1. Becker MM, Riesgo RS, Roesler R, Bosa C, Ohlweiler L, Backes B, Endres RG, Zanon RB, Marchezan J, Schwartsmann G. {{Improvement in Symptoms of Autism Spectrum Disorder in Children With the Use of Gastrin-Releasing Peptide: An Open Trial}}. {Clin Neuropharmacol}. 2016.
OBJECTIVES: The aim of this study was to determine the efficacy and tolerability of gastrin-releasing peptide (GRP) for core symptoms of autism spectrum disorder. METHODS: This is a prospective, open-label study with 160 pmol/kg of GRP tested in 10 children with autism. Outcome measures used were the Clinical Global Impressions-Improvement Scale, Aberrant Behavior Checklist (ABC), Childhood Autism Rating Scale, and Autism Diagnostic Interview-Revised. Positive response was defined as a score of 1 (very much improved) or 2 (much improved) on the Clinical Global Impressions-Improvement Scale and an improvement of 25% or greater on at least 1 subscale of ABC. RESULTS: Six (60%) of the 10 subjects responded to GRP. Improvements were observed on the ABC irritability and hyperactivity subscales in 80% of patients, and 70% exhibited improvement on the social withdrawal subscale. On the Childhood Autism Rating Scale, there was a mean reduction of 4 points (4.3 +/- 2.9). Analysis of the Autism Diagnostic Interview-Revised results detected significant improvements in the domain that assesses social interaction, with a mean reduction of 2.4 points (2.4 +/- 2.83). Adverse effects occurred in 3 patients. CONCLUSIONS: Gastrin-releasing peptide was safe and well tolerated by most subjects and may be effective for core symptoms of autism.
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2. Diebo BG, Gammal I, Ha Y, Yoon SH, Chang JW, Kim B, Matsumoto M, Yamato Y, Takeuchi D, Hosogane N, Yagi M, Taneichi H, Schwab F, Lafage V, Ames C. {{Role of Ethnicity in Alignment Compensation: Propensity Matched Analysis of Differential Compensatory Mechanism Recruitment Patterns for Sagittal Malalignment in 288 ASD Patients from Japan, Korea and United States}}. {Spine (Phila Pa 1976)}. 2016.
STUDY DESIGN: Retrospective review of ASD patients in a multi-ethnic database OBJECTIVE.: To investigate the role of ethnicity on recruitment of compensatory mechanisms for sagittal spinal deformity. SUMMARY OF BACKGROUND DATA: While the impacts of age, gender and pelvic morphology on the ability to compensate for sagittal malalignment have been investigated, the role of ethnicity in compensatory mechanism recruitment is poorly understood. METHODS: Patients from USA (85% Caucasian) > 25 y/o were propensity matched by age, gender, and pelvic incidence with patients from Korea and Japan. Only primary patients or those with existing fusion below T12 were retained for analysis. Groups were sub-classified by deformity severity (aligned: sagittal vertical axis (SVA) < 50 mm; moderate malalignment: SVA 50-100 mm; severe malalignment: SVA >100 mm). Radiographic measurements including pelvic retroversion, thoracic kyphosis, loss of lumbar lordosis (PI minus LL), cervical lordosis and cervical SVA were compared between the groups. RESULTS: There were 288 patients (96 each in USA, KOR, JPN), with similar age (64-67yrs) and PI (49-53 degrees ). USA had smaller PI-LL in every alignment group (p < 0.05). In moderate malalignment, JPN had more pelvic retroversion than USA (30 degrees vs. 20 degrees ), and KOR had more thoracic hypokyphosis than USA (15 vs. 31 degrees ). In severe malalignment, JPN had more pelvic retroversion than USA (39 degrees vs. 27 degrees ), and KOR had more thoracic hypokyphosis than USA (15 degrees vs. 31 degrees ). KOR had smaller cSVA than USA in both aligned (11 vs. 27 mm) and moderate (19 vs. 31 mm) malalignment. In severe malalignment, KOR had less cervical lordosis (13 degrees KOR vs. 15 degrees USA vs. 27 degrees JPN). All differences with P < 0.05. CONCLUSIONS: Compensation for sagittal is ethnicity dependent. Korean patients favor thoracic compensation via hypokyphosis, and Japanese patients favor pelvic compensation via retroversion. Patient ethnicity should be considered when evaluating the sagittal plane and surgical correction strategies. LEVEL OF EVIDENCE: 3. Lien vers le texte intégral (Open Access ou abonnement)
3. Ferguson BJ, Marler S, Altstein LL, Lee EB, Akers J, Sohl K, McLaughlin A, Hartnett K, Kille B, Mazurek M, Macklin EA, McDonnell E, Barstow M, Bauman ML, Margolis KG, Veenstra-VanderWeele J, Beversdorf DQ. {{Psychophysiological Associations with Gastrointestinal Symptomatology in Autism Spectrum Disorder}}. {Autism Res}. 2016.
