MicroRNA regulation of prefrontal cortex development and psychiatric risk in adolescence

Morgunova, Alice; Flores, Cecilia

doi:10.1016/j.semcdb.2021.04.011

Cited by 27 publications

(16 citation statements)

References 165 publications

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“…This work would eventually allow for preventive and therapeutic interventions precisely targeted in time. MicroRNAs, for example, show promise to serve as such markers, as they regulate guidance cue genes in adolescence and are detectable in peripheral fluids (Torres-Berrío et al, 2020b ; Morgunova and Flores, 2021 ). Finally, a critical question that remains open is whether and how “positive” experiences can promote healthy DA system development and improve mental health outcomes in emerging adults.…”

Section: Discussionmentioning

confidence: 99%

Mesocorticolimbic Dopamine Pathways Across Adolescence: Diversity in Development

Reynolds

Flores²

2021

Front. Neural Circuits

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Mesocorticolimbic dopamine circuity undergoes a protracted maturation during adolescent life. Stable adult levels of behavioral functioning in reward, motivational, and cognitive domains are established as these pathways are refined, however, their extended developmental window also leaves them vulnerable to perturbation by environmental factors. In this review, we highlight recent advances in understanding the mechanisms underlying dopamine pathway development in the adolescent brain, and how the environment influences these processes to establish or disrupt neurocircuit diversity. We further integrate these recent studies into the larger historical framework of anatomical and neurochemical changes occurring during adolescence in the mesocorticolimbic dopamine system. While dopamine neuron heterogeneity is increasingly appreciated at molecular, physiological, and anatomical levels, we suggest that a developmental facet may play a key role in establishing vulnerability or resilience to environmental stimuli and experience in distinct dopamine circuits, shifting the balance between healthy brain development and susceptibility to psychiatric disease.

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Section: Discussionmentioning

confidence: 99%

Mesocorticolimbic Dopamine Pathways Across Adolescence: Diversity in Development

Reynolds

Flores²

2021

Front. Neural Circuits

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“…This is a major health concern due to the potential adverse consequences on brain development, thus rendering the adolescent more vulnerable to addictive and psychopathological disorders (Spear, 2011). Moreover, stress and abuse of substances might exacerbate symptoms associated with psychiatric disorders such as schizophrenia (Thomas and Zakharenko, 2021) and depression (Morgunova and Flores, 2021). This is consistent with the high incidence of mental disorders is high during adolescence.…”

Section: Introductionmentioning

confidence: 82%

“…MicroRNAs are small ncRNAs that regulate messenger RNA (mRNA) translation by binding to the complementary mRNA sequence of target genes. This usually results in reduced gene expression by transcript degradation and/or prevention of mRNA translation, although increased mRNA translation has also been described (Rao and Pack, 2017;Morgunova and Flores, 2021). A single miRNA can bind to multiple mRNA targets resulting in the repression of hundreds of genes, including those coding enzymes involved in other epigenetic processes, as well as a single mRNA can be the target of multiple miRNAs.…”

Section: Introductionmentioning

confidence: 99%

“…The relevance of miRNAs mediating the environmental influence impact on neurodevelopment is suggested by clinical and preclinical studies. The available reviews focus on alcohol (Asimes et al, 2019;Zhu et al, 2022), nicotine and cocaine (Hayase, 2017), and stress related to psychiatric disorders risk (Morgunova and Flores, 2021). There is a recent review relating ncRNAs with the impact of prenatal stress, viral infections, and drugs, such as alcohol, nicotine, and anesthetics, during brain development (Leighton and Bredy, 2018;Arzua et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA Regulation of the Environmental Impact on Adolescent Neurobehavioral Development: A Systematic Review

Vázquez-Ágredos

Gámiz²,

Gallo³

2022

Front. Cell. Neurosci.

