The role of mitochondria in cocaine addiction

2021 ◽  
Vol 478 (4) ◽  
pp. 749-764
Author(s):  
Claire Thornton ◽  
Etty Grad ◽  
Rami Yaka
Keyword(s):  
Mitochondrial Dynamics ◽  
Brain Regions ◽  
Cocaine Exposure ◽  
Transport Chain ◽  
Metabolic Gene Expression ◽  
Mitochondrial Functions ◽  
The Impact ◽  
The Brain ◽  
And Oxidative Stress

The incidence of cocaine abuse is increasing especially in the U.K. where the rates are among the highest in Europe. In addition to its role as a psychostimulant, cocaine has profound effect on brain metabolism, impacting glycolysis and impairing oxidative phosphorylation. Cocaine exposure alters metabolic gene expression and protein networks in brain regions including the prefrontal cortex, the ventral tegmental area and the nucleus accumbens, the principal nuclei of the brain reward system. Here, we focus on how cocaine impacts mitochondrial function, in particular through alterations in electron transport chain function, reactive oxygen species (ROS) production and oxidative stress (OS), mitochondrial dynamics and mitophagy. Finally, we describe the impact of cocaine on brain energy metabolism in the developing brain following prenatal exposure. The plethora of mitochondrial functions altered following cocaine exposure suggest that therapies maintaining mitochondrial functional integrity may hold promise in mitigating cocaine pathology and addiction.

The Brain in a Physician’s Life

2017 ◽  
Author(s):  
Peggy Mason
Keyword(s):  
Nervous System ◽  
Brain Regions ◽  
Altered State ◽  
Compassionate Care ◽  
Clinical Impairment ◽  
Altered State Of Consciousness ◽  
Individual Nature ◽  
The Impact ◽  
The Brain

With the knowledge acquired from this book, the brain regions responsible for each of the symptoms suffered by Jean-Dominique Bauby can be identified. It is also possible to understand why thought, language, and memory were unaffected in Bauby. Bauby’s narrative is used to launch a consideration of the role of embodiment in affective experience. The experience of Clive Wearing who, after a bout of encephalitis, was left without the ability to make new declarative memories is introduced to illustrate the highly personal and individual nature of people’s reactions to disease or clinical impairment. The impact of disease does not stop with the patient but extends to the patient’s loved ones and caregivers. This is particularly true of patients with dementia or those in an altered state of consciousness. Finally the reader is encouraged to use their understanding of the nervous system to provide compassionate care for patients.

scholarly journals Does COVID-19 Affect Adult Neurogenesis? A Neurochemical Perspective

2021 ◽  
Author(s):  
Jayakumar Saikarthik ◽  
Ilango Saraswathi ◽  
Abdulrahman A. Al-Atram
Keyword(s):  
Adult Neurogenesis ◽  
Cell Activation ◽  
Immune Cell ◽  
Neuropsychiatric Symptoms ◽  
Brain Regions ◽  
Immune Cell Activation ◽  
Brain Involvement ◽  
The Impact ◽  
The Brain

COVID-19 has been found to cause neuropsychiatric symptoms which indicate brain involvement. SARS-CoV-2 may enter the brain by damaging and penetrating olfactory mucosa and via other possible routes like damaged blood–brain barrier, and hematologic spread. With SARS-CoV-2 having a higher affinity to ACE2 receptors, brain regions that have higher ACE2 receptors like the hippocampus, are more vulnerable to the effect of the viral invasion. In addition, immune cell activation, an important feature of COVID-19, leads to cytokine storm which causes neurotoxicity, neuroinflammation, and neurodegeneration. Impaired adult neurogenesis is related to many psychiatric disorders including depression, bipolar disorder, anxiety disorder, schizophrenia, and PTSD. It is known to be related to the depletion of neurotransmitters, dopamine, serotonin, norepinephrine, GABA, and glutamate which play a major role in adult neurogenesis. A recent study reveals that SSRI which acts by increasing serotonin is proven beneficial in COVID-19 patients. Thus, the current chapter will discuss the impact of COVID-19 on adult neurogenesis with emphasis on the role of ACE2 and neurotransmitters.

