RESUMO
CalDAG-GEFI (CDGI) is a protein highly enriched in the striatum, particularly in the principal spiny projection neurons (SPNs). CDGI is strongly down-regulated in two hyperkinetic conditions related to striatal dysfunction: Huntington's disease and levodopa-induced dyskinesia in Parkinson's disease. We demonstrate that genetic deletion of CDGI in mice disrupts dendritic, but not somatic, M1 muscarinic receptors (M1Rs) signaling in indirect pathway SPNs. Loss of CDGI reduced temporal integration of excitatory postsynaptic potentials at dendritic glutamatergic synapses and impaired the induction of activity-dependent long-term potentiation. CDGI deletion selectively increased psychostimulant-induced repetitive behaviors, disrupted sequence learning, and eliminated M1R blockade of cocaine self-administration. These findings place CDGI as a major, but previously unrecognized, mediator of cholinergic signaling in the striatum. The effects of CDGI deletion on the self-administration of drugs of abuse and its marked alterations in hyperkinetic extrapyramidal disorders highlight CDGI's therapeutic potential.
Assuntos
Dendritos , Fatores de Troca do Nucleotídeo Guanina/genética , Neostriado/fisiopatologia , Plasticidade Neuronal , Sistema Nervoso Parassimpático/fisiopatologia , Sinapses , Animais , Doenças dos Gânglios da Base/genética , Doenças dos Gânglios da Base/fisiopatologia , Doenças dos Gânglios da Base/psicologia , Estimulantes do Sistema Nervoso Central/farmacologia , Potenciais Pós-Sinápticos Excitadores/genética , Hipercinese/genética , Hipercinese/psicologia , Potenciação de Longa Duração , Masculino , Camundongos , Camundongos Knockout , Atividade Motora , Polimorfismo de Nucleotídeo Único , Receptor Muscarínico M1/genética , Receptor Muscarínico M1/fisiologia , Transtornos Relacionados ao Uso de Substâncias/genética , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/psicologiaRESUMO
Bisphenol S (BPS), an analogue of the controversial bisphenol A (BPA) that is found in epoxy resins and plastics, is a potential endocrine-disrupting chemical that can mimic endogenous hormone signaling. However, little is known about the behavioral or immunologic effects of BPS. The purpose of this study was to examine the impact of diets in BPS-treated mice in relation to hyperglycemia, development of type 1 diabetes, immunomodulation, and behavioral changes. Adult male and female nonobese diabetic excluded flora (NODEF) mice were exposed to environmentally relevant doses of BPS (VH, 30, or 300 µg/kg BW) and fed either a soy-based diet, a phytoestrogen-free diet, or a Western diet. NODEF male mice fed a soy-based diet exhibited a decreased curiosity/desire to explore, and possibly increased anxiety-like behavior and decreased short-term memory when exposed to BPS (300 µg/kg BW). In addition, these mice had significant increases in non-fasting blood glucose levels along with increased insulin sensitivity, impaired glucose tolerance, resistance to fasting and proinflammation. Although BPS had little effect on the glucose parameters in NODEF male mice fed a Western diet, there were decreases in %CD24+CD5+ and %B220+CD40L-cell populations and increases in distance traveled during the novel object test, suggesting hyperactivity. NODEF females fed a phytoestrogen-free diet exhibited slight decreases in time spent immobile during the tail suspension test in both the 30 and 300 µg/kg BW dose groups along with increases in %CD4+CD8+ and %Mac3+CD45R+ cell populations, signifying increased hyperactivity and anxiety-like behavior. In conclusion, BPS-exposed NODEF mice exhibited sex and diet-related changes in hyperglycemia, behaviors and immune endpoints.
