Pubmed du 18/06/16

Pubmed du jour

2016-06-18 12:03:50

1. {{Autism variants can influence behavior, communication traits in general population: Study suggests that trait variation can lend insight into etiology of neurodevelopmental, psychiatric disorders}}. {Am J Med Genet A}. 2016; 170(7): 1660-1.

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2. Cadette JN, Wilson CL, Brady MP, Dukes C, Bennett KD. {{The Effectiveness of Direct Instruction in Teaching Students with Autism Spectrum Disorder to Answer « Wh- » Questions}}. {J Autism Dev Disord}. 2016.

Research on the effects of Direct Instruction (DI) among students with Autism Spectrum Disorder (ASD) has only recently emerged. A benefit of DI is that it can be implemented with groups of students, which makes it potentially a cost effective method of instruction for some skills. In this study, we examined the effects of DI on teaching secondary students with ASD to answer three « wh- » questions. Using a multiple probe design across behaviors, results indicated the participants mastered two of the three « wh- » question types and made progress with the remaining question type. These results are discussed along with implications for educators instructing students with ASD.

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3. Cashin A. {{Autism Spectrum Disorder and Psychosis: A Case Study}}. {J Child Adolesc Psychiatr Nurs}. 2016.

PROBLEM: While apparently relatively common, there is often little clinician awareness of the risk of psychosis for people with autism. METHODS: A comprehensive review of the peer-reviewed literature and a presentation of a case study. FINDINGS: There is a paucity of research available to determine the prevalence of the experience of psychosis in people with autism. CONCLUSION: There is significant boundary overlap between autism spectrum disorder and schizophrenia spectrum disorder. This article provides a comprehensive review of the research and a case study of a 16-year-old male with autism who experienced a brief reactive psychosis.

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4. Cohen IL, Liu X, Hudson M, Gillis J, Cavalari RN, Romanczyk RG, Karmel BZ, Gardner JM. {{Using the PDD Behavior Inventory as a Level 2 Screener: A Classification and Regression Trees Analysis}}. {J Autism Dev Disord}. 2016.

In order to improve discrimination accuracy between Autism Spectrum Disorder (ASD) and similar neurodevelopmental disorders, a data mining procedure, Classification and Regression Trees (CART), was used on a large multi-site sample of PDD Behavior Inventory (PDDBI) forms on children with and without ASD. Discrimination accuracy exceeded 80 %, generalized to an independent validation set, and generalized across age groups and sites, and agreed well with ADOS classifications. Parent PDDBIs yielded better results than teacher PDDBIs but, when CART predictions agreed across informants, sensitivity increased. Results also revealed three subtypes of ASD: minimally verbal, verbal, and atypical; and two, relatively common subtypes of non-ASD children: social pragmatic problems and good social skills. These subgroups corresponded to differences in behavior profiles and associated bio-medical findings.

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5. Cribb SJ, Olaithe M, Di Lorenzo R, Dunlop PD, Maybery MT. {{Embedded Figures Test Performance in the Broader Autism Phenotype: A Meta-analysis}}. {J Autism Dev Disord}. 2016.

People with autism show superior performance to controls on the Embedded Figures Test (EFT). However, studies examining the relationship between autistic-like traits and EFT performance in neurotypical individuals have yielded inconsistent findings. To examine the inconsistency, a meta-analysis was conducted of studies that (a) compared high and low Autism-Spectrum Quotient (AQ) groups, and (b) treated AQ as a continuous variable. Outcomes are consistent with superior visual search forming part of the broader autism phenotype, but in existing literature, this is evident only when comparing extreme groups. Reanalysis of data from previous studies suggests findings are unlikely to be driven by a small number of high scorers. Monte Carlo simulations are used to illustrate the effect of methodological differences on results.

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6. Edmiston EK, Jones RM, Corbett BA. {{Physiological Response to Social Evaluative Threat in Adolescents with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2016.

The Trier Social Stress Test (TSST) was employed to study response to social evaluative threat in male adolescents with Autism Spectrum Disorder (ASD, n = 21) and typical development (n = 13). Participants wore a mobile electrocardiogram to collect heart rate data. There were significant group effects on respiratory sinus arrhythmia (RSA), a measure of parasympathetic nervous system function, with lower values in ASD (F = 4.97). Bivariate correlations also showed a significant relationship between parent reports of social problems and RSA response to the TSST (r = -0.586). These findings suggest that autonomic dysregulation may contribute to social deficits in adolescents with ASD.

