Mitochondrial dysfunction: A fatal blow in depression

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 167, P. 115652 - 115652

Published: Oct. 4, 2023

Mitochondria maintain the normal physiological function of nerve cells by producing sufficient cellular energy and performing crucial roles in maintaining metabolic balance through intracellular Ca2+ homeostasis, oxidative stress, axonal development. Depression is a prevalent psychiatric disorder with an unclear pathophysiology. Damage to hippocampal neurons key component plasticity regulation synapses plays critical role mechanism depression. There evidence suggesting that mitochondrial dysfunction associated synaptic impairment. The maintenance homeostasis includes quantitative quality control mitochondria. Mitochondrial biogenesis produces new healthy mitochondria, dynamics cooperates mitophagy remove damaged These processes population stability exert neuroprotective effects against early In contrast, observed various brain regions patients major depressive disorders. accumulation defective mitochondria accelerates dysfunction. addition, impaired aggravate alterations microenvironment, promoting neuroinflammation depletion, thereby exacerbating development This review summarizes influence underlying molecular pathways on pathogenesis Additionally, we discuss as potential therapeutic strategy for

Language: Английский

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Type I Diabetes Pathoetiology and Pathophysiology: Roles of the Gut Microbiome, Pancreatic Cellular Interactions, and the ‘Bystander’ Activation of Memory CD8+ T Cells

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3300 - 3300

Published: Feb. 7, 2023

Type 1 diabetes mellitus (T1DM) arises from the failure of pancreatic β-cells to produce adequate insulin, usually as a consequence extensive β-cell destruction. T1DM is classed an immune-mediated condition. However, processes that drive apoptosis remain be determined, resulting in prevent ongoing cellular Alteration mitochondrial function clearly major pathophysiological process underpinning loss T1DM. As with many medical conditions, there growing interest role gut microbiome, including interactions bacteria Candida albicans fungal infection. Gut dysbiosis and permeability are intimately associated raised levels circulating lipopolysaccharide suppressed butyrate levels, which can act dysregulate immune responses systemic function. This manuscript reviews broad bodies data on pathophysiology, highlighting importance alterations melatonergic pathway driving dysfunction. The suppression melatonin makes susceptible oxidative stress dysfunctional mitophagy, partly mediated by melatonin’s induction PTEN-induced kinase (PINK1), thereby suppressing mitophagy increasing autoimmune histocompatibility complex (MHC)-1. immediate precursor melatonin, N-acetylserotonin (NAS), brain-derived neurotrophic factor (BDNF) mimic, via activation BDNF receptor, TrkB. both full-length truncated TrkB play powerful roles survival, NAS another important aspect relevant destruction incorporation pathophysiology integrates wide previously disparate intercellular processes. Akkermansia muciniphila, Lactobacillus johnsonii, butyrate, shikimate pathway—including bacteriophages—contributes not only apoptosis, but also bystander CD8+ T cells, increases their effector prevents deselection thymus. microbiome therefore significant determinant dysfunction well ‘autoimmune’ effects derived cytotoxic cells. has future research treatment implications.

Language: Английский

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Redefining Autoimmune Disorders’ Pathoetiology: Implications for Mood and Psychotic Disorders’ Association with Neurodegenerative and Classical Autoimmune Disorders

Cells, Journal Year: 2023, Volume and Issue: 12(9), P. 1237 - 1237

Published: April 25, 2023

Although previously restricted to a limited number of medical conditions, there is growing appreciation that 'autoimmune' (or immune-mediated) processes are important aspects wide array diverse including cancers, neurodegenerative diseases and psychiatric disorders. All these classes conditions associated with alterations in mitochondrial function across an cell types. Accumulating data indicate the presence melatonergic pathway possibly all body cells, consequences for pathways crucial driving CD8+ T B-cell 'autoimmune'-linked processes. Melatonin suppression coupled upregulation oxidative stress suppress PTEN-induced kinase 1 (PINK1)/parkin-driven mitophagy, raising levels major histocompatibility complex (MHC)-1, which underpins chemoattraction cells activation antibody-producing B-cells. Many factors closely autoimmunity, gut microbiome/permeability, circadian rhythms, aging, aryl hydrocarbon receptor, brain-derived neurotrophic factor (BDNF) its receptor tyrosine B (TrkB) interact pathway. A future research directions novel treatment implications indicated this collection poorly conceptualized treated presentations. It proposed etiology many 'autoimmune'/'immune-mediated' disorders should be as significantly determined by dysregulation, being aspect pathoetiologies.