Assuntos
Dieta Ocidental/efeitos adversos , Hiperglicemia/metabolismo , Hipercinese/metabolismo , Fenóis/toxicidade , Alimentos de Soja/efeitos adversos , Sulfonas/toxicidade , Animais , Glicemia/metabolismo , Dieta Ocidental/psicologia , Disruptores Endócrinos/toxicidade , Feminino , Hiperglicemia/induzido quimicamente , Hiperglicemia/psicologia , Hipercinese/induzido quimicamente , Hipercinese/psicologia , Masculino , Camundongos , Camundongos Endogâmicos NOD , Fitoestrógenos/administração & dosagem , Fitoestrógenos/efeitos adversosRESUMO
Schizophrenia is a mental illness characterized by episodes of psychosis, apathy, social withdrawal, and cognitive impairment. White matter lesions and glutamatergic hypofunction are reported to be the key pathogeneses underlying the multiple clinical symptoms of schizophrenia. Cuprizone (CPZ) is a copper chelator that selectively injures oligodendrocytes, and MK-801 is an antagonist of the N-methyl d-aspartate (NMDA) receptor. To better mimic the psychosis and complicated pathogenesis of schizophrenia, a novel possible mouse model was established by the combination of CPZ and MK-801. After exposure to CPZ for 5 weeks, the mice received a daily intraperitoneal injection of MK-801 for 2-weeks. Behavioral changes in the mouse model were evaluated using Y-maze, object recognition, and open field tests. Pathological changes were observed by transmission electron microscopy, oil red O staining, immunohistochemistry, and western blotting. The results showed that the novel mouse model induced by CPZ plus MK-801 exhibited severe spatial and recognition memory deficits, hyperactivity, and anxiety disorder. Moreover, the mice showed obvious demyelination and white matter damage and decreased expression levels of myelin basic protein (MBP) and 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) in the corpus callosum. Furthermore, the phosphorylation levels of Fyn and NMDA receptor 2B in the corpus callosum and NMDA receptor 1 in the cerebral cortex were noticeably decreased. Taken together, the novel mouse model induced by the combination of cuprizone and MK-801 showed comprehensive behavioral and neurobiological changes, which might make it a suitable animal model for schizophrenia.
Assuntos
Quelantes , Cuprizona , Maleato de Dizocilpina , Esquizofrenia/induzido quimicamente , Psicologia do Esquizofrênico , Animais , Ansiedade/induzido quimicamente , Ansiedade/psicologia , Comportamento Animal , Corpo Caloso/efeitos dos fármacos , Corpo Caloso/metabolismo , Hipercinese/induzido quimicamente , Hipercinese/psicologia , Injeções Intraperitoneais , Masculino , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/psicologia , Camundongos , Camundongos Endogâmicos C57BL , Reconhecimento Psicológico , Esquizofrenia/patologia , Memória Espacial/efeitos dos fármacos , Substância Branca/metabolismo , Substância Branca/patologiaRESUMO
The night shift paradigm induces a state of chronic partial sleep deprivation (CPSD) and enhances the vulnerability to neuronal dysfunction. However, the specific neuronal impact of CPSD has not been thoroughly explored to date. In the current study, the night shift condition was mimicked in female Swiss albino mice. The classical sleep deprivation model, i.e., Modified Multiple Platform (MMP) method, was used for 8 h/day from Monday to Friday with Saturday and Sunday as a weekend off for nine weeks. Following nine weeks of night shift schedule, their neurobehavioral profile and physiological parameters were assessed along with the activity of the mitochondrial complexes, oxidative stress, serotonin levels, and inflammatory markers in the brain. Mice showed an overall hyperactive behavioral profile including hyperlocomotion, aggression, and stereotyped behavior accompanied by decreased activity of mitochondrial enzymes and serotonin levels, increased oxidative stress and inflammatory markers in whole brain homogenates. Collectively, the study points towards the occurrence of a hyperactive behavioral profile akin to mania and psychosis as a potential consequence of CPSD.