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7. Eilam-Stock T, Wu T, Spagna A, Egan LJ, Fan J. {{Neuroanatomical Alterations in High-Functioning Adults with Autism Spectrum Disorder}}. {Front Neurosci}. 2016; 10: 237.

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental condition, affecting cognition and behavior throughout the life span. With recent advances in neuroimaging techniques and analytical approaches, a considerable effort has been directed toward identifying the neuroanatomical underpinnings of ASD. While gray-matter abnormalities have been found throughout cortical, subcortical, and cerebellar regions of affected individuals, there is currently little consistency across findings, partly due to small sample-sizes and great heterogeneity among participants in previous studies. Here, we report voxel-based morphometry of structural magnetic resonance images in a relatively large sample of high-functioning adults with ASD (n = 66) and matched typically-developing controls (n = 66) drawn from multiple studies. We found decreased gray-matter volume in posterior brain regions, including the posterior hippocampus and cuneus, as well as increased gray-matter volume in frontal brain regions, including the medial prefrontal cortex, superior and inferior frontal gyri, and middle temporal gyrus in individuals with ASD. We discuss our results in relation to findings obtained in previous studies, as well as their potential clinical implications.

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8. Gabis LV, Gruber N, Berkenstadt M, Shefer S, Attia OL, Mula D, Cohen Y, Elizur SE. {{Fragile X Premutation Carrier Epidemiology and Symptomatology in Israel-Results from a Tertiary Child Developmental Center}}. {Cerebellum}. 2016.

Fragile X syndrome (FXS) is the most prevalent known genetically inherited cause for autism and intellectual disability. Premutation state can cause several clinical disorders as well. We aimed to perform a nesting approach to acquire data with regard to first degree relatives of index fragile X cases at the largest child development center in Israel in order to map characteristics of Israeli FXS permutation women carriers. Seventy-nine women were referred due to a related fragile X syndrome patient, mainly an offspring or sibling. General information regarding demographics, ethnicity, and associated medical conditions were collected using interviews and structured questionnaires. Thirteen (17 %) of the women who were referred as « carrier » were proven to be actually full mutation. The mean years of education were 14 (+/-1.51, range 12-17). Twenty-one women (27 %) originated from Tunisia (mainly from the island of Djerba). Ten women (13 %) reported delivery of their affected offspring beyond 41 gestational weeks. Twenty-two percent of women with premutation reported symptoms consistent with learning difficulties, mainly dyscalculia, and 14 % reported ADHD symptoms. Awareness about clinical disorders of the carriers was existent only in 25 % of the patients. Increased awareness and knowledge dissemination concerning premutation symptomatology and associated medical conditions are warranted. We suggest a national registry to be installed in different countries in order to identify fragile X premutation carriers at increased risk for various medical complications.

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9. Keenan BM, Newman LK, Gray KM, Rinehart NJ. {{Parents of Children with ASD Experience More Psychological Distress, Parenting Stress, and Attachment-Related Anxiety}}. {J Autism Dev Disord}. 2016.

There has been limited study of the relationship between child attachment and caregiver wellbeing amongst children with autism spectrum disorder (ASD). This study examined self-reported child attachment quality alongside caregivers’ report of their own psychological distress, parenting stress and attachment style, amongst 24 children with high-functioning autism or Asperger’s disorder (ASD; aged 7-14 years) and 24 typically developing children (aged 7-12 years), and their primary caregiver. Children with ASD were no less secure, but their caregivers were more stressed and reported more attachment-related anxiety, compared to typically developing dyads. Child attachment security was related to caregiver psychological distress and attachment style, but only amongst typically developing children. Impacts of emotion processing impairments on caregiver-child relationships in ASD are discussed.

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10. Kim SH, Kim YS, Koh YJ, Lim EC, Kim SJ, Leventhal BL. {{Often Asked but Rarely Answered: Can Asians Meet DSM-5/ICD-10 Autism Spectrum Disorder Criteria?}}. {J Child Adolesc Psychopharmacol}. 2016.