Autism spectrum disorder (ASD) is often accompanied by gastrointestinal disturbances, which also may impact behavior. Alterations in autonomic nervous system functioning are also frequently observed in ASD. The relationship between these findings in ASD is not known. We examined the relationship between gastrointestinal symptomatology, examining upper and lower gastrointestinal tract symptomatology separately, and autonomic nervous system functioning, as assessed by heart rate variability and skin conductance level, in a sample of 120 individuals with ASD. Relationships with co-occurring medical and psychiatric symptoms were also examined. While the number of participants with significant upper gastrointestinal tract problems was small in this sample, 42.5% of participants met criteria for functional constipation, a disorder of the lower gastrointestinal tract. Heart rate variability, a measure of parasympathetic modulation of cardiac activity, was found to be positively associated with lower gastrointestinal tract symptomatology at baseline. This relationship was particularly strong for participants with co-occurring diagnoses of anxiety disorder and for those with a history of regressive ASD or loss of previously acquired skills. These findings suggest that autonomic function and gastrointestinal problems are intertwined in children with ASD; although it is not possible to assess causality in this data set. Future work should examine the impact of treatment of gastrointestinal problems on autonomic function and anxiety, as well as the impact of anxiety treatment on gastrointestinal problems. Clinicians should be aware that gastrointestinal problems, anxiety, and autonomic dysfunction may cluster in children with ASD and should be addressed in a multidisciplinary treatment plan. Autism Res 2016. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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4. Folmsbee SS, Wilcox DR, Tyberghein K, De Bleser P, Tourtellotte WG, van Hengel J, van Roy F, Gottardi CJ. {{alphaT-catenin in restricted brain cell types and its potential connection to autism}}. {J Mol Psychiatry}. 2016; 4: 2.
BACKGROUND: Recent genetic association studies have linked the cadherin-based adherens junction protein alpha-T-catenin (alphaT-cat, CTNNA3) with the development of autism. Where alphaT-cat is expressed in the brain, and how its loss could contribute to this disorder, are entirely unknown. METHODS: We used the alphaT-cat knockout mouse to examine the localization of alphaT-cat in the brain, and we used histology and immunofluorescence analysis to examine the neurobiological consequences of its loss. RESULTS: We found that alphaT-cat comprises the ependymal cell junctions of the ventricles of the brain, and its loss led to compensatory upregulation of alphaE-cat expression. Notably, alphaT-cat was not detected within the choroid plexus, which relies on cell junction components common to typical epithelial cells. While alphaT-cat was not detected in neurons of the cerebral cortex, it was abundantly detected within neuronal structures of the molecular layer of the cerebellum. Although alphaT-cat loss led to no overt differences in cerebral or cerebellar structure, RNA-sequencing analysis from wild type versus knockout cerebella identified a number of disease-relevant signaling pathways associated with alphaT-cat loss, such as GABA-A receptor activation. CONCLUSIONS: These findings raise the possibility that the genetic associations between alphaT-cat and autism may be due to ependymal and cerebellar defects, and highlight the potential importance of a seemingly redundant adherens junction component to a neurological disorder.
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5. Heyde E, Dhar M, Hellemans H, Schoentjes E, Van West D. {{[Prevalence of the use of psychoactive medication to treat young persons with autism spectrum disorder in the province of Antwerp, Belgium]}}. {Tijdschr Psychiatr}. 2016; 58(6): 446-54.
BACKGROUND: Very little information is available concerning the prevalence of the use of medication for treatment of individuals with autism spectrum disorder (ASD), particularly in European countries. Earlier studies have shown that a large number of patients with ASD use at least one psychoactive drug and that the numbers are increasing. Even in the nineties, studies suggested that the frequent use of psychoactive medication was widespread, although at the time there were only limited grounds for this assumption.
