest subunits of mitochondrial complex I presented it as potential peripheral biomarker for SCZ (Taurines et al. 2010; Akarsu et al. 2014). The present study examined gene expression of whole subunits in complex I in two psychiatric disorders for the first time, and detected a pattern of gene expression alterations including up- and down-regulations showing the importance of small subunits as well. This is the first gene expression study in PPD. Shared gene expression patterns of both disorders support the hypothesis of a similarity in pathophysiology of PPD and SCZ. Eighteen candidate genes were detected in SCZ and 11 genes in PPD; all of the candidate genes found in PPD were among the 18 differentially expressed genes found in SCZ and their alteration directions were the same in both disorders. These findings confirmed role of genomic core subunits in SCZ. Down-regulation of NDUFS7 and NDUFS8 along with up-regulation of NDUFS1, NDUFV1 and NDUFV2 were detected in both SCZ and PPD patients. Deregulation of these five subunits from 14 core subunits may cause abnormal structured complex I in neural cells, which leads to abnormal energetic state and altered neural activity. None of the seven mitochondrial genes showed a change in expression, which may reduce the importance of a maternal pattern in the heritance of SCZ and PPD. Over-expression of several supernumerary subunits was detected in SCZ and PPD patients. As oxidative stress is increased in psychiatric disorders, it may relate to the role of supernumerary subunits in protection against oxidative stress. Under-expression of five supernumerary subunits was detected in SCZ. Under-expression of NDUFB11 (which is only under-expressed in supernumerary subunits in PPD patients) was reported in brain tissue samples from SCZ patients (Huang et al. 2014). Also, down-regulation of the NDUFA1 gene was reported in progressive neurodegenerative diseases, including Alzheimer’s disease (Fernandez‐Moreira et al. 2007).