keyword
https://read.qxmd.com/read/37987120/leaky-lessons-learned-efflux-prone-dopamine-transporter-variant-dat-val559-reveals-sex-and-circuit-specific-contributions-of-d2-receptor-signaling-to-neuropsychiatric-disease
#21
REVIEW
Felix P Mayer, Adele Stewart, Randy D Blakely
Aberrant dopamine (DA) signaling has been implicated in various neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), schizophrenia, bipolar disorder (BPD) and addiction. The availability of extracellular DA is sculpted by exocytotic release of vesicular DA and subsequent transporter-mediated clearance, rendering the presynaptic DA transporter (DAT) a crucial regulator of DA neurotransmission. D2-type DA autoreceptors (D2ARs) regulate multiple aspects of DA homeostasis, including i) DA synthesis, ii) vesicular release, iii) DA neuron firing, and iv), the surface expression of DAT and DAT- mediated DA clearance...
November 21, 2023: Basic & Clinical Pharmacology & Toxicology
https://read.qxmd.com/read/37957291/the-effects-of-methylphenidate-and-atomoxetine-on-drosophila-brain-at-single-cell-resolution-and-potential-drug-repurposing-for-adhd-treatment
#22
JOURNAL ARTICLE
Susu Qu, Xiangyu Zhou, Zhicheng Wang, Yi Wei, Han Zhou, Xinshuang Zhang, Qingjie Zhu, Yanmin Wang, Quanjun Yang, Likun Jiang, Yuan Ma, Yuan Gao, Lei Kong, Li Zhang
The stimulant methylphenidate (MPH) and the non-stimulant atomoxetine (ATX) are frequently used for the treatment of attention-deficit/hyperactivity disorder (ADHD); however, the function of these drugs in different types of brain cells and their effects on related genes remain largely unknown. To address these questions, we built a pipeline for the simultaneous examination of the activity behavior and transcriptional responses of Drosophila melanogaster at single-cell resolution following drug treatment. We selected the Drosophila with significantly increased locomotor activities (hyperactivity-like behavior) following the administration of each drug in comparison with the control (same food as the drug-treated groups with 5% sucrose, yeast, and blue food dye solution) using EasyFlyTracker...
November 13, 2023: Molecular Psychiatry
https://read.qxmd.com/read/37952603/a-new-mechanistic-insight-into-the-association-between-environmental-perfluorooctane-sulfonic-acid-pfos-exposure-and-attention-deficit-and-hyperactivity-disorder-adhd-like-behavior
#23
JOURNAL ARTICLE
Miao Zhang, Xueyan Gu, Liu Wu, Nannan Wan, Yu Liu, Zaijun Xin, Tianbing Chen, Shuai Liu, Mingqi Li, Mi Deng, Qiyu Wang
Perfluorooctane sulfonic acid (PFOS) is one of the main residual environmental pollutants that threaten human health. PFOS exposure is positively correlated with the prevalence of attention deficit hyperactivity disorder (ADHD); however, the underlying mechanism is unknown. Given that dopamine (DA) is a crucial target for PFOS and that its dysfunction is a key role in ADHD development, it is speculated that PFOS exposure contributes to the occurrence of ADHD to some extent by disrupting DA homeostasis. To establish the relationship between PFOS exposure, DA dysfunction, and ADHD-like behavior, adult zebrafish were exposed to PFOS for 21 days using PFOS concentrations in the serum of patients with ADHD as the reference exposure dose...
December 2023: Neurotoxicology
https://read.qxmd.com/read/37942650/bh4-as-a-therapeutic-target-for-adhd-relevance-to-neurotransmitters-and-stress-driven-symptoms
#24
JOURNAL ARTICLE
Samson K Wilson, Jaya Thomas
Tetrahydrobiopterin (BH4) is a critical cofactor in a variety of metabolic pathways that have been linked to ADHD. There have been no previous studies utilizing BH4 as a supplement for ADHD. BH4 has been approved as a treatment for phenylketonuria (PKU). Individuals with PKU and ADHD appear to have low DA levels in common, suggesting that the hypodopaminergic state seen in both illnesses could be a relationship between the two. Clinical research involving supplementation of BH4 has shown low occurrence of adverse...