AIM: To assess the prevalence with which psychoactive medication and complementary and alternative medicine (CAM) are being used for treating young people with ASD, and also to investigate relations between medication use and a number of individual characteristics that are included in the Behavioral Model of Health Service Use.
METHOD: The study sample (0-17 years) in the province of Antwerp, Belgium, was recruited by various means. We used a questionnaire that had been previously used in North American studies and that had to be completed by the parents of the young persons involved in the study.
RESULTS: We included data from 263 questionnaires. In our sample 42.6% of the young persons used one or more one psychoactive drug. More than 12.2% used more than one drug. The most frequently used psychoactive drugs were ADHD-medication (31.6%) and antipsychotics (16.7%). About 14% used at least one CAM. We found a positive relationship between the use of medication and psychiatric comorbidity and/or epilepsy, the severity of autism and the parents’ living conditions.
CONCLUSION: We found a relatively low use of antipsychotics, antidepressants, mood stabilisers and sedatives, the prevalence being lower that that reported in North American studies. Our findings appear to be in accordance with current clinical guidelines.
6. Honda H, Saito E. {{Factors related to care burden among parents of adults with developmental disabilities}}. {Nihon Koshu Eisei Zasshi}. 2016; 63(5): 252-9.
Purpose To clarify the care burden and associated factors among parents of adults with developmental disabilities in order to obtain suggestions for the family supports.Methods Subjects included 125 parents of adults (aged 18 or older) with developmental disabilities. All parents belonged to and/or contacted parents’ associations, mental health welfare centers, and support centers for persons with developmental disabilities in the Tokyo metropolitan area. Participants completed self-report questionnaire surveys from October to November 2011. Questionnaire items included parent and adult demographic factors, parent care burden, disability state, and support available from family and others. The level of care burden was measured using the short Japanese version of the Zarit Burden Interview (J-ZBI_8).Results A total of 64 responses were analyzed. The mean J-ZBI_8 score was 12.8 (SD=7.2). Adults’ most common diagnoses were autism (50%), Asperger’s syndrome (25%), and pervasive developmental disorder (20%). state of daily life (P=0.041) and presence of secondary disability (P=0.001) were associated with parents’ care burden in age-adjusted multiple linear regression analysis.Discussion Overall, the results suggest that it is important to assess developmental disability status and family support when developing programs to reduce parental care burden.
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7. Huang JY, Tian Y, Wang HJ, Shen H, Wang H, Long S, Liao MH, Liu ZR, Wang ZM, Li D, Tao RR, Cui TT, Moriguchi S, Fukunaga K, Han F, Lu YM. {{Functional Genomic Analyses Identify Pathways Dysregulated in Animal Model of Autism}}. {CNS Neurosci Ther}. 2016.
BACKGROUND: Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders that display complicated behavioral symptoms. METHODS: Using gene expressing profiling and the weighted gene co-expression network analysis (WGCNA), we studied genes coregulated by similar factors such as genetic variants or environmental effects in the hippocampus in an animal model of autism. RESULTS: From microarray data, we identified 21,388 robustly expressed genes of which 721 genes were found to be differently expressed in the valproic acid-treated group compared to the control group. WGCNA identified multiple co-expression modules known to associate with cognitive function, inflammation, synaptic, and positive regulation of protein kinase activating. Many of these modules, however, have not been previously linked to autism spectrum disorders which included G-protein signaling, immunity, and neuroactive ligand-receptor interaction pathway. The downregulation of the highly connected (hub) genes Taar7h and Taar7b in neuroactive ligand-receptor interaction pathway was validated by qRT-PCR. Immunoblotting and immunohistochemistry further showed that TAAR7 expression was downregulated not only in valproic acid-treated animals, but also BTBR T+tf/J mice. CONCLUSIONS: This study highlights the advantages of gene microarrays to uncover co-expression modules associated with autism and suggests that Taars and related gene regulation networks may play a significant role in autism.
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8. Li Q, Chen CF, Wang DY, Lu YT, Huan Y, Fang SX, Han Y, Ge RC, Chen XW. {{Changes in growth factor levels in the cerebrospinal fluid of autism patients after transplantation of human umbilical cord blood mononuclear cells and umbilical cord-derived mesenchymal stem cells}}. {Genet Mol Res}. 2016; 15(2).