OBJECTIVES: To evaluate whether Asian (Korean children) populations can be validly diagnosed with autism spectrum disorder (ASD) using Western-based diagnostic instruments and criteria based on Diagnostic and Statistical Manual on Mental Disorders, 5th edition (DSM-5; American Psychiatric Association 2013 ). METHODS: Participants included an epidemiologically ascertained 7-14-year-old (N = 292) South Korean cohort from a larger prevalence study (N = 55,266). Main outcomes were based on Western-based diagnostic methods for Korean children using gold standard instruments, Autism Diagnostic Interview-Revised, and Autism Diagnostic Observation Schedule. Factor analysis and ANOVAs were performed to examine factor structure of autism symptoms and identify phenotypic differences between Korean children with ASD and non-ASD diagnoses. RESULTS: Using Western-based diagnostic methods, Korean children with ASD were successfully identified with moderate-to-high diagnostic validity (sensitivities/specificities ranging 64%-93%), strong internal consistency, and convergent/concurrent validity. The patterns of autism phenotypes in a Korean population were similar to those observed in a Western population with two symptom domains (social communication and restricted and repetitive behavior factors). Statistically significant differences in the use of socially acceptable communicative behaviors (e.g., direct gaze, range of facial expressions) emerged between ASD versus non-ASD cases (mostly p < 0.001), ensuring that these can be a similarly valid part of the ASD phenotype in both Asian and Western populations. CONCLUSIONS: Despite myths, biases, and stereotypes about Asian social behavior, Asians (at least Korean children) typically use elements of reciprocal social interactions similar to those in the West. Therefore, standardized diagnostic methods widely used for ASD in Western culture can be validly used as part of the assessment process and research with Koreans and, possibly, other Asians. Lien vers le texte intégral (Open Access ou abonnement)

11. Krakowiak P, Walker CK, Tancredi D, Hertz-Picciotto I, Van de Water J. {{Autism-specific maternal anti-fetal brain autoantibodies are associated with metabolic conditions}}. {Autism Res}. 2016.

Approximately 23% of mothers of children with autism spectrum disorder (ASD) produce specific patterns of autoantibodies to fetal brain proteins that have been detected in only 1% of mothers of typically developing children. The biological mechanisms underlying the development of ASD-specific maternal autoantibodies are poorly understood. We sought to determine whether ASD-specific maternal autoantibodies identified postnatally were associated with metabolic conditions (MCs) during gestation. Participants were 227 mothers of 2-5 year old children with confirmed ASD, enrolled in CHARGE (Childhood Autism Risk from Genetics and the Environment) between January 2003 and April 2008, and from whom blood samples were collected and analyzed for anti-fetal brain autoantibodies (Ab+). MCs included diabetes, hypertensive disorders, and prepregnancy obesity or overweight, ascertained from medical records or structured telephone interviews. Log-linear regression models were performed to estimate prevalence ratios and 95% confidence intervals (CI) based on robust standard errors. Fifty-six (25%) mothers were Ab+. Ab+ prevalence was higher among mothers with diabetes, hypertensive disorders, or overweight compared to healthy mothers, but differences were not statistically significant. In a subset of 145 mothers whose children exhibited severe ASD (31 Ab+), those diagnosed with type 2 or gestational diabetes were 2.7-fold more likely to be Ab+ (95% CI 1.1, 6.6), controlling for delivery payer and smoking. Gestational diabetes specifically was associated with a 3.2-fold increased Ab+ prevalence (95% CI 1.2, 8.6). In this exploratory study, mothers whose children had severe ASD and who experienced diabetes were more likely to have anti-fetal brain autoantibodies 2-5 years later. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.

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12. Macizo P, Soriano MF, Paredes N. {{Phonological and Visuospatial Working Memory in Autism Spectrum Disorders}}. {J Autism Dev Disord}. 2016.

We evaluated phonological and visuospatial working memory (WM) in autism spectrum disorders. Autistic children and typically developing children were compared. We used WM tasks that measured phonological and visuospatial WM up to the capacity limit of each children. Overall measures of WM did not show differences between autistic children and control children. However, when the recall of children was examined in detail, autistic children showed reduced phonological WM compared with control children. Moreover, phonological and visuospatial WM did not increase with the age of autistic children while a development of phonological and visuospatial WM with age was found in control children. The pattern of results is discussed in terms of previous studies about WM and autism.

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13. Mouga S, Cafe C, Almeida J, Marques C, Duque F, Oliveira G. {{Intellectual Profiles in the Autism Spectrum and Other Neurodevelopmental Disorders}}. {J Autism Dev Disord}. 2016.