Assuntos
Privação do Sono/psicologia , Transtornos do Sono do Ritmo Circadiano/psicologia , Agressão , Animais , Ansiedade/etiologia , Ansiedade/psicologia , Química Encefálica , Doença Crônica , Depressão/etiologia , Depressão/psicologia , Feminino , Hipercinese/etiologia , Hipercinese/psicologia , Mediadores da Inflamação/metabolismo , Camundongos , Mitocôndrias/metabolismo , Atividade Motora , Estresse Oxidativo , Serotonina/metabolismo , Comportamento EstereotipadoRESUMO
RATIONALE: Elevated whole-blood serotonin (5-HT) is a robust biomarker in ~ 30% of patients with autism spectrum disorders, in which repetitive behavior is a core symptom. Furthermore, elevated whole-blood 5-HT has also been described in patients with pediatric obsessive-compulsive disorder. The 5-HT1B receptor is associated with repetitive behaviors seen in both disorders. Chronic blockade of serotonin transporter (SERT) reduces 5-HT1B receptor levels in the orbitofrontal cortex (OFC) and attenuates the sensorimotor deficits and hyperactivity seen with the 5-HT1B agonist RU24969. We hypothesized that enhanced SERT function would increase 5-HT1B receptor levels in OFC and enhance sensorimotor deficits and hyperactivity induced by RU24969. OBJECTIVES: We examined the impact of the SERT Ala56 mutation, which leads to enhanced SERT function, on 5-HT1B receptor binding and 5-HT1B-mediated sensorimotor deficits. METHODS: Specific binding to 5-HT1B receptors was measured in OFC and striatum of naïve SERT Ala56 or wild-type mice. The impact of the 5-HT1A/1B receptor agonist RU24969 on prepulse inhibition (PPI) of startle, hyperactivity, and expression of cFos was examined. RESULTS: While enhanced SERT function increased 5-HT1B receptor levels in OFC of Ala56 mice, RU24969-induced PPI deficits and hyperlocomotion were not different between genotypes. Baseline levels of cFos expression were not different between groups. RU24969 increased cFos expression in OFC of wild-types and decreased cFos in the striatum. CONCLUSIONS: While reducing 5-HT1B receptors may attenuate sensorimotor gating deficits, increased 5-HT1B levels in SERT Ala56 mice do not necessarily exacerbate these deficits, potentially due to compensations during neural circuit development in this model system.
Assuntos
Comportamento Animal/efeitos dos fármacos , Receptor 5-HT1B de Serotonina/efeitos dos fármacos , Receptor 5-HT1B de Serotonina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Substituição de Aminoácidos , Animais , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/metabolismo , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica/fisiologia , Genótipo , Hipercinese/genética , Hipercinese/psicologia , Indóis/farmacologia , Masculino , Camundongos , Mutação/genética , Inibição Pré-Pulso/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/biossíntese , Proteínas Proto-Oncogênicas c-fos/genética , Filtro Sensorial/efeitos dos fármacos , Agonistas do Receptor 5-HT1 de Serotonina/farmacologiaRESUMO
Early life stress is known to impact vulnerability to psychopathological disorders in adulthood, including anxiety and alcohol use disorder (AUD), but the mechanisms underlying susceptibility to these outcomes are not fully understood. In the current study, we used adolescent social isolation (ASI) to determine whether Heterogeneous Stock (HS) rats, an outbred model used for genetic fine-mapping, could be used to study the genetics contributing to ASI-induced anxiety- and AUD-like behavior. We isolated (ASI) or group-housed (adolescent group-housed; AGH) 64 male HS rats at 4 weeks of age. After 5 weeks in these housing conditions, multiple anxiety and coping/despair-like behaviors were measured. All rats were then individually housed and assessed for voluntary ethanol self-administration. At euthanasia, synaptoneurosomes were isolated from a subset of brains to examine the expression of two proteins associated with alcohol drinking-related behaviors, GluA1 and SK2, in the dorsal (dHC) and ventral hippocampus (vHC). We found that ASI increased hyperactivity in the open field test relative to AGH, with no changes in other anxiety-like behaviors. Surprisingly, ASI rats demonstrated decreased immobility and increased climbing in the forced swim test relative to AGH. In contrast to prior studies by us and others, we found no difference in self-administration of 20% ethanol, with decreased ethanol self-administration in ASI relative to AGH rats at higher ethanol concentrations. Furthermore, while ASI in Long-Evans rats resulted in decreased SK2 expression in vHC synaptosomes, no differences were seen in vHC synaptosomes for SK2 or GluA1 in HS rats. These results demonstrate that HS rats are protected against many of the negative effects previously seen in response to ASI, namely anxiety-like behavior and increased ethanol self-administration. The current work suggests that a lack of change in SK2 and GluA1 expression levels in the vHC may play a role in conferring this protection.