November 9, 2023: Journal of Attention Disorders
https://read.qxmd.com/read/37865339/the-effects-of-phenylalanine-and-tyrosine-levels-on-dopamine-production-in-rat-pc12%C3%A2-cells-implications-for-treatment-of-phenylketonuria-tyrosinemia-type-1-and-comorbid-neurodevelopmental-disorders
#25
JOURNAL ARTICLE
Peter D Szigetvari, Sudarshan Patil, Even Birkeland, Rune Kleppe, Jan Haavik
Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene, resulting in phenylalanine accumulation and impaired tyrosine production. In Tyrosinemia type 1 (TYRSN1) mutations affect fumarylacetoacetate hydrolase, leading to accumulation of toxic intermediates of tyrosine catabolism. Treatment of TYRSN1 with nitisinone results in extreme tissue levels of tyrosine. Although PKU and TYRSN1 have opposite effects on tyrosine levels, both conditions have been associated with neuro-psychiatric symptoms typically present in ADHD, possibly indicating an impaired dopamine (DA) synthesis...
October 19, 2023: Neurochemistry International
https://read.qxmd.com/read/37843488/an-updated-safety-review-of-the-current-drugs-for-managing-adhd-in-children
#26
REVIEW
Erika Ryst, Ann Childress
INTRODUCTION: Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly prevalent condition that causes persistent problems with attention and/or hyperactivity-impulsivity and often results in significant impairment when left untreated. Medications for this disorder continue to evolve and provide new treatment options. Ongoing review of related medication safety and tolerability remains an important task for prescribers. AREAS COVERED: This manuscript provides an updated safety review of medications used to treat ADHD in children and adolescents...
October 16, 2023: Expert Opinion on Drug Safety
https://read.qxmd.com/read/37761006/characterization-of-behavioral-phenotypes-in-heterozygous-dat-rat-based-on-pedigree
#27
JOURNAL ARTICLE
Gioia Zanfino, Concetto Puzzo, Vincenzo de Laurenzi, Walter Adriani
Dopamine is an essential neurotransmitter whose key roles include movement control, pleasure and reward, attentional and cognitive skills, and regulation of the sleep/wake cycle. Reuptake is carried out by the dopamine transporter (DAT; DAT1 SLC6A3 gene). In order to study the effects of hyper-dopaminergia syndrome, the gene was silenced in rats. DAT-KO rats show stereotypical behavior, hyperactivity, a deficit in working memory, and an altered circadian cycle. In addition to KO rats, heterozygous (DAT-HET) rats show relative hypofunction of DAT; exact phenotypic effects are still unknown and may depend on whether the sire or the dam was KO...
September 18, 2023: Biomedicines
https://read.qxmd.com/read/37760987/-dat1-5-un-translated-region-methylation-patterns-as-bio-markers-of-adhd-psycho-pathology-contribution-to-disease-prognosis-and-to-monitoring-of-a-successful-therapy
#28
JOURNAL ARTICLE
Valentina Carpentieri, Silvia Cugno, Katarina Lockic, Esterina Pascale, Walter Adriani
Epigenetic modifications, such as changes in DNA methylation, have been linked to several diseases in recent years. The purpose of our study was to search for biomarkers that (using non-invasive techniques) could assist the clinician in the prognosis of infant/adolescent psychopathology. We previously showed that changes in methylation of the 5'-UTR in the DAT1/SLC6A3 gene can be used as a biomarker for the prognosis of initial severe ADHD: treatment-resistant severe ADHD children were characterized by methylated CpG 1 in particular, while methylated CpGs 2 and 6 were then found in children who improved after the therapy...
