Mitochondria and the central nervous system: searching for a pathophysiological basis of psychiatric disorders

Streck, Emílio L.; Gonçalves, Cinara L.; Furlanetto, Camila B.; Scaini, Giselli; Dal‐Pizzol, Felipe; Quevedo, João

doi:10.1590/1516-4446-2013-1224

Cited by 74 publications

(54 citation statements)

References 177 publications

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“…challenges (32) and contribute to the development of psychopathologies (9,10,13,14). Therefore, our results highlight differences in mitochondrial function in the NAc as a potential mechanism underlying the susceptibility or resilience to develop depression, and may open new prospects for the advancement of preventive therapeutic approaches to mood disorders.…”

Section: Discussionmentioning

confidence: 66%

“…Recent work has highlighted the potential for individual differences in mitochondrial function and, more broadly, energy metabolism to influence vulnerability to develop psychopathological disorders, such as anxiety and depression (9)(10)(11)(12)(13)(14). Here, we demonstrate that trait anxiety is a determining factor of social rank that is mediated by brain regionspecific mitochondrial function.…”

mentioning

confidence: 53%

“…Furthermore, mitochondrial deficiency is frequently observed in brain disorders (55), including depression (13,14,26,31,56) and anxiety (9). Moreover, individuals with mitochondrial disorders often express symptoms of depression and anxiety (10)(11)(12)(13). High anxiety trait is a known vulnerability factor to develop depression, particularly if individuals are exposed to stress (57,58), with stress impinging energetically costly neuronal adaptations (59,60).…”

Section: Discussionmentioning

confidence: 99%

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Mitochondrial function in the brain links anxiety with social subordination

Hollis

Kooij

Zanoletti

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

213

257

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Dominance hierarchies are integral aspects of social groups, yet whether personality traits may predispose individuals to a particular rank remains unclear. Here we show that trait anxiety directly influences social dominance in male outbred rats and identify an important mediating role for mitochondrial function in the nucleus accumbens. High-anxious animals that are prone to become subordinate during a social encounter with a low-anxious rat exhibit reduced mitochondrial complex I and II proteins and respiratory capacity as well as decreased ATP and increased ROS production in the nucleus accumbens. A causal link for these findings is indicated by pharmacological approaches. In a dyadic contest between anxietymatched animals, microinfusion of specific mitochondrial complex I or II inhibitors into the nucleus accumbens reduced social rank, mimicking the low probability to become dominant observed in highanxious animals. Conversely, intraaccumbal infusion of nicotinamide, an amide form of vitamin B3 known to enhance brain energy metabolism, prevented the development of a subordinate status in high-anxious individuals. We conclude that mitochondrial function in the nucleus accumbens is crucial for social hierarchy establishment and is critically involved in the low social competitiveness associated with high anxiety. Our findings highlight a key role for brain energy metabolism in social behavior and point to mitochondrial function in the nucleus accumbens as a potential marker and avenue of treatment for anxiety-related social disorders.anxiety | mitochondria | nucleus accumbens | social dominance | social competition

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Section: Discussionmentioning

confidence: 66%

mentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

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Mitochondrial function in the brain links anxiety with social subordination

Hollis

Kooij

Zanoletti

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

213

257

View full text Add to dashboard Cite

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“…Por un lado, se descartan a los seres humanos con características genéticas no deseadas y, por otro, se mejoran las características genéticas de las personas, perdiendo su identidad. Si bien se modifica un porcentaje pequeño de la información genética, existe una importante conexión entre el ADN nuclear y el ADN mitocondrial que no solo se interviene en la función bioenérgetica de las mitocondrias en el funcionamiento celular, sino que se describe más frecuentemente la contribución mitocondrial a la capacidad de neuroplasticidad y al desarrollo de la personalidad (43,44).…”

Section: Gestación Deliberada De Embriones Humanos Como Materials Biteunclassified

Valoración ética de las nuevas opciones reproductivas en las enfermedades mitocondriales

Moya

2016

Acta bioeth.

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Resumen: Las enfermedades mitocondriales son un grupo de desórdenes clínicamente heterogéneo con manifestaciones clínicas muy variables y alta tasa de morbi-mortalidad. Tienen complejas implicancias en la reproducción, ya que los riesgos de repetición en la familia son variables, 25% en las formas autosómicas recesivas, alrededor de 4% en los casos de mutaciones mitocondriales de novo, y un riesgo incierto pero elevado si la madre es portadora de las mutaciones mitocondriales. Por ello, se proponen distintas técnicas de diagnóstico preimplantacional, prenatal o de reproducción asistida a fin de evitar el nacimiento de niños con esta patología. En el presente trabajo se describen y analizan las implicancias científicas y éticas de las nuevas técnicas de reproducción asistida que se proponen a las familias con alto riesgo.Palabras clave: enfermedades mitocondriales, reproducción asistida, trasplante mitocondrial, dignidad humana Ethical value of new reproductive choices in mitochondrial diseasesAbstract: Mitochondrial diseases are a clinically heterogeneous group of disorders with variable clinical features and high morbidity and mortality. As there are different hereditary patterns, complex implications in reproduction are expected; the recurrence risk may be about 25% in autosomal recessive inheritance, 4% in de novo mitochondrial mutations, and an uncertain, but high risk, when the mother is carrier of mitochondrial mutations. Thus, different preimplantation and prenatal diagnosis or assisted reproductive techniques are proposed to avoid the birth of children with these diseases. In this paper scientific and ethical implications of new assisted reproductive techniques offer to high risk families are describe and analyzed. Key words: mitochondrial disorders, assisted reproductive techniques, mitochondrial transplant, human dignity Valoração ética das novas opções reprodutivas nas enfermidades mitocondriaisResumo: As enfermidades mitocondriais são um grupo de desordens clinicamente heterogêneos com manifestações clínicas muito variáveis e alta taxa de morbi-mortalidade. Têm complexas implicações na reprodução, já que os riscos de repetição na família são variáveis, 25% nas formas autossômicas recessivas, ao redor de 4% nos casos de mutações mitocondriais de novo, e um risco incerto porém elevado se a mãe é portadora das mutações mitocondriais. Por isso, se propõem distintas técnicas de diagnóstico pré-implantacional, pré-natal ou de reprodução assistida a fim de evitar o nascimento de crianças com esta patologia. No presente trabalho se descrevem e analisam as implicações científicas e éticas das novas técnicas de reprodução assistida que se propõem às famílias com alto risco.Palavras-chave: enfermidades mitocondriais, reprodução assistida, transplante mitocondrial, dignidade humana

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“…Recently, it has been proposed that apart from a deficiency of monoamine transmission, neuroendocrine changes and a dysregulation of the immune system, depression, bipolar disorder and anxiety disorders may be associated with mitochondrial dysfunction (Gardner and Boles, 2011;Streck et al, 2014;Tobe, 2013). It is widely recognized that mitochondria play a pivotal role in cellular energy metabolism by generation of ATP -a source of chemical energy.…”

Section: Introductionmentioning

confidence: 99%