scholarly journals Role of Mitochondria in Viral Infections

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 232
Author(s):  
Srikanth Elesela ◽  
Nicholas W. Lukacs
Keyword(s):  
Viral Infections ◽  
Mitochondrial Dynamics ◽  
The Body ◽  
Viral Diseases ◽  
Multiple Organs ◽  
Innate Immune Signaling ◽  
Mitochondrial Functions ◽  
Host Virus Interactions ◽  
Virus Interactions

Viral diseases account for an increasing proportion of deaths worldwide. Viruses maneuver host cell machinery in an attempt to subvert the intracellular environment favorable for their replication. The mitochondrial network is highly susceptible to physiological and environmental insults, including viral infections. Viruses affect mitochondrial functions and impact mitochondrial metabolism, and innate immune signaling. Resurgence of host-virus interactions in recent literature emphasizes the key role of mitochondria and host metabolism on viral life processes. Mitochondrial dysfunction leads to damage of mitochondria that generate toxic compounds, importantly mitochondrial DNA, inducing systemic toxicity, leading to damage of multiple organs in the body. Mitochondrial dynamics and mitophagy are essential for the maintenance of mitochondrial quality control and homeostasis. Therefore, metabolic antagonists may be essential to gain a better understanding of viral diseases and develop effective antiviral therapeutics. This review briefly discusses how viruses exploit mitochondrial dynamics for virus proliferation and induce associated diseases.

scholarly journals Power Failure of Mitochondria and Oxidative Stress in Neurodegeneration and Its Computational Models

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 229
Author(s):  
JunHyuk Woo ◽  
Hyesun Cho ◽  
YunHee Seol ◽  
Soon Ho Kim ◽  
Chanhyeok Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Computational Models ◽  
Neuronal Damage ◽  
Living Organism ◽  
The Body ◽  
Mitochondrial Functions ◽  
A Cell ◽  
The Brain ◽  
And Oxidative Stress

The brain needs more energy than other organs in the body. Mitochondria are the generator of vital power in the living organism. Not only do mitochondria sense signals from the outside of a cell, but they also orchestrate the cascade of subcellular events by supplying adenosine-5′-triphosphate (ATP), the biochemical energy. It is known that impaired mitochondrial function and oxidative stress contribute or lead to neuronal damage and degeneration of the brain. This mini-review focuses on addressing how mitochondrial dysfunction and oxidative stress are associated with the pathogenesis of neurodegenerative disorders including Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and Parkinson’s disease. In addition, we discuss state-of-the-art computational models of mitochondrial functions in relation to oxidative stress and neurodegeneration. Together, a better understanding of brain disease-specific mitochondrial dysfunction and oxidative stress can pave the way to developing antioxidant therapeutic strategies to ameliorate neuronal activity and prevent neurodegeneration.

scholarly journals Developmental cannabidiol exposure increases anxiety and modifies genome-wide brain DNA methylation in adult female mice

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Nicole M. Wanner ◽  
Mathia Colwell ◽  
Chelsea Drown ◽  
Christopher Faulk
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Coat Color ◽  
Brain Regions ◽  
Functional Enrichment ◽  
Positive Effects ◽  
Genome Wide ◽  
Nulliparous Female ◽  
The Impact ◽  
The Brain

Abstract Background Use of cannabidiol (CBD), the primary non-psychoactive compound found in cannabis, has recently risen dramatically, while relatively little is known about the underlying molecular mechanisms of its effects. Previous work indicates that direct CBD exposure strongly impacts the brain, with anxiolytic, antidepressant, antipsychotic, and other effects being observed in animal and human studies. The epigenome, particularly DNA methylation, is responsive to environmental input and can direct persistent patterns of gene regulation impacting phenotype. Epigenetic perturbation is particularly impactful during embryogenesis, when exogenous exposures can disrupt critical resetting of epigenetic marks and impart phenotypic effects lasting into adulthood. The impact of prenatal CBD exposure has not been evaluated; however, studies using the psychomimetic cannabinoid Δ9-tetrahydrocannabinol (THC) have identified detrimental effects on psychological outcomes in developmentally exposed adult offspring. We hypothesized that developmental CBD exposure would have similar negative effects on behavior mediated in part by the epigenome. Nulliparous female wild-type Agouti viable yellow (Avy) mice were exposed to 20 mg/kg CBD or vehicle daily from two weeks prior to mating through gestation and lactation. Coat color shifts, a readout of DNA methylation at the Agouti locus in this strain, were measured in F1 Avy/a offspring. Young adult F1 a/a offspring were then subjected to tests of working spatial memory and anxiety/compulsive behavior. Reduced-representation bisulfite sequencing was performed on both F0 and F1 cerebral cortex and F1 hippocampus to identify genome-wide changes in DNA methylation for direct and developmental exposure, respectively. Results F1 offspring exposed to CBD during development exhibited increased anxiety and improved memory behavior in a sex-specific manner. Further, while no significant coat color shift was observed in Avy/a offspring, thousands of differentially methylated loci (DMLs) were identified in both brain regions with functional enrichment for neurogenesis, substance use phenotypes, and other psychologically relevant terms. Conclusions These findings demonstrate for the first time that despite positive effects of direct exposure, developmental CBD is associated with mixed behavioral outcomes and perturbation of the brain epigenome.