The influence of specific autism spectrum disorder (ASD) deficits in Intelligence Quotients (IQ), Indexes and subtests from the Wechsler Intelligence Scale for Children-III was investigated in 445 school-aged children: ASD (N = 224) and other neurodevelopmental disorders (N = 221), matched by Full-Scale IQ and chronological age. ASD have lower scores in the VIQ than PIQ. The core distinctive scores between groups are Processing Speed Index and « Comprehension » and « Coding » subtests with lower results in ASD. ASD group with normal/high IQ showed highest score on « Similarities » subtest whereas the lower IQ group performed better on « Object Assembly ». The results replicated our previous work on adaptive behaviour, showing that adaptive functioning is positively correlated with intellectual profile, especially with the Communication domain in ASD.

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14. Nguyen P, Seo JB, Ahn HM, Koh YH. {{Drosophila Torsin Protein Regulates Motor Control and Stress Sensitivity and Forms a Complex with Fragile-X Mental Retardation Protein}}. {Neural Plast}. 2016; 2016: 6762086.

We investigated unknown in vivo functions of Torsin by using Drosophila as a model. Downregulation of Drosophila Torsin (DTor) by DTor-specific inhibitory double-stranded RNA (RNAi) induced abnormal locomotor behavior and increased susceptibility to H2O2. In addition, altered expression of DTor significantly increased the numbers of synaptic boutons. One important biochemical consequence of DTor-RNAi expression in fly brains was upregulation of alcohol dehydrogenase (ADH). Altered expression of ADH has also been reported in Drosophila Fragile-X mental retardation protein (DFMRP) mutant flies. Interestingly, expression of DFMRP was altered in DTor mutant flies, and DTor and DFMRP were present in the same protein complexes. In addition, DTor and DFMRP immunoreactivities were partially colocalized in several cellular organelles in larval muscles. Furthermore, there were no significant differences between synaptic morphologies of dfmrp null mutants and dfmrp mutants expressing DTor-RNAi. Taken together, our evidences suggested that DTor and DFMRP might be present in the same signaling pathway regulating synaptic plasticity. In addition, we also found that human Torsin1A and human FMRP were present in the same protein complexes, suggesting that this phenomenon is evolutionarily conserved.

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15. Nicholas DB, Zwaigenbaum L, Muskat B, Craig WR, Newton AS, Kilmer C, Greenblatt A, Roberts W, Cohen-Silver J. {{Experiences of emergency department care from the perspective of families in which a child has autism spectrum disorder}}. {Soc Work Health Care}. 2016; 55(6): 409-26.

Care for children with autism spectrum disorder (ASD) in the emergency department (ED) is increasingly recognized as difficult. Communication, sensory and behavioral challenges in a high intensity environment pose risks for negative experiences and outcomes. Through semi-structured interviews, parents (n = 31) and their children (n = 4) with ASD shared their perspectives on ED care. Participants identified issues that negatively affected care experiences, including care processes, communication issues, insufficient staff knowledge about ASD, and inadequate partnership with parents. Elements contributing to an improved ED experience were also cited, including staff knowledge about ASD, child- and family-centered care, and clarity of communication. Findings inform an emerging model of ED care. Recommendations for capacity building and practice development are offered.

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16. Noroozi R, Taheri M, Movafagh A, Mirfakhraie R, Solgi G, Sayad A, Mazdeh M, Darvish H. {{Glutamate receptor, metabotropic 7 (GRM7) gene variations and susceptibility to autism: A case-control study}}. {Autism Res}. 2016.

Autism spectrum disorder (ASD) as a synaptopathy is revealed to be pertained to aberrant glutamatergic neurotransmission. Glutamate receptor, metabotropic 7 (GRM7), a receptor coding gene of this pathway, is a new candidate gene for autism. The aim of this study was to examine if there is a relationship between genetic variants rs779867 and rs6782011 of GRM7 with ASD. The present research was designed as a population-based, case-control study including 518 ASD patients versus 472 control individuals. The results showed that the frequency of rs779867 G/G genotype was significantly higher in ASD patients compared to healthy controls (P = 0.0001). Also, the G allele of this SNP was found to be significantly more frequent in the patients than control group (P = 0.0001). Haplotype analysis exhibited significant association of two estimated block of rs6782011/rs779867 in ASD patients versus control group. We found higher significant frequency of GT haplotype and lower frequencies of AT and AC haplotypes in the patients group compared to healthy controls (P = 0.001, P = 0.006, and P = 0.05, respectively). Our study indicated that the rs779867 polymorphism is associated with ASD; thus, results of this study provide supportive evidence of association of the GRM7 gene with ASD. Autism Res 2016. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.

