Journal of neurogenetics最新文献

{"title":"Dopaminergic gene analysis indicates influence of inattention but not IQ in executive dysfunction of Indian ADHD probands","authors":"S. Maitra, M. Chatterjee, S. Sinha, K. Mukhopadhyay","doi":"10.1080/01677063.2019.1672679","DOIUrl":"https://doi.org/10.1080/01677063.2019.1672679","url":null,"abstract":"Abstract Organizational inefficiency and inattention are speculated to be the reason for executive deficit (ED) of ADHD probands. Even with average IQ, probands often perform poorly due to higher inattention. Pharmacotherapy, cognitive behavioural therapy, and counselling provide only symptomatic relief. Several candidate genes showed involvement with ADHD; the most consistent are dopamine receptor 4 (DRD4) and solute carrier family 6 member 3 (SLC6A3). We analyzed association of rarely investigated DRD4 and SLC6A3 variants with ADHD core traits in Indo-Caucasoid probands. ED, inattention, organizational efficiency, and IQ were measured by Barkley Deficit in Executive Functioning-Child & Adolescent scale, DSM-IV-TR, Conners’ Parent Rating Scale-revised, and WISC respectively. Target sites were analyzed by PCR, RFLP, and/or Sanger sequencing of genomic DNA. DRD4 variants mostly affected inattention while SLC6A3 variants showed association with IQ. Few DRD4 and SLC6A3 variants showed dichotomous association with IQ and inattention. DRD4 Exon3 VNTR >4R showed negative impact on all traits excepting IQ. Inattention showed correlation with attention span, organizational efficiency, and ED, while IQ failed to do so. We infer that IQ and attention could be differentially regulated by dopaminergic gene variants affecting functional efficiency in ADHD and the two traits should be considered together for providing better rehabilitation.","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"33 1","pages":"209 - 217"},"PeriodicalIF":1.9,"publicationDate":"2019-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01677063.2019.1672679","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43901862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heritable natural variation of light/dark preference in an outbred zebrafish population","authors":"Amelia D. Dahlén, Mahendra Wagle, M. Zarei, Su Guo","doi":"10.1080/01677063.2019.1663846","DOIUrl":"https://doi.org/10.1080/01677063.2019.1663846","url":null,"abstract":"Abstract Anxiety is a fear-like response to stimuli perceived to be threatening. Excessive or uncontrollable anxiety is a debilitating psychiatric disorder which affects many people throughout their lifetime. In unravelling the complex genetic and environmental regulations of anxiety-like phenotypes, models measuring the natural dark avoidance of larval zebrafish have shed light on the individual variation and heritability of this anxiety-related trait. Using the light/dark choice paradigm and selective breeding, this study aims to validate previous findings of the variable (VDA) and strong dark aversion (SDA) heritability in AB-WT larval zebrafish using the outbred zebrafish strain EK, which offers more genetic diversity to aid in future molecular mapping efforts. 190 larvae (6 days post fertilization [dpf] and 7 dpf) were tested across four trials and divided into variable (VDA), medium (MDA) and strong (SDA) dark aversion for further in-crosses. VDA and MDA larvae became more explorative with time, whereas SDA larvae rarely left the preferred light zone. The SDA and VDA in-crosses significantly increased the respective phenotypes in the second generation of larvae, whereas VDA × MDA inter-crosses did not. For the second-generation SDA cohort, dark aversion correlated with increased thigmotaxis, which reinforces SDA as an anxiety-like phenotype. Our finding that the dark aversion trait and SDA and VDA phenotypes are heritable in an outbred zebrafish population lays an important foundation for future studies of genetic underpinnings using whole-genome mapping methods. This conserved fear/anxiety-like response in a highly accessible model organism also allows for further pharmacological and behavioral studies to elucidate the etiology of anxiety and the search for novel therapeutics for anxiety disorders.","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"33 1","pages":"199 - 208"},"PeriodicalIF":1.9,"publicationDate":"2019-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01677063.2019.1663846","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42773639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Milk-whey diet substantially suppresses seizure-like phenotypes of <i>para^Shu</i>, a <i>Drosophila</i> voltage-gated sodium channel mutant.","authors":"Junko Kasuya,&nbsp;Atulya Iyengar,&nbsp;Hung-Lin Chen,&nbsp;Patrick Lansdon,&nbsp;Chun-Fang Wu,&nbsp;Toshihiro Kitamoto","doi":"10.1080/01677063.2019.1597082","DOIUrl":"https://doi.org/10.1080/01677063.2019.1597082","url":null,"abstract":"<p><p>The <i>Drosophila</i> mutant <i>para^Shu</i> harbors a dominant, gain-of-function allele of the voltage-gated sodium channel gene, <i>paralytic</i> (<i>para</i>). The mutant flies display severe seizure-like phenotypes, including neuronal hyperexcitability, spontaneous spasms, ether-induced