Assuntos
Consumo de Bebidas Alcoólicas , Ansiedade , Hipercinese/psicologia , Estresse Psicológico/complicações , Animais , Etanol , Masculino , Ratos , Ratos Long-EvansRESUMO
Hyperactivity is a core ADHD symptom that has been both positively and negatively associated with cognition and functional outcomes. The reason for these conflicting findings is unclear but may relate to subjective assessments that conflate excess physical movement (hyperactivity) with verbally intrusive/impulsive behaviors. The current study adopted a model-driven, rational-empirical approach to distinguish excess physical movement symptoms from other, auditorily perceived behaviors assessed under the "hyperactivity/impulsivity" umbrella. We then tested this alternative conceptualization's fit, reliability, replicability, convergent/divergent validity via actigraphy, and generalizability across informants (parents, teachers) in a well-characterized, clinically evaluated sample of 132 children ages 8-13 years (M = 10.34, SD = 1.51; 47 girls; 67% White/non-Hispanic). The current DSM hyperactivity/impulsivity item pool can be reliably reclassified by knowledgeable judges into items reflecting excess physical movement (visual hyperactivity) and auditory interruptions (verbal intrusion). This bifactor structure showed evidence for multidimensionality and superior model fit relative to traditional hyperactivity/impulsivity models. The resultant visual hyperactivity factor was reliable, replicable, and showed strong convergent validity evidence via associations with objectively assessed hyperactivity. The verbal intrusion factor also showed evidence for reliability and explained a substantive portion of reliable variance, but demonstrated lower estimated replicability. These findings provide preliminary support for conceptualizing ADHD symptoms from the perspective of their cognitive-perceptual impact on others, as well as differentiating excess physical movement (hyperactivity) from other behaviors assessed under the hyperactivity/impulsivity umbrella. "Verbal intrusion" appears to provide a better explanation than "impulsivity" for the reliable, non-hyperactivity variance assessed by these items, but the current item set appears insufficient for replicable measurement of this construct. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Hipercinese/diagnóstico , Comportamento Impulsivo , Percepção , Escalas de Graduação Psiquiátrica , Agitação Psicomotora/diagnóstico , Actigrafia , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Criança , Cognição , Análise Fatorial , Feminino , Humanos , Hipercinese/etiologia , Hipercinese/psicologia , Masculino , Agitação Psicomotora/etiologia , Agitação Psicomotora/psicologia , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: Juvenile myoclonic epilepsy (JME) is the most common genetic generalized epilepsy syndrome. Myoclonus may relate to motor system hyperexcitability and can be provoked by cognitive activities. To aid genetic mapping in complex neuropsychiatric disorders, recent research has utilized imaging intermediate phenotypes (endophenotypes). Here, we aimed to (a) characterize activation profiles of the motor system during different cognitive tasks in patients with JME and their unaffected siblings, and (b) validate those as endophenotypes of JME. METHODS: This prospective cross-sectional investigation included 32 patients with JME, 12 unaffected siblings, and 26 controls, comparable for age, sex, handedness, language laterality, neuropsychological performance, and anxiety and depression scores. We investigated patterns of motor system activation during episodic memory encoding and verb generation functional magnetic resonance imaging (fMRI) tasks. RESULTS: During both tasks, patients and unaffected siblings showed increased activation of motor system areas compared to controls. Effects were more prominent during memory encoding, which entailed hand motion via joystick responses. Subgroup analyses identified stronger activation of the motor cortex in JME patients with ongoing seizures compared to seizure-free patients. Receiver-operating characteristic curves, based on measures of motor activation, accurately discriminated both patients with JME and their siblings from healthy controls (area under the curve: 0.75 and 0.77, for JME and a combined patient-sibling group against controls, respectively; P < .005). SIGNIFICANCE: Motor system hyperactivation represents a cognitive, domain-independent endophenotype of JME. We propose measures of motor system activation as quantitative traits for future genetic imaging studies in this syndrome.