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Adolescence is a late developmental period marked by pronounced reorganization of brain networks in which epigenetic mechanisms play a fundamental role. This brain remodeling is associated with a peculiar behavior characterized by novelty seeking and risky activities such as alcohol and drug abuse, which is associated with increased susceptibility to stress. Hence, adolescence is a vulnerable postnatal period since short- and long-term deleterious effects of alcohol drinking and drug abuse are a serious worldwide public health concern. Among several other consequences, it has been proposed that exposure to stress, alcohol, or other drugs disrupts epigenetic mechanisms mediated by small non-coding microRNAs (miRNAs). During adolescence, this modifies the expression of a variety of genes involved in neurodevelopmental processes such as proliferation, differentiation, synaptogenesis, neural plasticity, and apoptosis. Hence, the effect of miRNAs dysregulation during adolescence might contribute to a long-term impact on brain function. This systematic review focuses on the miRNA expression patterns in the adolescent rodent brain with special interest in the impact of stress and drugs such as amphetamine, cocaine, nicotine, cannabis, and ketamine. The results point to a relevant and complex role of miRNAs in the regulation of the molecular processes involved in adolescent brain development as part of a dynamic epigenetic network sensitive to environmental events with distinctive changes across adolescence. Several miRNAs have been assessed evidencing changing expression profiles during the adolescent transition which are altered by exposure to stress and drug abuse. Since this is an emerging rapidly growing field, updating the present knowledge will contribute to improving our understanding of the epigenetic regulation mechanisms involved in the neurodevelopmental changes responsible for adolescent behavior. It can be expected that increased knowledge of the molecular mechanisms mediating the effect of environmental threats during the adolescent critical developmental period will improve understanding of psychiatric and addictive disorders emerging at this stage.

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“…While sensitive periods in sensory systems often occur during very early postnatal development [3][4][5] , we found that adolescence is a sensitive period for mPFC development. Adolescence is known to be a period of vulnerability in the development of psychiatric disorders such as schizophrenia in humans [11][12][13]53 . Moreover, functional imaging studies have shown that thalamo-prefrontal hypoconnectivity, a nding in patients with schizophrenia, is already present in young adolescents at clinical high risk for the disorder 15,18−23 .…”

Section: Adolescence Is a Key Period Of Cortical Maturationmentioning

confidence: 99%

Adolescent thalamic inhibition leads to long-lasting impairments in prefrontal cortex function

Benoit

Holt

Posani

et al. 2021

Preprint

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Impaired cortical maturation is a postulated mechanism in the etiology of neurodevelopmental disorders, including schizophrenia. In sensory cortex, activity relayed by the thalamus during a postnatal sensitive period is essential for proper cortical maturation. Whether thalamic activity also shapes prefrontal cortical maturation is unknown. Here, we show that inhibiting the midline thalamus during adolescence leads to a long-lasting decrease in thalamo-prefrontal projection density and cortical excitation. Adolescent thalamic inhibition also causes prefrontal-dependent cognitive deficits during adulthood that are associated with disrupted prefrontal cross-correlations and task outcome encoding. In contrast, thalamic inhibition during adulthood has no long-lasting consequences. Strikingly, exciting the thalamus in adulthood during a cognitive task rescues prefrontal cross-correlations, task outcome encoding, and cognitive deficits. These data point to adolescence as a sensitive window of thalamo-cortical circuit maturation. Furthermore, by supporting prefrontal network activity, boosting thalamic activity provides a potential therapeutic strategy for rescuing cognitive deficits in neurodevelopmental disorders.

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MicroRNA regulation of prefrontal cortex development and psychiatric risk in adolescence

Cited by 27 publications

References 165 publications

Mesocorticolimbic Dopamine Pathways Across Adolescence: Diversity in Development

Mesocorticolimbic Dopamine Pathways Across Adolescence: Diversity in Development

MicroRNA Regulation of the Environmental Impact on Adolescent Neurobehavioral Development: A Systematic Review

Adolescent thalamic inhibition leads to long-lasting impairments in prefrontal cortex function

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