The aim of the current study was to evaluate the levels of growth factors in the cerebrospinal fluid (CSF) of patients with autism, after transplantation of human umbilical cord blood mononuclear cells (CBMNCs) and umbilical cord-derived mesenchymal stem cells (UCMSCs). Twenty patients received two CBMNC intravenous and intrathecal infusions, each followed by two UCMSC intrathecal injections. A 2-mL sample of CSF was taken before each intrathecal injection. CSF levels of hepatocyte growth factor (HGF), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) were determined by an enzyme-linked immunosorbent assay (ELISA). All data are reported as means +/- SD and were analyzed using the SPSS 10.0 software. One-way analysis of variance with post-hoc F- and Q-tests was performed for comparison. HGF, BDNF and NGF levels in the CSF were significantly increased after transplantation (P < 0.05), while bFGF levels did not change significantly. Therefore, transplantation of CBMNCs and UCMSCs could increase HGF, BDNF and NGF levels in the CSF of patients with autism. Lien vers le texte intégral (Open Access ou abonnement)
9. Low Kapalu CM, Gartstein MA. {{Boys with fragile X syndrome: investigating temperament in early childhood}}. {J Intellect Disabil Res}. 2016.
BACKGROUND: Fragile X syndrome (FXS) is an x-linked genetic disorder that represents the most common hereditary cause of Intellectual Disability (ID). Very specific behavioural features (e.g. attention deficit hyperactivity disorder and stereotyped behaviour) are associated with FXS in adolescents and adults, yet research on temperament and behavioural characteristics in young children with FXS has been more limited and less conclusive. METHOD: This study investigated temperament differences in young boys (3-7 years old) with FXS (N = 26) recruited from a national FXS centre and controls (N = 26) matched on age, gender and race. RESULTS: Compared with controls, boys with FXS exhibited less overall surgency/extraversion and effortful control. Boys with FXS also displayed significantly greater activity and shyness and less attentional focusing, inhibitory control, soothability and high intensity pleasure (tendency to enjoy intense/complex activities), relative to comparison children. A significant interaction between age and diagnosis (FXS or control) was observed for negative affectivity only. CONCLUSIONS: Attention difficulties commonly found in adolescents and adults with FXS appear to also be characteristic of young boys with FXS, as reflected by lower effortful control. Age-related findings concerning negative affectivity may be particularly significant, leading to improved intervention/preventative efforts.
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10. Matson JL, Cervantes PE, Peters WJ. {{Autism spectrum disorders: management over the lifespan}}. {Expert Rev Neurother}. 2016.
INTRODUCTION: For the majority of the autism spectrum disorder (ASD) population, symptoms begin within the first years of life and associated difficulties continue throughout the lifespan. Currently, the research literature focuses more heavily on problems in childhood. However, given that adulthood accounts for the majority of life, more focus should be placed on evidence-based, lifelong treatment and management strategies for ASD. AREAS COVERED: This paper reviews the topic of lifelong ASD management, primarily emphasizing issues in adolescence and adulthood. Among the topics discussed are timing and methods of treatment across the lifespan, and specific intervention targets that emerge or are more relevant to this older cohort. Expert Review: Several advances have been made in the treatment of adolescent and adult specific issues. However, research should continue to focus on these areas. Greater focus on coordination of care across disciplines and policy regarding ASD management over the lifespan is also required.
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11. Meng X, Wang W, Lu H, He LJ, Chen W, Chao E, Fiorotto ML, Tang B, Herrera JA, Seymour ML, Neul JL, Pereira FA, Tang J, Xue M, Zoghbi HY. {{Manipulations of MeCP2 in glutamatergic neurons highlight their contributions to Rett and other neurological disorders}}. {Elife}. 2016; 5.
Many postnatal onset neurological disorders such as autism spectrum disorders (ASDs) and intellectual disability are thought to arise largely from disruption of excitatory/inhibitory homeostasis. Although mouse models of Rett syndrome (RTT), a postnatal neurological disorder caused by loss-of-function mutations in MECP2, display impaired excitatory neurotransmission, the RTT phenotype can be largely reproduced in mice simply by removing MeCP2 from inhibitory GABAergic neurons. To determine what role excitatory signaling impairment might play in RTT pathogenesis, we generated conditional mouse models with Mecp2 either removed from or expressed solely in glutamatergic neurons. MeCP2 deficiency in glutamatergic neurons leads to early lethality, obesity, tremor, altered anxiety-like behaviors, and impaired acoustic startle response, which is distinct from the phenotype of mice lacking MeCP2 only in inhibitory neurons. These findings reveal a role for excitatory signaling impairment in specific neurobehavioral abnormalities shared by RTT and other postnatal neurological disorders.