Assuntos
Cognição/fisiologia , Hipercinese/diagnóstico por imagem , Hipercinese/fisiopatologia , Epilepsia Mioclônica Juvenil/diagnóstico por imagem , Epilepsia Mioclônica Juvenil/fisiopatologia , Desempenho Psicomotor/fisiologia , Adolescente , Adulto , Estudos Transversais , Endofenótipos , Feminino , Humanos , Hipercinese/psicologia , Masculino , Pessoa de Meia-Idade , Epilepsia Mioclônica Juvenil/psicologia , Estudos Prospectivos , Adulto JovemRESUMO
Hyperactive/inattentive symptoms (ADHD symptoms) are associated with suicidal behavior in clinical studies, but there is still a lack of population-based longitudinal investigations on the developmental aspects of this association. Additionally, it is unclear whether the association is similar for boys and girls. The objectives of the study were to test the association between the ADHD symptoms during childhood and suicidal ideation and attempt during adolescence, and to investigate sex differences. 1407 children from the Québec Longitudinal Study of Child Development were followed up from 5 months to 17 years of age. We used teacher-reports of ADHD symptoms from 6 to 12 years, and self-report of suicidal ideation and attempt at 13, 15, and 17 years. We identified three ADHD symptoms trajectories: low (boys: 32.2%, girls: 48.7%), moderate (boys: 44.6%; girls: 42.2%) and high (boys: 23.2%; girls: 9.1%). Compared to boys on a low trajectory, boys on a moderate trajectory were at higher risk for suicidal ideation (OR 4.2, 95% CI 1.2-14.8), and boys on a high trajectory were at higher risk for suicide attempts (OR 4.5, 95% CI 1.1-17.9). Girls on moderate or high ADHD symptoms trajectories were not at higher risk for suicidal ideation or attempts than girls on low trajectories. For boys, but not for girls, moderate-to-high ADHD symptoms increased the suicidal risk in adolescence. Interventions with boys showing ADHD symptoms should include a suicide prevention component.
Assuntos
Hipercinese/psicologia , Transtornos Mentais/psicologia , Ideação Suicida , Adolescente , Feminino , Humanos , Estudos Longitudinais , MasculinoRESUMO
Neuroimaging and preclinical studies showing that nicotinic receptors (nAChR) may play a role in mood control has increased interest in targeting the cholinergic system for treatment of major depressive disorder. Indeed, modulation of nAChRs in the basolateral amygdala (BLA) are sufficient to produce an anti-immobility effect in the mouse tail suspension test. However, how α7 nAChR modulation impacts BLA neuronal activity in vivo as well as the downstream mechanisms involved in its mood-related effects are not understood. In this work, we used the unpredictable chronic mild stress (CMS) model to investigate the mechanisms underlying the antidepressant-like effect of an α7 nAChR full agonist on BLA-induced changes in dopaminergic neurotransmission. Male adult Sprague-Dawley rats were exposed to four weeks of CMS. Behavioral and electrophysiological experiments were performed within one week following stress. CMS exposure increased rats' immobility time in the forced swimming test, decreased the number of spontaneously active dopamine neurons in the ventral tegmental area and increased the firing rate of putative projection neurons in the BLA. Stress-induced behavioral and electrophysiological changes were reversed by a single systemic administration of PNU282987. In summary, our findings corroborate previous descriptions of a potential rapid antidepressant effect for the α7 nAChR full agonist. This effect appears to involve a mechanism distinct from those of classic antidepressants: normalization of BLA hyperactivity and, consequently, of DA hypofunction. These observations corroborate the role of α7 nAChR as a potential target for novel antidepressant drug development.