Preserving Integrity in the Face of Performance Threat

2012 ◽  
Vol 23 (12) ◽  
pp. 1455-1460 ◽  
Author(s):  
Lisa Legault ◽  
Timour Al-Khindi ◽  
Michael Inzlicht
Keyword(s):  
Error Detection ◽  
Error Monitoring ◽  
Error Related Negativity ◽  
Threatening Information ◽  
Electrophysiological Responses ◽  
The Face ◽  
And Performance ◽  
The Impact ◽  
The Brain

Self-affirmation produces large effects: Even a simple reminder of one’s core values reduces defensiveness against threatening information. But how, exactly, does self-affirmation work? We explored this question by examining the impact of self-affirmation on neurophysiological responses to threatening events. We hypothesized that because self-affirmation increases openness to threat and enhances approachability of unfavorable feedback, it should augment attention and emotional receptivity to performance errors. We further hypothesized that this augmentation could be assessed directly, at the level of the brain. We measured self-affirmed and nonaffirmed participants’ electrophysiological responses to making errors on a task. As we anticipated, self-affirmation elicited greater error responsiveness than did nonaffirmation, as indexed by the error-related negativity, a neural signal of error monitoring. Self-affirmed participants also performed better on the task than did nonaffirmed participants. We offer novel brain evidence that self-affirmation increases openness to threat and discuss the role of error detection in the link between self-affirmation and performance.

scholarly journals Research participants as collaborators: Background, experience and policies from the PREVENT Dementia and EPAD programmes

Dementia ◽  
2018 ◽  
Vol 17 (8) ◽  
pp. 1045-1054 ◽  
Author(s):  
Sarah Gregory ◽  
Katie Wells ◽  
Kate Forsyth ◽  
Cate Latto ◽  
Helen Szyra ◽  
...  
Keyword(s):  
Patient Involvement ◽  
Research Participant ◽  
Steering Committee ◽  
Research Participants ◽  
Prospective Cohort Studies ◽  
Participant Experience ◽  
The Impact ◽  
The Brain ◽  
Public And Patient Involvement

Aim Despite the growing importance of public and patient involvement in biomedical research, comparatively little attention has been paid to the important role of research participants themselves. Our aim in this paper is to explore the impact research participant involvement has within the PREVENT and the European Prevention of Alzheimer’s Dementia (EPAD) projects. Method In this paper, we report the experiences of involving research participants as collaborators in prospective cohort studies exploring early changes in the brain as pathways towards and risks for dementia. We use minutes and feedback from members of the panel and steering committee to understand the experience and impact on the study. Results We describe the aims and structure of the participant panel established within the PREVENT Dementia study and highlight its contributions to the organisation, conduct and future of the study. Key areas of contribution identified include recruitment, inclusion of additional sub-studies, understanding the participant experience and contributing to the future of the study. Discussion We then describe how the PREVENT Dementia panel forms the basis for participant involvement within EPAD project.

scholarly journals Is There a Link between Oropharyngeal Microbiome and Schizophrenia? A Narrative Review

2022 ◽  
Vol 23 (2) ◽  
pp. 846
Author(s):  
Stanislas Martin ◽  
Audrey Foulon ◽  
Wissam El Hage ◽  
Diane Dufour-Rainfray ◽  
Frédéric Denis
Keyword(s):  
Periodontal Disease ◽  
Research Team ◽  
Oral Microbiome ◽  
Oral Microbiota ◽  
Future Studies ◽  
The Subject ◽  
The Moment ◽  
The Impact ◽  
The Brain