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12. Ozsivadjian A, Hollocks MJ, Southcott J, Absoud M, Holmes E. {{Anxious Imagery in Children With and Without Autism Spectrum Disorder: An Investigation into Occurrence, Content, Features and Implications for Therapy}}. {J Autism Dev Disord}. 2016.
Mental imagery has been implicated in anxiety disorders in adults, but has not been investigated in child and adolescent populations. Anxiety is highly prevalent in autism spectrum disorder (ASD), and as people with ASD are often thought of as ‘visual thinkers’, the potential role of distressing imagery in children with ASD merits exploration. Participants aged 8-16 years were grouped as follows: ASD/high anxiety, ASD/low anxiety, non-ASD/high anxiety and non-ASD/low anxiety. Imagery and associated features were assessed using an interview. Group differences were found in number and frequency of images experienced. There were few differences between the groups in the characteristics of the spontaneous images, which included emotional valence, vividness, controllability and realism. Implications for treatment are discussed.
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13. Patterson KC, Hawkins VE, Arps KM, Mulkey DK, Olsen ML. {{MeCP2 Deficiency Results in Robust Rett-like Behavioral and Motor Deficits in Male and Female Rats}}. {Hum Mol Genet}. 2016.
Since the identification of MECP2 as the causative gene in the majority of Rett Syndrome (RTT) cases, transgenic mouse models have played a critical role in our understanding of this disease. The use of additional mammalian RTT models offers the promise of further elucidating critical early mechanisms of disease as well as providing new avenues for translational studies. We have identified significant abnormalities in growth as well as motor and behavioral function in a novel zinc-finger nuclease model of RTT utilizing both male and female rats throughout development. Male rats lacking MeCP2 (Mecp2 ZFN/y) were noticeably symptomatic as early as postnatal day 21, with most dying by postnatal day 55, while females lacking one copy of Mecp2 (Mecp2 ZFN/+) displayed a more protracted disease course. Brain weights of Mecp2 ZFN/y and Mecp2 ZFN/+ rats were significantly reduced by postnatal day 14 and 21, respectively. Early motor and breathing abnormalities were apparent in Mecp2 ZFN/y rats, whereas Mecp2 ZFN/+ rats displayed functional irregularities later in development. The large size of this species will provide profound advantages in the identification of early disease mechanisms and the development of appropriately timed therapeutics. The current study establishes a foundational basis for the continued utilization of this rat model in future RTT research.
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14. Ure K, Lu H, Wang W, Ito-Ishida A, Wu Z, He LJ, Sztainberg Y, Chen W, Tang J, Zoghbi HY. {{Restoration of Mecp2 expression in GABAergic neurons is sufficient to rescue multiple disease features in a mouse model of Rett Syndrome}}. {Elife}. 2016; 5.
The postnatal neurodevelopmental disorder Rett syndrome, caused by mutations in MECP2, produces a diverse array of symptoms, including loss of language, motor, and social skills and the development of hand stereotypies, anxiety, tremor, ataxia, respiratory dysrhythmias, and seizures. Surprisingly, despite the diversity of these features, we have found that deleting Mecp2 only from GABAergic inhibitory neurons in mice replicates most of this phenotype. Here we show that genetically restoring Mecp2 expression only in GABAergic neurons of male Mecp2 null mice enhanced inhibitory signaling, extended lifespan, and rescued ataxia, apraxia, and social abnormalities but did not rescue tremor or anxiety. Female Mecp2+/- mice showed a less dramatic but still substantial rescue. These findings highlight the critical regulatory role of GABAergic neurons in certain behaviors and suggest that modulating the excitatory/inhibitory balance through GABAergic neurons could prove a viable therapeutic option in Rett syndrome.