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17. O’Handley RD, Dadakhodjaeva K, Radley KC, Dart EH. {{Promoting independent ambulation: A case study of an elementary school student with developmental disabilities}}. {Res Dev Disabil}. 2016; 56: 153-9.

The limited independent ambulation of individuals with developmental disabilities may be improved with the utilization of support walker devices. In the present study, a forward chaining procedure with an embedded changing criterion component was used to teach an elementary school student with multiple disabilities to acquire and maintain the skills needed to use his walker device successfully, and to increase his total distance walked while using his walker device. Results indicated that the student quickly acquired three of the four requisite steps necessary to use the walker device, but eventually acquired all four steps after procedural modifications. After mastering the four steps, the student gradually increased his total distance walked. Results were maintained when assessed two months post-intervention. Limitations and directions for future research are discussed.

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18. Okuno H, Yamamoto T, Tatsumi A, Mohri I, Taniike M. {{Simultaneous Training for Children with Autism Spectrum Disorder and Their Parents with a Focus on Social Skills Enhancement}}. {Int J Environ Res Public Health}. 2016; 13(6).

The objective of this study was to evaluate the effectiveness of simultaneous training for children with autism spectrum disorder (ASD) and their parents, with a focus on social skills enhancement (STSSE) by evaluating behavioral changes in children with ASD and changes in family functioning. STSSE was conducted on 17 children of elementary school age with ASD and their parents. Changes in scores on the social skills scale for education (SS-scale), the child behavior checklist, the Feetham Family Functioning Survey (FFFS), and the confidence degree questionnaire for families (CDQ) were used to assess the effectiveness of STSSE. Improvements were seen for « Communication Skills » on the children’s SS-scale (p = 0.029). Significant improvements were seen in the mothers’ FFFS scores for « The 4th factor: illness and worries » (p = 0.016) and in the median CDQ scores for one of 18 items after STSSE (p = 0.01). Although additional studies with larger sample sizes will be necessary before these findings are generalizable, the positive changes seen in both parents and children as a result of STSSE are promising.

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19. Self TL, Parham DF. {{Students’ self-perceptions of interprofessional education following participation on a diagnostic team for autism spectrum disorder}}. {J Interprof Care}. 2016: 1-3.

Interprofessional education is essential for producing future allied-health and education professionals. Unfortunately, opportunities for students to get authentic interprofessional field-based experiences are lacking. This pilot study explored students’ self-perceptions towards interprofessional education (IPE) following participation on an interprofessional diagnostic team designed to rule in or out the diagnosis of autism spectrum disorder (ASD). Thirty-nine students from seven professions responded to a survey before and after completing this interprofessional education experience. The results indicated that the students’ self-perceptions remained consistent during the experience. They reflected positive self-perceptions in the areas of collaboration, professional identity, and the desire to work with others, all in the context of an ASD-focused team. The findings suggest that students entering the IPE experience with positive expectations remained positive during the experience. This pilot study provides support for the benefits of providing students with the opportunity to engage in authentic collaborative practice when working with children with ASD.

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20. Wong CM, Koh HC. {{Brief Report: Investigating the Implications of Applying the New DSM-5 Criteria for Diagnosing Autism Spectrum Disorder in a Preschool Population in Singapore}}. {J Autism Dev Disord}. 2016.

Diagnostic reports for 206 children who underwent an assessment for autism spectrum disorder (ASD) using the DSM-IV-TR criteria, were re-evaluated using the DSM-5 criteria. Mean age of the children at time of diagnosis was 3 years 10 months. Of the 202 children diagnosed with ASD on the DSM-IV-TR, 184 (91.1 %) also met the DSM-5 criteria for ASD. The overall concordance rate of ASD diagnosis on the DSM-IV-TR and DSM-5 was higher than that reported in other studies. Of the 18 children who did not meet DSM-5 criteria for ASD, 16 children met all social communication criteria but did not fulfil at least two restricted and repetitive behaviour (RRB) criteria. Six of those children had further RRBs emerging later on follow-up.