The study aimed to examine the impact of the oropharyngeal microbiome in the pathophysiology of schizophrenia and to clarify whether there might be a bidirectional link between the oral microbiota and the brain in a context of dysbiosis-related neuroinflammation. We selected nine articles including three systemic reviews with several articles from the same research team. Different themes emerged, which we grouped into 5 distinct parts concerning the oropharyngeal phageome, the oropharyngeal microbiome, the salivary microbiome and periodontal disease potentially associated with schizophrenia, and the impact of drugs on the microbiome and schizophrenia. We pointed out the presence of phageoma in patients suffering from schizophrenia and that periodontal disease reinforces the role of inflammation in the pathophysiology of schizophrenia. Moreover, saliva could be an interesting substrate to characterize the different stages of schizophrenia. However, the few studies we have on the subject are limited in scope, and some of them are the work of a single team. At this stage of knowledge, it is difficult to conclude on the existence of a bidirectional link between the brain and the oral microbiome. Future studies on the subject will clarify these questions that for the moment remain unresolved.

scholarly journals A selective effect of dopamine on information-seeking

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Valentina Vellani ◽  
Lianne P de Vries ◽  
Anne Gaule ◽  
Tali Sharot
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Information Seeking ◽  
Selective Effect ◽  
Reward Seeking ◽  
The Impact ◽  
The Brain ◽  
Insight Into ◽  
Primary Reward

Humans are motivated to seek information from their environment. How the brain motivates this behavior is unknown. One speculation is that the brain employs neuromodulatory systems implicated in primary reward-seeking, in particular dopamine, to instruct information-seeking. However, there has been no causal test for the role of dopamine in information-seeking. Here, we show that administration of a drug that enhances dopamine function (dihydroxy-L-phenylalanine; L-DOPA) reduces the impact of valence on information-seeking. Specifically, while participants under Placebo sought more information about potential gains than losses, under L-DOPA this difference was not observed. The results provide new insight into the neurobiology of information-seeking and generates the prediction that abnormal dopaminergic function (such as in Parkinson’s disease) will result in valence-dependent changes to information-seeking.

scholarly journals Mitochondrial genome and its regulator TFAM modulates head and neck tumourigenesis through intracellular metabolic reprogramming and activation of oncogenic effectors

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Yi-Ta Hsieh ◽  
Hsi-Feng Tu ◽  
Muh-Hwa Yang ◽  
Yi-Fen Chen ◽  
Xiang-Yun Lan ◽  
...  
Keyword(s):  
Head And Neck ◽  
Tongue Cancer ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Cellular Level ◽  
Metabolic Reprogramming ◽  
Transport Chain ◽  
Genetically Manipulated ◽  
The Impact

AbstractMitochondrial transcriptional factor A (TFAM) acts as a key regulatory to control mitochondrial DNA (mtDNA); the impact of TFAM and mtDNA in modulating carcinogenesis is controversial. Current study aims to define TFAM mediated regulations in head and neck cancer (HNC). Multifaceted analyses in HNC cells genetically manipulated for TFAM were performed. Clinical associations of TFAM and mtDNA encoded Electron Transport Chain (ETC) genes in regulating HNC tumourigenesis were also examined in HNC specimens. At cellular level, TFAM silencing led to an enhanced cell growth, motility and chemoresistance whereas enforced TFAM expression significantly reversed these phenotypic changes. These TFAM mediated cellular changes resulted from (1) metabolic reprogramming by directing metabolism towards aerobic glycolysis, based on the detection of less respiratory capacity in accompany with greater lactate production; and/or (2) enhanced ERK1/2-Akt-mTORC-S6 signalling activity in response to TFAM induced mtDNA perturbance. Clinical impacts of TFAM and mtDNA were further defined in carcinogen-induced mouse tongue cancer and clinical human HNC tissues; as the results showed that TFAM and mtDNA expression were significantly dropped in tumour compared with their normal counterparts and negatively correlated with disease progression. Collectively, our data uncovered a tumour-suppressing role of TFAM and mtDNA in determining HNC oncogenicity and potentially paved the way for development of TFAM/mtDNA based scheme for HNC diagnosis.

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