Attention-deficit/hyperactive disorder updates

Frontiers in Molecular Neuroscience, Journal Year: 2022, Volume and Issue: 15

Published: Sept. 21, 2022

Attention-deficit/hyperactive disorder (ADHD) is a neurodevelopmental that commonly occurs in children with prevalence ranging from 3.4 to 7.2%. It profoundly affects academic achievement, well-being, and social interactions. As result, this of high cost both individuals society. Despite the availability knowledge regarding mechanisms ADHD, pathogenesis not clear, hence, existence many challenges especially making correct early diagnosis provision accurate management.We aimed review pathogenic pathways ADHD children. The major focus was provide an update on reported etiologies humans, animal models, modulators, therapies, mechanisms, epigenetic changes, interaction between genetic environmental factors.References for were identified through systematic search PubMed by using special keywords all years until January 2022.Several genes have been associate ADHD: DRD1, DRD2, DRD4, DAT1, TPH2, HTR1A, HTR1B, SLC6A4, HTR2A, DBH, NET1, ADRA2A, ADRA2C, CHRNA4, CHRNA7, GAD1, GRM1, GRM5, GRM7, GRM8, TARBP1, ADGRL3, FGF1, MAOA, BDNF, SNAP25, STX1A, ATXN7, SORCS2. Some these evidence human beings while others either humans or models only. Notably, most are knockout do generate alteration patients. Besides, some gene polymorphisms differ according ethnic groups. majority available related dopaminergic pathway. Epigenetic changes including SUMOylation, methylation, acetylation pathway.The pathway remains be crucial ADHD. can affected factors other pathways. Nevertheless, it still unclear how relate neurotransmitter pathways; thus, more studies needed. Although several there few model genes, they More required.

Language: Английский

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A multiomic atlas of the aging hippocampus reveals molecular changes in response to environmental enrichment

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 16, 2024

Abstract Aging involves the deterioration of organismal function, leading to emergence multiple pathologies. Environmental stimuli, including lifestyle, can influence trajectory this process and may be used as tools in pursuit healthy aging. To evaluate role epigenetic mechanisms context, we have generated bulk tissue single cell multi-omic maps male mouse dorsal hippocampus young old animals exposed environmental stimulation form enriched environments. We present a molecular atlas aging process, highlighting two distinct axes, related inflammation dysregulation mRNA metabolism, at functional RNA protein level. Additionally, report alteration heterochromatin domains, loss bivalent chromatin uncovering heterochromatin-switch phenomenon whereby constitutive is partially mitigated through gains facultative heterochromatin. Notably, observed reversal great number aging-associated alterations context enrichment, which was particularly linked glial oligodendrocyte pathways. In conclusion, our work describes epigenomic landscape reveals how lifestyle intervention lead multi-layered decline.

Language: Английский

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The Development of the Mesoprefrontal Dopaminergic System in Health and Disease

Frontiers in Neural Circuits, Journal Year: 2021, Volume and Issue: 15

Published: Oct. 12, 2021

Midbrain dopaminergic neurons located in the substantia nigra and ventral tegmental area are main source of dopamine brain. They send out projections to a variety forebrain structures, including dorsal striatum, nucleus accumbens, prefrontal cortex (PFC), establishing nigrostriatal, mesolimbic, mesoprefrontal pathways, respectively. The input PFC is essential for performance higher cognitive functions such as working memory, attention, planning, decision making. gradual maturation these skills during postnatal development correlates with local circuits, which undergo lengthy functional remodeling process neonatal adolescence stage. During this period, innervation also matures: fibers rather sparse at prenatal stages slowly increase density finally reach stable pattern early adulthood. Despite prominent role regulation function, relatively little known about how established PFC, whether it influences circuits exactly facilitates PFC. In review, we provide an overview system rodents primates discuss altered signaling neuropsychiatric neurodevelopmental disorders.

Language: Английский

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Serotonergic and Adrenergic Neuroreceptor Manipulation Ameliorates Core Symptoms of ADHD through Modulating Dopaminergic Receptors in Spontaneously Hypertensive Rats

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2300 - 2300

Published: Feb. 15, 2024

The core symptoms of attention deficit hyperactivity disorder (ADHD) are due to the hypofunction brain’s adrenergic (NE) and dopamine (DA) systems. Drugs that enhance DA NE neurotransmission in brain by blocking their transporters or receptors current therapeutic strategies. Of late, emerging results point out serotonergic (5-HT) system, which indirectly modulates activity reducing ADHD. On this basis, second-generation antipsychotics, utilize 5-HT receptors, were prescribed children with However, it is not clear how modulate minimize present study investigates efficacy alpha-2 receptor manipulation tackling ADHD affects neuroreceptors regions involved Fifteen-day-old male spontaneously hypertensive rats (SHRs) received 5-HT1A agonist (ipsapirone) 5-HT2A antagonist (MDL 100907) (i.p.) (GFC) from postnatal days 15 42 along age-matched Wistar Kyoto (WKY) (n = 8 each group). ADHD-like behaviors assessed using a battery behavioral tests during 44 65. After tests, rat brains processed estimate density 5-HT1A, 5-HT2A, DA-D1, DA-D2 prefrontal cortex, striatum, substantia nigra. All three neuroreceptor manipulations able SHRs. positive effect was mainly associated upregulation all areas investigated, while cortex Further, DA-D1 expression downregulated except for agonists striatum antagonists upregulated In animal model study, monotherapies curtail differential different brain.