leg shaking, and heat-induced convulsions. We unexpectedly found that two distinct food recipes used routinely in the <i>Drosophila</i> research community result in a striking difference in severity of the <i>para^Shu</i> phenotypes. Namely, when <i>para^Shu</i> mutants were raised on the diet originally formulated by Edward Lewis in 1960, they showed severe neurological defects as previously reported. In contrast, when they were raised on the diet developed by Frankel and Brousseau in 1968, these phenotypes were substantially suppressed. Comparison of the effects of these two well-established food recipes revealed that the diet-dependent phenotypic suppression is accounted for by milk whey, which is present only in the latter. Inclusion of milk whey in the diet during larval stages was critical for suppression of the adult <i>para^Shu</i> phenotypes, suggesting that this dietary modification affects development of the nervous system. We also found that milk whey has selective effects on other neurological mutants. Among the behavioral phenotypes of different <i>para</i> mutant alleles, those of <i>para^GEFS+</i> and <i>para^bss</i> were suppressed by milk whey, while those of <i>para^DS</i> and <i>para^ts1</i> were not significantly affected. Overall, our study demonstrates that different diets routinely used in <i>Drosophila</i> labs could have considerably different effects on neurological phenotypes of <i>Drosophila</i> mutants. This finding provides a solid foundation for further investigation into how dietary modifications affect development and function of the nervous system and, ultimately, how they influence behavior.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"33 3","pages":"164-178"},"PeriodicalIF":1.9,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01677063.2019.1597082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37244997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Axon length maintenance and synapse integrity are regulated by c-AMP-dependent protein kinase A (PKA) during larval growth of the drosophila sensory neurons.","authors":"Tijana Copf,&nbsp;Mildred Kamara,&nbsp;Tadmiri Venkatesh","doi":"10.1080/01677063.2019.1586896","DOIUrl":"https://doi.org/10.1080/01677063.2019.1586896","url":null,"abstract":"<p><p>Axonal extension and synaptic targeting are usually completed during early development, but the axonal length and synaptic integrity need to be actively maintained during later developmental stages and the adult life. Failure in the axonal length maintenance and the subsequent axonal degeneration have been associated with neurological disorders, but currently little is known about the genetic factors controlling this process. Here, we show that regulated intracellular levels of cAMP-dependent protein kinase A (PKA) are critical for the axon maintenance during the transition from the early to the later larval stages in the Drosophila class IV dendritic arborization (da) sensory neurons. Our data indicate that when the intracellular levels of PKA are increased via genetic manipulations, these peripheral neurons initially form synapses with wild-type appearance, at their predicted ventral nerve cord (VNC) target sites (in the first and second instar larval stages), but that their synapses disintegrate, and the axons retract and become fragmented in the subsequent larval stages (third larval stage). The affected axonal endings at the disintegrated synaptic sites still express the characteristic presynaptic and cytoskeletal markers such as Bruchpilot and Fascin, indicating that the synapse had been initially properly formed, but that it later lost its integrity. Finally, the phenotype is significantly more prominent in the axons of the neurons whose cell bodies are located in the posterior body segments. We propose that the reason for this is the fact that during the larval development the posterior neurons face a much greater challenge while trying to keep up with the fast-paced growth of the larval body, and that PKA is critical for this process. Our data reveal PKA as a novel factor in the axonal length and synapse integrity maintenance in sensory neurons. These results could be of help in understanding neurological disorders characterized by destabilized synapses.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"33 3","pages":"157-163"},"PeriodicalIF":1.9,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01677063.2019.1586896","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37126622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Continuous tracking of startled <i>Drosophila</i> as an alternative to the negative geotaxis climbing assay.","authors":"Matthew J Taylor,&nbsp;Richard I Tuxworth","doi":"10.1080/01677063.2019.1634065","DOIUrl":"https://doi.org/10.1080/01677063.2019.1634065","url":null,"abstract":"<p><p>The fruit fly, <i>Drosophila,</i> is commonly used to study late-onset neurodegenerative diseases due to the combination of powerful genetic tools, cheap and simple husbandry and short lifespan. One widely-used measure of disease progression is the age-dependent decline in motor performance that manifests in most <i>Drosophila</i> neurodegeneration models. This