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15. Whyte H, Pecchioli Y, Oyewumi L, Kives S, Allen LM, Kirkham YA. {{Uterine length in adolescents with developmental disability: are ultrasounds necessary prior to insertion of the levonorgestrel intrauterine system?}}. {J Pediatr Adolesc Gynecol}. 2016.
STUDY OBJECTIVES: 1) to determine if there are any differences in uterine length between adolescents with developmental disability (DD) compared to their normally developing (ND) peers that may necessitate ultrasonography prior to insertion of levonorgestrel intrauterine system (LNG-IUS) in patients with DD and 2) to characterize LNG-IUS insertion procedure in adolescents with disabilities. DESIGN, SETTING, PARTICIPANTS: Retrospective cohort study of 223 adolescent females with or without developmental disabilities. 75 adolescents had DD; 33 underwent intrauterine system insertion in the operating room and 42 did not. Comparative cohort of 148 ND adolescents who had pelvic ultrasounds for abnormal uterine bleeding. The study period was between January 2006 and July 2013 at the Hospital for Sick Children, Toronto, Canada. Cases were identified from surgical databases and medical records. MAIN OUTCOME MEASURES: mean uterine length on pelvic ultrasound, demographics (age, age at menarche, time from menarche to ultrasound, weight), and descriptive statistics on intrauterine system insertion. RESULTS: There is a statistically significant difference (p=0.03) in uterine length between adolescents with and without developmental disability (6.7 vs 7.1 cm). However, this is not a clinically significant difference as insertion of LNG-IUS in patients with DD is successful in patients with uteri over 5cm long. There is no difference (p=0.97) in uterine length of adolescents with DD whether they had LNG-IUS insertion or not (6.7cm). Adolescents with DD were younger than adolescents without DD at time of ultrasound (p=0.01). However, among patients with DD, those who underwent IUS insertion were older (p= 0.001). Incidence of uterine anomaly in patients with DD is low (2.7%) and was the same as in ND adolescents. Rates of complications and expulsions were low and there were no failures of LNG-IUS insertion in adolescents with DD. CONCLUSIONS: Routine pelvic ultrasounds are not necessary prior to insertion of LNG-IUS for menstrual suppression in adolescents with developmental disability. Renal abnormalities, obstructive symptoms, and very small stature may necessitate imaging. Insertion under anaesthesia is often straightforward and successful with minimal complications.
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16. Zhang J, Zhang JX, Zhang QL. {{PI3K/AKT/mTOR-mediated autophagy in the development of autism spectrum disorder}}. {Brain Res Bull}. 2016.
AIM: To investigate the association between PI3K/AKT/mTOR-mediated autophagy and the pathogenesis of autism spectrum disorder (ASD). METHODS: A sodium valproate (VPA)-induced baby rat model of ASD was built. Nine pregnant rats were randomly assigned into three groups, with three rats for each group: healthy control group, VPA group and mTOR inhibition group, receiving different drug administrations. Baby rats were grouped according to the maternal rats. Social interaction of baby rats (35days after birth) was observed and their bilateral hippocampes were sliced. We used electron microscope analysis for observation of autophagosome formation, double immunofluorescence staining for location of LC3 II, TUNEL assay for observation of cell apoptosis, Western Blot assay was used for measurement of LC3 II, P62, p53, Bcl-2, PI3K/AKT/mTOR-related proteins and p-S6. RESULTS: VPA group had significantly lowered ability of social interaction than the control group and mTOR inhibition group (both P<0.05). The control group and the mTOTR inhibition group presented the visual of autophagosomes, while VPA group seldom had autophagosomes. By comparison with VPA group, mTOR group had a remarkable green fluorescence in the hippocampal CA1 (P<0.05). Western Blot assay revealved that mTOR inhibition group had a significantly higher LC3 II expression, higher LC3 II/LC3 I ratio, higher Bcl-2 expression and lower p53 than VPA group (all P<0.05). TUNEL assay showed that mTOR inhibition group had a significant smaller number of apoptotic cells in the hippocampal CA1. Besides, lowered expressions of p-PI3K, p-AKT and p-S6 were identified in the baby rats in mTOR inhibition group compared with VPA group (all P<0.05). CONCLUSION: mTOR inhibition can increase PI3K/AKT/mTOR-mediated autophagic activity and improve social interaction in VPA-induced ASD, providing a novel target and direction for the treatment of ASD. Lien vers le texte intégral (Open Access ou abonnement)