Assuntos
Complexo Nuclear Basolateral da Amígdala/efeitos dos fármacos , Benzamidas/uso terapêutico , Compostos Bicíclicos com Pontes/uso terapêutico , Hipercinese/tratamento farmacológico , Agonistas Nicotínicos/uso terapêutico , Estresse Psicológico/tratamento farmacológico , Receptor Nicotínico de Acetilcolina alfa7/agonistas , Animais , Complexo Nuclear Basolateral da Amígdala/metabolismo , Benzamidas/farmacologia , Compostos Bicíclicos com Pontes/farmacologia , Doença Crônica , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Hipercinese/metabolismo , Hipercinese/psicologia , Masculino , Agonistas Nicotínicos/farmacologia , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/metabolismo , Estresse Psicológico/psicologiaAssuntos
Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtornos da Percepção Auditiva/psicologia , Hipercinese/psicologia , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtornos da Percepção Auditiva/diagnóstico , Criança , Comorbidade , Diagnóstico Diferencial , Manual Diagnóstico e Estatístico de Transtornos Mentais , Estudo de Associação Genômica Ampla/métodos , Humanos , Hipercinese/diagnóstico , Comportamento Impulsivo/fisiologia , Neuroimagem/métodos , FenótipoRESUMO
Signaling of brain-derived neurotrophic factor (BDNF) via tropomyosin receptor kinase B (TrkB) plays a critical role in the maturation of cortical inhibition and controls expression of inhibitory interneuron markers, including the neuropeptide cortistatin (CST). CST is expressed exclusively in a subset of cortical and hippocampal GABAergic interneurons, where it has anticonvulsant effects and controls sleep slow-wave activity (SWA). We hypothesized that CST-expressing interneurons play a critical role in regulating excitatory/inhibitory balance, and that BDNF, signaling through TrkB receptors on CST-expressing interneurons, is required for this function. Ablation of CST-expressing cells caused generalized seizures and premature death during early postnatal development, demonstrating a critical role for these cells in providing inhibition. Mice in which TrkB was selectively deleted from CST-expressing interneurons were hyperactive, slept less and developed spontaneous seizures. Frequencies of spontaneous excitatory post-synaptic currents (sEPSCs) on CST-expressing interneurons were attenuated in these mice. These data suggest that BDNF, signaling through TrkB receptors on CST-expressing cells, promotes excitatory drive onto these cells. Loss of excitatory drive onto CST-expressing cells that lack TrkB receptors may contribute to observed hyperexcitability and epileptogenesis.
Assuntos
Comportamento Animal , Ondas Encefálicas , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Encéfalo/metabolismo , Hipercinese/metabolismo , Interneurônios/metabolismo , Locomoção , Glicoproteínas de Membrana/metabolismo , Neuropeptídeos/metabolismo , Proteínas Tirosina Quinases/metabolismo , Convulsões/metabolismo , Transmissão Sináptica , Animais , Encéfalo/fisiopatologia , Potenciais Pós-Sinápticos Excitadores , Hipercinese/fisiopatologia , Hipercinese/prevenção & controle , Hipercinese/psicologia , Glicoproteínas de Membrana/deficiência , Glicoproteínas de Membrana/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Inibição Neural , Neuropeptídeos/deficiência , Neuropeptídeos/genética , Proteínas Tirosina Quinases/deficiência , Proteínas Tirosina Quinases/genética , Convulsões/fisiopatologia , Convulsões/prevenção & controle , Convulsões/psicologia , SonoRESUMO
As the classroom represents an important social context for the development of out-group attitudes, the current study investigated the role of inclusive classroom norms for students' attitudes toward hyperactive peers. The study included 1209 Swiss children from 61 school classes who were surveyed in the fifth grade (T1) and in the sixth grade (T2) (MageT1â¯=â¯11.55â¯years, MageT2â¯=â¯12.58â¯years). Students' attitudes toward hyperactive children was assessed by self-reports on students' sympathy and intended inclusion toward hypothetical children who show hyperactive behavior. Moreover, students rated their classmates' inclusive attitudes. Analyses with an autoregressive multilevel path model revealed that inclusive classrooms norms in the fifth grade predicted students' sympathy and intended inclusion toward hyperactive children in the sixth grade. The results implicate that group-level analyses are important in order to explain hyperactive children's peer group problems.
