Paternal nicotine exposure induces hyperactivity in next-generation via down-regulating the expression of DAT

Zhang, Meixing; Zhang, Dong; Dai, Jingbo; Cao, Yunxia; Xu, Wangjie; He, Guang; Wang, Zhaoxia; Wang, Lianyu; R, Li; Qiao, Zhongdong

doi:10.1016/j.tox.2020.152367

Cited by 22 publications

(8 citation statements)

References 43 publications

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“…Consistent with previous work [29, 57], this study found that PNE induced significant impairments in object-based attention. While mTBI did not exacerbate the attention deficits in the PNE mice, the repetitive injury did result in a transient impairment of attention in the non-PNE control mice.…”

Section: Discussionsupporting

confidence: 92%

Repetitive Mild Traumatic Brain Injury in a Perinatal Nicotine Exposure Mouse Model of Attention Deficit Hyperactivity Disorder

et al. 2021

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Attention deficit hyperactivity disorder (ADHD) increases the risk for concussion or mild traumatic brain injury (mTBI). At the same time, recommendations for the management of ADHD include participation in sports and other organized physical activities, including those that carry an increased risk of mTBI. Very little work has been done to determine the extent to which untreated ADHD adversely impacts behavioral outcomes of repeated mild concussions. Here, we used a perinatal nicotine exposure (PNE) mouse model of ADHD combined with a closed-head, repetitive mTBI model. The PNE mouse model carries significant construct, face, and predictive validity as a preclinical model of ADHD. Two-month-old PNE and control mice were subjected to closed-head repetitive mTBI or sham procedure once daily for 5 days. Object-based attention, novel object recognition memory, spatial working memory, and depression-like behavior were analyzed 1 day and 2 weeks following repeated mTBI. Consistent with our previous reports, mice in the PNE group showed significant deficits in object-based attention and working memory prior to mTBI. These deficits persisted following the repeated mTBI. Repeated mTBI produced a transient attention deficit in the control group but did not exacerbate the attention deficit that is characteristic of the PNE group. Although neither PNE nor repetitive mTBI alone influenced immobility in the tail suspension test, when PNE mice were subjected to mTBI, there was a transient increase in this measurement suggesting a synergistic effect of ADHD and mTBI on depression-like behavior. Thus, our data using the PNE mouse model suggest that ADHD may be a risk factor for transient depression following repeated mTBI and that repeated mTBI may be a risk factor for transient attention deficit.

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Section: Discussionsupporting

confidence: 92%

Repetitive Mild Traumatic Brain Injury in a Perinatal Nicotine Exposure Mouse Model of Attention Deficit Hyperactivity Disorder

et al. 2021

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“…DAT1 gene 5′-UTR methylation has been suggested as a new approach for the exploration of an epigenetic biomarker in ADHD diagnosis. Paternal nicotine exposure prompts hyperactivity in C57BL/6 mice next-generation through down-regulating the expression of DAT which results from hyper-methylation of DAT ( Zhang et al, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

Attention-deficit/hyperactive disorder updates

Kessi

Duan

Xiong

et al. 2022

Front. Mol. Neurosci.

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

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“…Several studies have found abnormalities in DNA methylation associated with ADHD. Zhang et al [ 22 ] exposed male C57BL/6 mice to 2mg/kg of nicotine for 5 weeks and then mated them with wild-type females (Table 1 ). The offspring of male mice were subjected to behavioral tests at 8 weeks after birth.…”

Section: Role Of Dna Methylation In the Pathogenesis Of Attention Def...mentioning

confidence: 99%

The Role of Epigenetics in the Pathogenesis and Potential Treatment of Attention Deficit Hyperactivity Disorder

Peedicayil

2022

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: There is increasing evidence that dsyregulated epigenetic mechanisms of gene expression are involved in the pathogenesis of attention deficit hyperactivity disorder (ADHD). This review presents a comprehensive summary of the current state of research on the role of epigenetics in the pathogenesis of ADHD. The potential role of epigenetic drugs in the treatment of ADHD is also reviewed. Several studies suggest there are epigenetic abnormalities in preclinical models of ADHD and in ADHD patients. Regarding DNA methylation many studies have reported DNA hypermethylation. There is evidence that there is increased histone deacetylation in ADHD patients. Abnormalities in the expression of microRNAs (miRNAs) in ADHD patients have also been found. Some currently used drugs for treating ADHD, in addition to their more well established mechanisms of action, have been shown to alter epigenetic mechanisms of gene expression. Clinical trials of epigenetic drugs in patients with ADHD are reporting favorable results. These data suggest that abnormal epigenetic mechanisms of gene expression may be involved in the pathogenesis of ADHD. Drugs acting on epigenetic mechanisms may be a potential new class of drugs for treating ADHD.

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Paternal nicotine exposure induces hyperactivity in next-generation via down-regulating the expression of DAT

Cited by 22 publications

References 43 publications

Repetitive Mild Traumatic Brain Injury in a Perinatal Nicotine Exposure Mouse Model of Attention Deficit Hyperactivity Disorder

Repetitive Mild Traumatic Brain Injury in a Perinatal Nicotine Exposure Mouse Model of Attention Deficit Hyperactivity Disorder

Attention-deficit/hyperactive disorder updates

The Role of Epigenetics in the Pathogenesis and Potential Treatment of Attention Deficit Hyperactivity Disorder

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