Language: Английский

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Bibliometric insights into astrocytic roles in depression and treatment

Frontiers in Cellular Neuroscience, Journal Year: 2025, Volume and Issue: 18

Published: Jan. 15, 2025

Depression is a mental disorder that significantly impairs both physical and health. Recent studies have shown reactive astrogliosis gained significant attention for their involvement in the pathophysiology of depression. However, there no bibliometric analysis this research field. This study aims to provide comprehensive overview knowledge structure hotspots regarding role astrocytes mechanisms treatment depression through analysis. The scope literature review encompasses basic clinical research. Publications related from 2014 2023 were searched Web Science Core Collection (WoSCC) database. VOSviewer, CiteSpace, R package "bibliometrix" used conduct From 2023, total 1,502 documents 78 countries on analyzed 169 journals, with most co-cited journals being Journal Neuroscience PNAS. China Medical University was productive institution. identified key authors like Verkhratsky Alexei Baoman Li, major references by Rajkowska Liddelow. Keywords such as "synaptic plasticity," "astrocytes," "neuroinflammation" revealed trends focusing molecular mechanisms, gut microbiota, inflammation. first comprehensively summarize advancements its treatment. Through analysis, we aim enhance understanding significance new perspectives insights future investigations. We hope will facilitate broader integration research, offering novel approaches

Language: Английский

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Interleukin-1β rs16944 and rs1143627 polymorphisms and risk of developing major depressive disorder: A case-control study among Bangladeshi population

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0317665 - e0317665

Published: Jan. 22, 2025

Background Epidemiological research suggests that altered levels of cytokine are associated with pathophysiology and the development major depressive disorder (MDD). Based on earlier study, IL-1β rs16944 rs1143627 polymorphisms may increase risk depression. Here, we aimed to evaluate correlation between these MDD susceptibility among population in Bangladesh. Methods Blood samples were collected from 100 patients 70 matched controls. Study participants evaluated by DSM-5 criteria PCR-RFLP method applied for genotyping. Results The IL1β found have a significant association MDD. In case CT heterozygous genotype (OR = 2.22, 95% CI 1.08–4.55, p-value 0.029) combined CT+TT 2.35, 1.15–4.79, 0.019) was strongly increased comparison CC common genotype. Moreover, over-dominant model indicated 2.15-fold higher 2.15, 1.05–4.40, 0.036). On other hand, revealed TC+CC dominant showed 2.06-fold compared TT homozygote 2.06, 1.06–3.99, 0.032). Conclusion Studies an These findings will provide us valuable insights into

Language: Английский

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Melatonin, BAG-1 and cortisol circadian interactions in tumor pathogenesis and patterned immune responses

Exploration of Targeted Anti-tumor Therapy, Journal Year: 2023, Volume and Issue: unknown, P. 962 - 993

Published: Oct. 25, 2023

A dysregulated circadian rhythm is significantly associated with cancer risk, as aging. Both aging and dysregulation show suppressed pineal melatonin, which indicated in many studies to be linked risk progression. Another independently investigated aspect of the cortisol awakening response (CAR), stress-associated hypothalamus-pituitary-adrenal (HPA) axis activation. CAR HPA activity are primarily mediated via activation glucocorticoid receptor (GR), drives patterned gene expression binding promotors element (GRE)-expressing genes. Recent data shows that GR can prevented from nuclear translocation by B cell lymphoma-2 (Bcl-2)-associated athanogene 1 (BAG-1), translocates mitochondria, where it have diverse effects. Melatonin also suppresses maintaining a complex heat shock protein 90 (Hsp90). Melatonin, directly and/or epigenetically, upregulate BAG-1, suggesting dramatic 10-fold decrease melatonin adolescence ninth decade life will attenuate capacity night-time modulate effects early morning CAR. The interactions melatonin/BAG-1/Hsp90 proposed underpin how risk. This may differential melatonin/BAG-1/Hsp90/GR different cells microenvironments across body, tumors emerge. provides model pathogenesis better integrates previously disparate bodies data, including immune regulated tumor microenvironment, at least partly regulation tryptophan-melatonin pathway. has number future research treatment implications.

Language: Английский

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Polycystic Ovary Syndrome Pathophysiology: Integrating Systemic, CNS and Circadian Processes

Frontiers in Bioscience-Landmark, Journal Year: 2024, Volume and Issue: 29(1), P. 24 - 24

Published: Jan. 18, 2024

The conceptualization of polycystic ovary syndrome (PCOS) has primarily focused on hormonal alterations driven by changes within the hypothalamus and ovarian granulosa cells, with treatment contraceptive pill weight loss. However, a growing body data implicates wider systemic central nervous system (CNS) in pathoetiology pathophysiology PCOS, consequent implications for targeted treatments. It is proposed that there significant role night-time interactions factors acting to regulate whether rising level cortisol over night during morning awakening response (CAR) able induce nuclear translocation glucocorticoid receptor (GR), thereby influencing how immune glial systems cellular function preparation coming day. Factors affording protection PCOS also inhibit GR including gut microbiome-derived butyrate, pineal/local melatonin as well regulated bcl2-associated athanogene (BAG)-1. A pathophysiological attributed aryl hydrocarbon (AhR), which shows heightened levels activity PCOS. AhR activated ligands many processes, white adipocyte-derived kynurenine, implicating obesity occurring ovaries. activation consequences physiological hypothalamic paraventricular nucleus, cells adipocytes, partly mediated upregulation mitochondrial N-acetylserotonin/melatonin ratio, decreasing availability whilst increasing local stress plasticity nucleus. This article reviews detail CNS highlighting pineal melatonergic pathway, nucleus tanycytes/astrocytes, hypothalamus-pituitary-adrenal (HPA) axis pathophysiology. integrates wide array previously disparate biological underpinnings associates other currently classified medical conditions, such depression, bipolar disorder, type 1 diabetes mellitus autism spectrum. Numerous future research are detailed.