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21. Wu Y, Zhong W, Cui N, Johnson CM, Xing H, Zhang S, Jiang C. {{Characterization of Rett Syndrome-like phenotypes in Mecp2-knockout rats}}. {J Neurodev Disord}. 2016; 8: 23.

BACKGROUND: Rett Syndrome (RTT) is a neurodevelopmental disease caused by the disruption of the MECP2 gene. Several mouse models of RTT have been developed with Mecp2 disruptions. Although the mouse models are widely used in RTT research, results obtained need to be validated in other species. Therefore, we performed these studies to characterize phenotypes of a novel Mecp2 (-/Y) rat model and compared them with the Mecp2 (tm1.1Bird) mouse model of RTT. METHODS: RTT-like phenotypes were systematically studied and compared between Mecp2 (-/Y) rats and Mecp2 (-/Y) mice. In-cage conditions of the rats were monitored. Grip strength and spontaneous locomotion were used to evaluate the motor function. Three-chamber test was performed to show autism-type behaviors. Breathing activity was recorded with the plethysmograph. Individual neurons in the locus coeruleus (LC) were studied in the whole-cell current clamp. The lifespan of the rats was determined with their survival time. RESULTS: Mecp2 (-/Y) rats displayed growth retardation, malocclusion, and lack of movements, while hindlimb clasping was not seen. They had weaker forelimb grip strength and a lower rate of locomotion than the WT littermates. Defects in social interaction with other rats were obvious. Breathing frequency variation and apnea in the null rats were significantly higher than in the WT. LC neurons in the null rats showed excessive firing activity. A half of the null rats died in 2 months. Most of the RTT-like symptoms were comparable to those seen in Mecp2 (-/Y) mice, while some appeared more or less severe. The findings that most RTT-like symptoms exist in the rat model with moderate variations and differences from the mouse models support the usefulness of both Mecp2 (-/Y) rodent models. CONCLUSIONS: The novel Mecp2 (-/Y) rat model recapitulated numerous RTT-like symptoms as Mecp2 (-/Y) mouse models did, which makes it a valuable alternative model in the RTT studies when the body size matters.

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22. Zhang S, Johnson CM, Cui N, Xing H, Zhong W, Wu Y, Jiang C. {{An optogenetic mouse model of rett syndrome targeting on catecholaminergic neurons}}. {J Neurosci Res}. 2016.

Rett syndrome (RTT) is a neurodevelopmental disorder affecting multiple functions, including the norepinephrine (NE) system. In the CNS, NE is produced mostly by neurons in the locus coeruleus (LC), where defects in intrinsic neuronal properties, NE biosynthetic enzymes, neuronal CO2 sensitivity, and synaptic currents have been reported in mouse models of RTT. LC neurons in methyl-CpG-binding protein 2 gene (Mecp2) null mice show a high rate of spontaneous firing, although whether such hyperexcitability might increase or decrease the NE release from synapses is unknown. To activate the NEergic axonal terminals selectively, we generated an optogenetic mouse model of RTT in which NEergic neuronal excitability can be manipulated with light. Using commercially available mouse breeders, we produced a new strain of double-transgenic mice with Mecp2 knockout and channelrhodopsin (ChR) knockin in catecholaminergic neurons. Several RTT-like phenotypes were found in the tyrosine hydroxylase (TH)-ChR-Mecp2-/Y mice, including hypoactivity, low body weight, hindlimb clasping, and breathing disorders. In brain slices, optostimulation produced depolarization and an increase in the firing rate of LC neurons from TH-ChR control mice. In TH-ChR control mice, optostimulation of presynaptic NEergic neurons augmented the firing rate of hypoglossal neurons (HNs), which was blocked by the alpha-adrenoceptor antagonist phentolamine. Such optostimulation of NEergic terminals had almost no effect on HNs from two or three TH-ChR-Mecp2-/Y mice, indicating that excessive excitation of presynaptic neurons does not benefit NEergic modulation in mice with Mecp2 disruption. These results also demonstrate the feasibility of generating double-transgenic mice for studies of RTT with commercially available mice, which are inexpensive, labor/time efficient, and promising for cell-specific stimulation. (c) 2016 Wiley Periodicals, Inc.

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