is usually quantified using a simple climbing assay. However, the standard climbing assay lacks sensitivity and suffers from high variability meaning large numbers of flies are needed or bespoke apparatus and software solutions. Here, we present a modification of the open-source, MATLAB-based, DART software to measure the decline in \"startle response\" with age. We demonstrate that the DART setup is more sensitive to the motor performance decline induced by adult-onset neuronal expression of amyloid beta (Aβ) peptides than a traditional climbing assay despite using smaller cohorts of flies. DART also has the potential to generate multiple metrics of motor behaviour during the startle response. The software requires no coding skills to operate and the required apparatus can be purchased commercially. Therefore, DART is a more useful method than the climbing assay for longitudinal assays of motor performance and will enable higher-throughput screen for genetic and pharmacological modifiers of neurodegeneration. In our proof-of-concept screen for modifiers of Aβ-dependent phenotypes, we identified that <i>in vivo</i> knock-down of <i>p53</i> in adult neurons is neuroprotective. This supports recent work targeting <i>p53 in vitro</i> and demonstrates the potential for DART to be used to screen for targets that ameliorate neurodegeneration.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"33 3","pages":"190-198"},"PeriodicalIF":1.9,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01677063.2019.1634065","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37404333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tango knock-ins visualize endogenous activity of G protein-coupled receptors in Drosophila.","authors":"Hidetaka Katow,&nbsp;Takahiro Takahashi,&nbsp;Kuniaki Saito,&nbsp;Hiromu Tanimoto,&nbsp;Shu Kondo","doi":"10.1080/01677063.2019.1611806","DOIUrl":"https://doi.org/10.1080/01677063.2019.1611806","url":null,"abstract":"<p><p>G protein-coupled receptors (GPCRs) represent a family of seven-pass transmembrane protein receptors whose ligands include neuropeptides and small-molecule neuromodulators such as dopamine and serotonin. These neurotransmitters act at long distances and are proposed to define the ground state of the nervous system. The <i>Drosophila</i> genome encodes approximately 50 neuropeptides and their functions in physiology and behavior are now under intensive studies. Key information currently lacking in the field is the spatiotemporal activation patterns of endogenous GPCRs. Here we report application of the Tango system, a reporter assay to detect GPCR activity, to endogenous GPCRs in the fly genome. We developed a method to integrate the sensor component of the Tango system to the C-terminus of endogenous genes by using genome editing techniques. We demonstrate that Tango sensors in the <i>Sex-peptide receptor</i> (<i>SPR</i>) locus allow sensitive detection of mating-dependent SPR activity in the female reproductive organ. The method is easily applicable to any GPCR and will provide a way to systematically characterize GPCRs in the fly brain.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"33 2","pages":"44-51"},"PeriodicalIF":1.9,"publicationDate":"2019-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01677063.2019.1611806","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37234262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The utility of whole exome sequencing in diagnosing neurological disorders in adults from a highly consanguineous population.","authors":"Weiyi Mu,&nbsp;Nicoline Schiess,&nbsp;Jennifer L Orthmann-Murphy,&nbsp;Ayman W El-Hattab","doi":"10.1080/01677063.2018.1555249","DOIUrl":"https://doi.org/10.1080/01677063.2018.1555249","url":null,"abstract":"<p><p>There is increasing evidence that whole exome sequencing (WES) has a high diagnostic yield and is cost-efficient for individuals with neurological phenotypes. However, there is limited data on the use of WES in non-Western populations, including populations with a high rate of consanguinity. Retrospective chart review was performed on 24 adults with undiagnosed neurological symptoms evaluated in genetics and neurology clinics in a tertiary care facility on the Arabian Peninsula, and had WES between 2014 and 2016. Definitive diagnoses were made in 13/24 (54%) of cases. Of these, 5/13 (38%) revealed novel pathogenic variants. Of the known 19/24 (79%) consanguineous cases, diagnostic rate was slightly higher, 11/19 (58%) as compared to 2/5 (40%) among non-consanguineous cases. Autosomal recessive disorders comprised 10/13 (77%) of molecular diagnoses, all found to be due to homozygous pathogenic variants among consanguineous cases. WES in this cohort of adults with neurological symptoms had a high diagnostic rate likely due to high consanguinity rates in this population, as evidenced by the high diagnostic rate of homozygous pathogenic variants.