Language: Английский

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A More Holistic Perspective of Alzheimer's Disease: Roles of Gut Microbiome, Adipocytes, HPA Axis, Melatonergic Pathway and Astrocyte Mitochondria in the Emergence of Autoimmunity

Frontiers in Bioscience-Landmark, Journal Year: 2023, Volume and Issue: 28(12), P. 355 - 355

Published: Dec. 28, 2023

Alzheimer's disease is widely regarded as poorly treated due to poor conceptualization. For 40 years, pathophysiology has focused on two culprits, amyloid-β induced plaques and hyperphosphorylated tau associated tangles, with no significant treatment advance. This confounded by data showing be an endogenous antimicrobial that increased in a wide array of diverse medical conditions heightened inflammation. article reviews the wider bodies pertaining pathophysiology, highlighting role suppressed astrocyte mitochondrial function melatonergic pathway core hub driving neuronal loss dementia. It proposed over aging becomes dysregulated, at least partly mediated systemic processes involving 10-fold decrease pineal melatonin leading attenuated capacity night-time dampen residual daytime Suppressed also attenuates melatonin's inhibition glucocorticoid receptor nuclear translocation, thereby changing not only stress/hypothalamus-pituitary-adrenal (HPA) axis consequences but cortisol awakening response, which 'primes body for coming day'. Gut microbiome-derived butyrate inhibits well inducing pathway. prevents autocrine paracrine effects limiting levels effects. production induction lactate, decreasing metabolism The lactate melatonin, coupled suppression decreases mitophagy, major histocompatibility complex (MHC)-1. MHC-1 initiates chemoattraction CD8+ t cells, destruction being driven 'autoimmune'/'immune-mediated' processes. may therefore conceptualized initiated act astrocytes hub, leaving neurons deplete appropriate metabolic substrates co-ordinated antioxidants. culminates 'immune-mediated' cell death. Future research treatment/prevention implications are indicated.

Language: Английский

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Gut Microbiome and Circadian Interactions with Platelets Across Human Diseases, including Alzheimer’s Disease, Amyotrophic Lateral Sclerosis, and Cancer

Current Topics in Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 23(28), P. 2699 - 2719

Published: Oct. 9, 2023

Abstract: Platelets have traditionally been investigated for their role in clot formation the course of cardiovascular diseases and strokes. However, recent work indicates platelets to be an integral aspect wider systemic processes, with relevance pathophysiology a host diverse medical conditions, including neurodegenerative disorders cancer. This article reviews platelet function interactions gut microbiome circadian systems, highlighting mitochondrial melatonergic pathway determining activation, fluxes plasticity. provides number novel conceptualizations mode interaction other cell types, pathoetiology such as cancer, Alzheimer’s disease, amyotrophic lateral sclerosis. It is proposed that platelet-gut axis allows contribute many pathophysiological processes linked dysbiosis permeability. at least partly via sphingosine- 1-phosphate release, which regulates enteric glial cells lymphocyte chemotaxis, indicating etiological wide array conditions alterations microbiome. are also important regulator various microenvironments underpin most human tumor microenvironment, diseases, autoimmune disorders. Platelet serotonin release availability systemically, thereby being determinant dynamic metabolic occurring across types conditions. In addition, future research directions treatment implications proposed.

Language: Английский

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Neuroplasticity: Pathophysiology and Role in Major Depressive Disorder

Critical Reviews™ in Oncogenesis, Journal Year: 2024, Volume and Issue: 29(4), P. 19 - 32

Published: Jan. 1, 2024

Neuroplasticity is characterized by the brain's ability to change its activity in response extrinsic and intrinsic factors thought be mechanism behind all brain functions. causes structural functional changes on a molecular level, specifically growth of different regions synaptic post-synaptic activities. The four types neuroplasticity are homologous area adaption, compensatory masquerade, cross-modal reassignment, map expansion. All these help work around injuries or new information inputs. In addition baseline physical functions, basis emotional mental regulations impairment it can cause various illnesses. Concurrently, illnesses further damage plasticity brain. Major depressive disorder (MDD) one most common It affected accelerates neuroplasticity. chronically depressed state mind that impact patient's daily life, including life interests. This review will focus highlighting physiological aspects disease role pathogenesis pathology disorder. Moreover, monoamine regulation ketamine uptake discussed terms their antidepressant effects outcomes MDD.

Language: Английский

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