Assuntos
Empatia/fisiologia , Hipercinese/psicologia , Relações Interpessoais , Instituições Acadêmicas , Meio Social , Normas Sociais , Estudantes/psicologia , Atitude , Criança , Feminino , Humanos , Masculino , Grupo Associado , Comportamento SocialRESUMO
Group B Streptococcus (GBS) is one the most common bacterium responsible of maternal infections during pregnancy. Offspring in utero-exposed to GBS-induced placental inflammation displayed sex-specific forebrain injuries. Sex differences have been reported in several neuropsychiatric disorders. Hence, we hypothesized that female rats in utero-exposed to GBS may present sex-specific neurobehavioral impairments. Lewis rats were injected intraperitoneally every 12â¯h from gestational day (G) 19 to G22 with either saline (controls) or inactivated serotype Ia GBS (109 CFU). Before puberty, no difference in terms of spontaneous motor activity, exploratory or anxiety-related behaviors was noticed between experimental conditions. During puberty, GBS-exposed females - but not males - performed worse than same-sex controls in a forced motor task. During adulthood, GBS-exposed females - but not males - displayed increased spontaneous locomotor activity and decreased inhibition. In conclusion, our findings show for the first time that adult females - but not males - in utero-exposed to GBS-induced inflammation presented a hyperactive and disinhibited phenotype emerging after puberty.
Assuntos
Hipercinese/etiologia , Hipercinese/psicologia , Efeitos Tardios da Exposição Pré-Natal/psicologia , Infecções Estreptocócicas/psicologia , Streptococcus agalactiae , Animais , Ansiedade/psicologia , Corioamnionite/psicologia , Feminino , Inibição Psicológica , Masculino , Atividade Motora , Equilíbrio Postural , Gravidez , Ratos , Ratos Endogâmicos Lew , Caracteres Sexuais , Maturidade SexualRESUMO
BACKGROUND: It has been suggested that prenatal maternal stress may increase the risk of childhood externalizing disorders, yet no large cohort study has investigated this association across a large range of acute stressors. Our objective was to estimate the association between prenatal stressful events and risk of offspring conduct disorder and hyperactivity. METHODS: We used data from 10,184 mother-offspring pairs from the United Kingdom-based Avon Longitudinal Study of Parents and Children. Mothers self-reported 42 prenatal stressful life events at 18 weeks' gestation. Symptoms of conduct disorder and hyperactivity in their offspring were measured at 6, 9, 11, 13, and 16 years of age using the Strengths and Difficulties Questionnaire. The primary outcome was membership in high-symptom trajectories of 1) conduct disorder and 2) hyperactivity throughout childhood, identified using latent class growth modeling. Multinomial logistic regression models estimated the association between prenatal stress and both conduct disorder and hyperactivity, after adjusting for sex, parental education, low birth weight, preterm birth, parental social class, maternal smoking and drinking, maternal mental health, offspring stressful life events, and offspring depressive and anxious symptoms. RESULTS: Those exposed to the highest quartile of prenatal stress were more likely to belong to the high symptom trajectory for hyperactivity (B = 0.46, p < .05) and conduct disorder (B = 0.88, p < .01), respectively. Prenatal stress further demonstrated a positive, dose-response relationship with symptoms of externalizing disorders at independent time points. CONCLUSIONS: The findings suggest that prenatal stressful events may be an independent risk factor for offspring externalizing symptoms, regardless of maternal mental health and offspring internalizing.
