The Association Among Bipolar Disorder, Mitochondrial Dysfunction, and Reactive Oxygen Species

Biomolecules, Год журнала: 2025, Номер 15(3), С. 383 - 383

Опубликована: Март 6, 2025

Mitochondria, often known as the cell’s powerhouses, are primarily responsible for generating energy through aerobic oxidative phosphorylation. However, their functions extend far beyond just production. Mitochondria play crucial roles in maintaining calcium balance, regulating apoptosis (programmed cell death), supporting cellular signaling, influencing metabolism, and synthesizing reactive oxygen species (ROS). Recent research has highlighted a strong link between bipolar disorder (BD) mitochondrial dysfunction. Mitochondrial dysfunction contributes to stress, particularly generation of ROS, which implicated pathophysiology BD. Oxidative stress arises when there is an imbalance production ROS ability neutralize them. In neurons, excessive can damage various components, including proteins neuronal membranes intracellular enzymes. Such may interfere with neurotransmitter reuptake function critical enzymes, potentially affecting brain regions involved mood regulation emotional control, key aspects this review, we will explore how types contribute ROS. These include disruptions impaired management, defects quality control mechanisms such mitophagy (the process by damaged mitochondria selectively degraded). We also examine abnormalities synaptic plasticity, lead Additionally, discuss specific dysfunctions observed BD, highlighting these disorder’s pathophysiology. Finally, identify potential therapeutic targets improve function, could pave way new treatments manage or mitigate symptoms

Язык: Английский

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Mitochondrial respiratory activity and DNA damage in peripheral blood mononuclear cells in borderline personality disorder

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 31, 2025

Abstract Alterations in the central and peripheral energy metabolism are increasingly recognized as key pathophysiological processes various psychiatric disorders. This case-control study investigates mitochondrial production oxidative DNA damage Borderline Personality Disorder (BPD). We compared respiration, density, blood mononuclear cells between women with acute BPD, remitted healthy controls ( n = 32, 15, 29), matched for age BMI. Acute BPD was characterized by reduced less efficient ATP to both (e.g., coupling efficiency: r x −0.36 −0.35, p adj ’s < .037). Decreased activity closely associated greater S −0.57, .001), although did not differ diagnostic groups. Our findings suggest promising sensitive biomarkers disorder severity clinical remission BPD.

Язык: Английский

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Exploring the interplay of glucose metabolism, insulin resistance, and neurodegenerative pathologies: insights from streptozotocin and hypoglycaemic in vitro models

Journal of Neural Transmission, Год журнала: 2025, Номер unknown

Опубликована: Фев. 11, 2025

Язык: Английский

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Examining mitochondrial genetic variation in obsessive-compulsive disorder

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 27, 2025

Obsessive-compulsive disorder (OCD) is a severe neuropsychiatric with clear evidence of genetic vulnerability, although specific risk factors are not fully understood. Mitochondrial dysfunction has been implicated in other disorders, particularly through its role oxidative stress, and thus merits exploration OCD. Here we first examined the association set 59 mitochondrial single nucleotide polymorphisms (SNPs) OCD symptom severity. These SNPs located inside 28 nuclear-encoded genes involved phosphorylation, biogenesis, inflammation, apoptosis. We used linear regression to test for this SNP severity using Yale-Brown Obsessive Compulsive Scale (YBOCS). found nominally significant rs3820189 5’ MFN2 gene YBOCS total score (N = 346; P_uncorrected= 0.002). also conducted gene-based gene-set (pathway) analyses on pathways MAGMA. ADCK1 be associated (p 0.00005, q 0.05). No were risk. To further examine variation risk, then (mt) DNA (mtDNA), circular genome each mitochondrion. utilized Toronto sample 215) 1000 Genome Project 485) as healthy controls discovery. For replication, compared individual-level data from Psychiatric Genomics Consortium (PGC) Working Group release 2017 1691) Wellcome Trust 2616) controls. After cleaning, 58 common mtDNA (minor allele frequency greater than 1%) available analysis. Meta-analysis across variants shared between both samples revealed five significantly which survived Nyholt correction: NC_012920.1:m.1719G > A (P 1.489E-05), NC_012920.1:m.3010G 2.423E-05), NC_012920.1:m.10398A G 3.172E-04), NC_012920.1:m.11914G 6.085E-04) NC_012920.1:m.6260G 7.792E-04). best our knowledge, largest study report involvement Further investigations validation findings warranted.