September 15, 2023: Biomedicines
https://read.qxmd.com/read/37745438/developmental-pyrethroid-exposure-disrupts-molecular-pathways-for-circadian-rhythms-and-synaptic-plasticity-in-mouse-brain
#29
Jennifer H Nguyen, Melissa A Curtis, Ali S Imami, William G Ryan, Khaled Alganem, Kari L Neifer, Nilanjana Saferin, Charlotte N Nawor, Brian P Kistler, Gary W Miller, Rammohan Shukla, Robert E McCullumsmith, James P Burkett
Neurodevelopmental disorders (NDDs) are a category of pervasive disorders of the developing nervous system with few or no recognized biomarkers. A significant portion of the risk for NDDs, including attention deficit hyperactivity disorder (ADHD), is contributed by the environment, and exposure to pyrethroid pesticides during pregnancy has been identified as a potential risk factor for NDD in the unborn child. We recently showed that low-dose developmental exposure to the pyrethroid pesticide deltamethrin in mice causes male-biased changes to ADHD- and NDD-relevant behaviors as well as the striatal dopamine system...
September 13, 2023: bioRxiv
https://read.qxmd.com/read/37740887/attention-deficit-hyperactivity-disorder-and-inflammation-natural-product-derived-treatments-a-review-of-the-last-ten-years
#30
REVIEW
Alexandre Martins, Magali Conte, Márcia Inês Goettert, Verônica Contini
OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) is a psychiatric disorder characterized by symptoms of inattention, hyperactivity, and impulsivity. Stimulant medication is the main pharmacological treatment for ADHD. However, the traditional pharmacological treatments may have significant side effects; therefore, non-pharmacological approaches are needed. Thus, there has been growing interest in alternative herbal treatments. The aim of this review was to comprehensively assess the current evidence for plant-based treatment of ADHD in human and animal models, as well as their ability to modulate the inflammatory process...
September 23, 2023: Inflammopharmacology
https://read.qxmd.com/read/37740715/dopaminergic-cell-protection-and-alleviation-of-neuropsychiatric-disease-symptoms-by-vmat2-expression-through-the-class-i-hdac-inhibitor-tc-h-106
#31
JOURNAL ARTICLE
Heejin Lee, Hye-Ji Kim, Dong-Kyu Choi, Eu N-A Ko, Jae-Hyeog Choi, Yohan Seo, Sion Lee, Soong-Hyun Kim, Sejin Jung, Minwoo Kim, Dongwan Kang, Chun-Young Im, Gi-Hun Bae, Sung-Cherl Jung, Oh-Bin Kwon
The importance of vesicular monoamine transporter 2 (VMAT2) in dopamine regulation, which is considered crucial for neuropsychiatric disorders, is currently being studied. Moreover, the development of disease treatments using histone deacetylase (HDAC) inhibitors (HDACi) is actively progressing in various fields. Recently, research on the possibility of regulating neuropsychiatric disorders has been conducted. In this study, we evaluated whether VMAT2 expression increased by an HDACi can fine-tune neuropsychotic behavior, such as attention deficit hyperactivity disorder (ADHD) and protect against the cell toxicity through oxidized dopamine...
October 2023: Pharmacology Research & Perspectives
https://read.qxmd.com/read/37725477/the-atypical-dopamine-transporter-inhibitor-ce-158-enhances-dopamine-neurotransmission-in-the-prefrontal-cortex-of-male-rats-a-behavioral-electrophysiological-and-microdialysis-study
#32
JOURNAL ARTICLE
Claudia Sagheddu, Enzo Cancedda, Farshid Bagheri, Predrag Kalaba, Anna Lisa Muntoni, Jana Lubec, Gert Lubec, Fabrizio Sanna, Marco Pistis
BACKGROUND: Dopamine plays a key role in several physiological functions such as motor control, learning and memory, motivation and reward. The atypical dopamine transporter inhibitor CE-158 has been recently reported to promote behavioral flexibility and restore learning and memory in aged rats. METHODS: Adult male rats were intraperitoneally administered for 1 or 10 days with CE-158 at the dose of 1 or 10 mg/kg, and tested for extracellular dopamine in the medial prefrontal cortex (mPFC) by means of intracerebral microdialysis and single unit cell recording in the same brain area...