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"33 1","pages":"21-26"},"PeriodicalIF":1.9,"publicationDate":"2019-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01677063.2018.1555249","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36980638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative behavioral genetics: the Yamamoto approach.","authors":"Hiromu Tanimoto,&nbsp;Chun-Fang Wu","doi":"10.1080/01677063.2019.1616720","DOIUrl":"https://doi.org/10.1080/01677063.2019.1616720","url":null,"abstract":"","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"33 2","pages":"41-43"},"PeriodicalIF":1.9,"publicationDate":"2019-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01677063.2019.1616720","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37289220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Courtship behavior induced by appetitive olfactory memory.","authors":"Yuya Onodera,&nbsp;Rino Ichikawa,&nbsp;Kanta Terao,&nbsp;Hiromu Tanimoto,&nbsp;Nobuhiro Yamagata","doi":"10.1080/01677063.2019.1593978","DOIUrl":"https://doi.org/10.1080/01677063.2019.1593978","url":null,"abstract":"<p><p>Reinforcement signals such as food reward and noxious punishment can change diverse behaviors. This holds true in fruit flies, <i>Drosophila melanogaster</i>, which can be conditioned by an odor and sugar reward or electric shock punishment. Despite a wide variety of behavior modulated by learning, conditioned responses have been traditionally measured by altered odor preference in a choice, and other memory-guided behaviors have been only scarcely investigated. Here, we analyzed detailed conditioned odor responses of flies after sugar associative learning by employing a video recording and semi-automated processing pipeline. Trajectory analyses revealed that multiple behavioral components were altered along with conditioned approach to the rewarded odor. Notably, we found that lateral wing extension, a hallmark of courtship behavior of <i>D. melanogaster</i>, was robustly increased specifically in the presence of the rewarded odor. Strikingly, genetic disruption of the mushroom body output did not impair conditioned courtship increase, while markedly weakening conditioned odor approach. Our results highlight the complexity of conditioned responses and their distinct regulatory mechanisms that may underlie coordinated yet complex memory-guided behaviors in flies.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"33 2","pages":"143-151"},"PeriodicalIF":1.9,"publicationDate":"2019-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01677063.2019.1593978","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37128638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinctions among electroconvulsion- and proconvulsant-induced seizure discharges and native motor patterns during flight and grooming: quantitative spike pattern analysis in <i>Drosophila</i> flight muscles.","authors":"Jisue Lee,&nbsp;Atulya Iyengar,&nbsp;Chun-Fang Wu","doi":"10.1080/01677063.2019.1581188","DOIUrl":"https://doi.org/10.1080/01677063.2019.1581188","url":null,"abstract":"<p><p>In <i>Drosophila</i>, high-frequency electrical stimulation across the brain triggers a highly stereotypic repertoire of spasms. These electroconvulsive seizures (ECS) manifest as distinctive spiking discharges across the nervous system and can be stably assessed throughout the seizure repertoire in the large indirect flight muscles dorsal longitudinal muscles (DLMs) to characterize modifications in seizure-prone mutants. However, the relationships between ECS-spike patterns and native motor programs, including flight and grooming, are not known and their similarities and distinctions remain to be characterized. We employed quantitative spike pattern analyses for the three motor patterns including: (1) overall firing frequency, (2) spike timing between contralateral fibers, and (3) short-term variability in spike interval regularity (CV₂) and instantaneous firing frequency (ISI^-1). This base-line information from wild-type (WT) flies facilitated quantitative characterization of mutational effects of major neurotransmitter systems: excitatory cholinergic (<i>Cha</i>), inhibitory GABAergic (<i>Rdl</i>) and electrical (<i>ShakB</i>) synaptic transmission. The results provide an initial glimpse on the vulnerability of individual motor patterns to different perturbations. We found marked alterations of ECS discharge spike patterns in terms of either seizure threshold, spike frequency or spiking regularity. In contrast, no gross alterations during grooming and a small but noticeable reduction of firing frequency during <i>Rdl</i> mutant flight were found, suggesting a role for GABAergic modulation of flight motor programs. Picrotoxin (PTX), a known pro-convulsant that inhibits GABA_A receptors, induced DLM spike patterns that displayed some features, e.g. left-right coordination and ISI^-1 range, that could be found in flight or grooming, but distinct from ECS discharges. These quantitative techniques may be employed to reveal overlooked relationships among aberrant motor patterns as well as their links to native motor programs.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"33 2","pages":"125-142"},"PeriodicalIF":1.9,"publicationDate":"2019-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01677063.2019.1581188","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37149192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}