Language: Английский

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Saturated and unsaturated high-fat diets induce addictive-like behavior in an animal model of operant self-administration

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2025, Volume and Issue: unknown, P. 111295 - 111295

Published: Feb. 1, 2025

Language: Английский

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miRNA signatures associated with vulnerability to food addiction in mice and humans

Journal of Clinical Investigation, Journal Year: 2022, Volume and Issue: 132(10)

Published: March 29, 2022

Food addiction is characterized by a loss of behavioral control over food intake and associated with obesity other eating disorders. The mechanisms underlying this disorder are largely unknown. We aimed to investigate the changes in miRNA expression promoted animals humans their involvement hallmarks disorder. found sharp similitudes between signatures medial prefrontal cortex (mPFC) our animal cohort circulating levels human cohort, which allowed us identify several miRNAs potential interest development Tough decoy (TuD) inhibition miRNA-29c-3p mouse mPFC persistence response enhanced vulnerability developing addiction, whereas miRNA-665-3p compulsion-like behavior also vulnerability. In contrast, we that miRNA-137-3p did not lead addiction. Therefore, could be acting as protective factors regard believe elucidation these epigenetic will advances toward identifying innovative biomarkers possible future interventions for related disorders based on strategies now available modify activity expression.

Language: Английский

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Social Isolation Induces Changes in the Monoaminergic Signalling in the Rat Medial Prefrontal Cortex

Cells, Journal Year: 2024, Volume and Issue: 13(12), P. 1043 - 1043

Published: June 17, 2024

(1) Background: The effects of short-term social isolation during adulthood have not yet been fully established in rats behaviourally, and at all transcriptomically the medial prefrontal cortex (mPFC). (2) Methods: We measured behavioural housing adult male pairs or alone for 10 days. also used RNA sequencing to measure accompanying gene expression alterations mPFC rats. (3) Results: isolated animals exhibited reduced sociability novelty preference, but increased interaction. There was no change their aggression, anxiety, depression-like activity. Transcriptomic analysis revealed a differential 46 genes between groups. KEGG pathway showed that differentially expressed are involved neuroactive ligand-receptor interactions, particularly dopaminergic peptidergic systems, addiction. Subsequent validation confirmed decreased level three altered genes: regulator G protein signalling 9 (Rgs9), serotonin receptor 2c (Htr2c), Prodynorphin (Pdyn), which dopaminergic, serotonergic, function, respectively. Antagonizing Htr2c its role discrimination. (4) Conclusions: Social homeostatic regulations include monoaminergic systems mPFC.

Language: Английский

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Linking drug and food addiction: an overview of the shared neural circuits and behavioral phenotype

Frontiers in Behavioral Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Sept. 12, 2023

Despite a lack of agreement on its definition and inclusion as specific diagnosable disturbance, the food addiction construct is supported by several neurobiological behavioral clinical preclinical findings. Recognizing critical to understanding how why it manifests. In this overview, we focused those follows: 1. hyperpalatable effects in development; 2. brain regions involved both drug addiction; 3. animal models highlighting commonalities between substance use disorders addiction. Although results collected through studies emerged from protocols differing ways, they clearly highlight manifestations alterations characteristics. To develop improved models, heterogeneity should be acknowledged embraced so that research can systematically investigate role variables development different features addiction-like behavior models.

Language: Английский

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Breaking the Chains: Advances in Substance Addiction Research through Single-Cell Sequencing, Epigenetics, and Epitranscriptomic

Future Pharmacology, Journal Year: 2024, Volume and Issue: 4(1), P. 115 - 138

Published: Jan. 29, 2024

Addiction is a complex brain disease influenced by genetic, environmental, and neurological factors. Psychostimulants, cocaine, methamphetamine influence different cell types in regions, with focus on the neurons responsible for rewarding effects nucleus accumbens (NAc) ventral tegmental area (VTA). Known markers psychostimulant-induced neuronal plasticity combination droplet-based high-throughput single-cell sequencing divided heterogeneity of populations NAc VTA into clusters, where all cells same type do not respond equally to exposure psychostimulants. To explain as changes amplitude phase shifts gene expression, we focused epigenetic mechanisms DNA chromatin modifications, well accessibility. We also comment epitranscriptomics novel approach study messenger RNA posttranslational modification, which regulates translation potentially localized transcription synapses order address molecular chains that connect addiction from expression synaptic and, finally, plasticity.

Language: Английский

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Addiction neurobiologists should study resilience

Addiction Neuroscience, Journal Year: 2024, Volume and Issue: 11, P. 100152 - 100152

Published: March 5, 2024

The study of addiction has historically focused on identifying the differences which make susceptible individuals fall prey to drug use and abuse. This resulted in a deep understanding learning, reward, habit-formation circuits drive initial reinforcement, as well exploration cognitive control anxiety systems are important for craving relapse use. However, most human users smaller proportion laboratory animals resilient addiction, meaning that they can addictive drugs without developing substance disorders. Evidence from neurobiology resilience stress models suggests mechanisms distinct those vulnerability, thus may be missed if is not investigated. In this review, we briefly review limitations our knowledge have focus vulnerability. We next introduce formal construct its historical application clinical research. Finally, present evidence presence studies neuroscience argue an increase protective against By intentionally compensatory rather than only focusing susceptibility, more effective therapeutic approaches discovered.

Language: Английский

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