September 19, 2023: International Journal of Neuropsychopharmacology
https://read.qxmd.com/read/37710339/the-mesocortical-dopaminergic-system-cannot-explain-hyperactivity-in-an-animal-model-of-attention-deficit-hyperactivity-disorder-adhd-spontaneously-hypertensive-rats-shr
#33
JOURNAL ARTICLE
Aysegul Gungor Aydin, Esat Adiguzel
BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent neuropsychiatric disorders with morphological brain abnormalities. There is a growing body of evidence that abnormalities in the dopaminergic system may account for ADHD pathogenesis. However, it is not clear whether the dopaminergic system is hyper or hypoactive. To determine whether the DA neurons and/or axons deficiency might be the cause of the postulated dopaminergic hypofunction in spontaneously hypertensive rats (SHR, animal model of ADHD), this study examined the dopaminergic neurons and fibers in the brain tissues of SHRs and Wistar Kyoto rats (WKY, control animals)...
September 14, 2023: Laboratory Animal Research
https://read.qxmd.com/read/37658396/ocular-and-neural-genes-jointly-regulate-the-visuospatial-working-memory-in-adhd-children
#34
JOURNAL ARTICLE
Yilu Zhao, Yuanxin Zhong, Wei Chen, Suhua Chang, Qingjiu Cao, Yufeng Wang, Li Yang
OBJECTIVE: Working memory (WM) deficits have frequently been linked to attention deficit hyperactivity disorder (ADHD). Despite previous studies suggested its high heritability, its genetic basis, especially in ADHD, remains unclear. The current study aimed to comprehensively explore the genetic basis of visual-spatial working memory (VSWM) in ADHD using wide-ranging genetic analyses. METHODS: The current study recruited a cohort consisted of 802 ADHD individuals, all met DSM-IV ADHD diagnostic criteria...
September 1, 2023: Behavioral and Brain Functions: BBF
https://read.qxmd.com/read/37607442/high-fat-diet-induced-dopaminergic-dysregulation-induces-rem-sleep-fragmentation-and-adhd-like-behaviors
#35
JOURNAL ARTICLE
Jiseung Kang, Mincheol Park, Chang-Myung Oh, Tae Kim
Consumption of a high-fat diet (HFD) has been associated with reduced wakefulness and various behavioral deficits, including anxiety, depression, and anhedonia. The dopaminergic system, which plays a crucial role in sleep and ADHD, is known to be vulnerable to chronic HFD. However, the association between HFD-induced behavioral and molecular changes remains unclear. Therefore, we investigated the effects of a HFD on the dopaminergic system and its association with behavioral deficits in male mice. The mice were divided into normal diet and HFD groups and were analyzed for sleep patterns, behavior tests, and transcription levels of dopamine-related genes in the brain...
August 12, 2023: Psychiatry Research
https://read.qxmd.com/read/37606043/cry1%C3%AE-11-mutation-induces-adhd-like-symptoms-through-hyperactive-dopamine-d1-receptor-signaling
#36
JOURNAL ARTICLE
Dengfeng Liu, Zhengyu Xie, Panyang Gu, Xiangyu Li, Yichun Zhang, Xinying Wang, Zhiheng Chen, Suixin Deng, Yousheng Shu, Jia-Da Li
Attention-deficit hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder that affects approximately 5.3% of children and approximately 2.5% of adults. There is an intimate relationship between ADHD and sleep disturbance. Specifically, individuals carry a mutation in the core circadian gene CRY1 (c. 1657 + 3A > C), which results in the deletion of exon 11 expression in the CRY1 protein (CRY1Δ11), causing them to exhibit typical ADHD symptoms. However, the underlying mechanism is still elusive...