Язык: Английский

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Early Life Stress Induces Brain Mitochondrial Dynamics Changes and Sex‐Specific Adverse Effects in Adulthood

Journal of Neuroscience Research, Год журнала: 2025, Номер 103(4)

Опубликована: Апрель 1, 2025

ABSTRACT Early life stress exposure exerts detrimental effects in adulthood and is a risk factor for psychiatric disorders. Studies addressing the molecular mechanisms of early have primarily focused on hormones circuits. However, little known how mitochondria mitochondrial dynamics (i.e., orchestration fission, fusion, mitophagy, biogenesis) modulate responses. Here, we used maternal separation with weaning (MSEW) paradigm to investigate behavioral stress‐elicited male female C57BL/6 mice adulthood. We first applied test battery assess MSEW‐driven, anxiety‐related stress‐coping alterations. then looked MSEW‐induced, mitochondria‐centered changes cingulate cortex, hippocampus cerebellum, as well plasma by combining protein, mRNA, DNA copy number (mtDNAcn) metabolomics analyses. found that MSEW are more anxious, show decreased antioxidant capacity cortex higher mRNA levels fission regulator Fis1 mitophagy activator Pink1 hippocampus, indicating shift towards degradation. Hippocampal level alterations apoptotic markers further suggest an MSEW‐driven activation apoptosis accompanied dysregulation purine catabolism cerebellum mice. Sex‐specific analysis revealed distinct MSEW‐induced at level. Our work reveals previously unexplored role regulating highlights persistent outcome

Язык: Английский

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AMPK-YAP signaling pathway-mediated mitochondrial dynamics and mitophagy participate in the protective effect of silibinin on HaCaT cells under high glucose conditions

Archives of Biochemistry and Biophysics, Год журнала: 2025, Номер 769, С. 110433 - 110433

Опубликована: Апрель 21, 2025

Язык: Английский

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Liquid Chromatography-Tandem Mass Spectrometry Method Development and Validation for the Determination of a New Mitochondrial Antioxidant in Mouse Liver and Cerebellum, Employing Advanced Chemometrics

Molecules, Год журнала: 2025, Номер 30(9), С. 1900 - 1900

Опубликована: Апрель 24, 2025

Anxiety and stress-related disorders affect all ages in geographical areas. As high anxiety chronic stress result the modulation of mitochondrial pathways, intensive research is being carried out on pharmaceutical interventions that alleviate pertinent symptomatology. Therefore, innovative approaches currently pursued include substances target mitochondria bearing an antioxidant moiety. In this study, a newly synthesized consisting triphenylphosphine (TPP), six-carbon alkyl spacer, hydroxytyrosol (HT) was administered orally to mice via drinking water. Cerebellum liver samples were collected analyzed using ultra-high-performance liquid chromatography-tandem triple quadrupole mass spectrometry (UHPLC-MS/MS) assess levels TPP-HT respective tissues evaluate vivo administration efficacy. Sample preparation included extraction with appropriate solvents preconcentration step achieve required sensitivity. Both methods validated terms selectivity, linearity, accuracy, limits detection quantification. Additionally, workflow for evaluating statistically summarizing multiple fortified calibration curves devised. penetrates blood–brain barrier (BBB), level 11.5 ng g−1 quantified cerebellum, whereas 4.8 detected liver, highlighting plausibility administering targeting.

Язык: Английский

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FMRP gains mitochondrial fission control

Nature Cell Biology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 15, 2024

Язык: Английский

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Exploring the molecular mechanisms of comorbidity of myocardial infarction and anxiety disorders by combining multiple data sets with in vivo experimental validation

International Immunopharmacology, Год журнала: 2024, Номер 146, С. 113852 - 113852

Опубликована: Дек. 28, 2024

Язык: Английский

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