August 22, 2023: JCI Insight
https://read.qxmd.com/read/37603143/daytime-impulsiveness-attention-and-learning-in-the-restless-legs-syndrome
#37
JOURNAL ARTICLE
Inci Sule Ozer, Ece Bayram, Oguzhan Herdi, Huseyin Ozden Sener
INTRODUCTION: Restless legs syndrome (RLS) is a sensorimotor condition characterized by disturbing sensations and the desire to move, often localized in the legs. Cognitive changes and impulsivity can be present in RLS, although the potential effect of commonly co-occurring attention-deficit/hyperactivity disorders (ADHD) or dopamine agonist (DA) use on these are unclear. METHOD: Twenty-three RLS patients and 22 healthy controls were included. Rey Auditory Verbal Learning Test (RAVLT), Continuous Performance Test (CPT), Beck Depression Inventory (BDI), Epworth Sleepiness Scale (ESS), State and Trait Anxiety Inventory (STAI), and Adult Attention Deficit Self-Evaluation Scale (ASRS) were administered...
August 21, 2023: Neurological Sciences
https://read.qxmd.com/read/37561236/sex-differences-in-long-term-outcome-of-prenatal-exposure-to-excess-glucocorticoids-implications-for-development-of-psychiatric-disorders
#38
JOURNAL ARTICLE
Frederik Elberling, Stefan Spulber, Raj Bose, Hoi Yee Keung, Virpi Ahola, Zongli Zheng, Sandra Ceccatelli
Exposure to prenatal insults, such as excess glucocorticoids (GC), may lead to pathological outcomes, including neuropsychiatric disorders. The aim of the present study was to investigate the long-term effects of in utero exposure to the synthetic GC analog dexamethasone (Dex) in adult female offspring. We monitored spontaneous activity in the home cage under a constant 12 h/12 h light/dark cycle, as well as the changes following a 6-h advance of dark onset (phase shift). For comparison, we re-analysed data previously recorded in males...
August 10, 2023: Molecular Neurobiology
https://read.qxmd.com/read/37560458/metheamphetamine-for-children-are-we-over-or-under-dosing
#39
JOURNAL ARTICLE
Kenneth Blum, Catherine Dennen, Paul R Carney, Elizabeth Gilley, Panayotis K Thanos, Eric R Braverman, David Baron, Colin Hanna, Edward J Modestino, Mark S Gold, Igor Elman, Rajendra D Badgaiyan
An estimated 3% to 10% of school children meet the DSM-V criteria for ADHD (Attention-Deficit/Hyperactivity Disorder), however, to be over-diagnosed, the rate of children inappropriately diagnosed with ADHD (false positives) would have to be larger than the number of children with ADHD who are under-identified and not diagnosed (false negatives). Accordingly, a number of investigators take the position that under-treatment with psychostimulants, especially in children and adolescence, will result in continued ADHD symptomatology including future Substance Use Disorder (SUD)...
April 22, 2023: J Addict Psychiatry
https://read.qxmd.com/read/37503220/developmental-manganese-exposure-causes-lasting-attention-deficits-accompanied-by-dysregulation-of-mtor-signaling-and-catecholaminergic-gene-expression-in-brain-prefrontal-cortex
#40
N A Santiago, B He, S L Howard, S Beaudin, B J Strupp, D R Smith
UNLABELLED: Elevated manganese (Mn) exposure is associated with attentional deficits in children, and is an environmental risk factor for attention deficit hyperactivity disorder (ADHD). We have shown that developmental Mn exposure causes lasting attention and sensorimotor deficits in a rat model of early childhood Mn exposure, and that these deficits are associated with a hypofunctioning catecholaminergic system in the prefrontal cortex (PFC), though the mechanistic basis for these deficits is not well understood...
July 18, 2023: bioRxiv
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