Assuntos
Transtorno da Conduta/etiologia , Hipercinese/etiologia , Mães/psicologia , Efeitos Tardios da Exposição Pré-Natal/psicologia , Estresse Psicológico/complicações , Adolescente , Adulto , Criança , Transtorno da Conduta/psicologia , Feminino , Humanos , Hipercinese/psicologia , Recém-Nascido , Estudos Longitudinais , Gravidez , Estresse Psicológico/psicologia , Inquéritos e QuestionáriosRESUMO
Plasticity related gene 1 (PRG-1) is a neuron specific membrane protein located at the postsynaptic density of glutamatergic synapses. PRG-1 modulates signaling pathways of phosphorylated lipid substrates such as lysophosphatidic acid (LPA). Deletion of PRG-1 increases presynaptic glutamate release probability leading to neuronal over-excitation. However, due to its cortical expression, PRG-1 deficiency leading to increased glutamatergic transmission is supposed to also affect motor pathways. We therefore analyzed the effects of PRG-1 function on exploratory and motor behavior using homozygous PRG-1 knockout (PRG-1-/-) mice and PRG-1/LPA2-receptor double knockout (PRG-1-/-/LPA2-/-) mice in two open field settings of different size and assessing motor behavior in the Rota Rod test. PRG-1-/- mice displayed significantly longer path lengths and higher running speed in both open field conditions. In addition, PRG-1-/- mice spent significantly longer time in the larger open field and displayed rearing and self-grooming behavior. Furthermore PRG-1-/- mice displayed stereotypical behavior resembling phenotypes of psychiatric disorders in the smaller sized open field arena. Altogether, this behavior is similar to the stereotypical behavior observed in animal models for psychiatric disease of autistic spectrum disorders which reflects a disrupted balance between glutamatergic and GABAergic synapses. These differences indicate an altered excitation/inhibition balance in neuronal circuits in PRG-1-/- mice as recently shown in the somatosensory cortex [38]. In contrast, PRG-1-/-/LPA2-/- did not show significant changes in behavior in the open field suggesting that these specific alterations were abolished when the LPA2-receptor was lacking. Our findings indicate that PRG-1 deficiency led to over-excitability caused by an altered LPA/LPA2-R signaling inducing a behavioral phenotype typically observed in animal models for psychiatric disorders.
Assuntos
Proteínas de Ligação a Calmodulina/deficiência , Comportamento Exploratório/fisiologia , Hipercinese/metabolismo , Lisofosfolipídeos/metabolismo , Transtornos Mentais/metabolismo , Proteínas do Tecido Nervoso/deficiência , Receptores de Ácidos Lisofosfatídicos/metabolismo , Sinapses/metabolismo , Animais , Proteínas de Ligação a Calmodulina/genética , Proteínas de Ligação a Calmodulina/metabolismo , Feminino , Ácido Glutâmico/metabolismo , Hipocampo/metabolismo , Hipercinese/genética , Hipercinese/fisiopatologia , Hipercinese/psicologia , Transtornos Mentais/genética , Transtornos Mentais/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Neurônios/fisiologia , Receptores de Ácidos Lisofosfatídicos/genética , Transdução de Sinais , Córtex Somatossensorial/metabolismo , Sinapses/genéticaRESUMO
Bilateral vestibular loss (BVL) causes a unique behavioural syndrome in rodents, with symptoms such as locomotor hyperactivity and changes in exploratory behaviour. Many of these symptoms appear to be indirect consequences of the loss of vestibular reflex function and are difficult to explain. Although such symptoms have been reported before, there have been few systematic studies of the effects of BVL using automated digital tracking systems in which many behavioural symptoms can be measured simultaneously with high precision. In this study, data were obtained from rats with BVL induced by intratympanic sodium arsanilate injections (nâ=â7) or sham injections (nâ=â8) and their behaviour in the open field was measured at 3 days and 23 days post-injection using Ethovision™ tracking software. BVL rats demonstrated reduced thigmotaxis, with more time spent in the central zones. Twenty-three days post-injection, BVL animals showed increased locomotor activity in the open field. The increase in activity was also reflected in the number of transitions between each zone of the field. In addition to increased activity, BVL animals showed increased whole body rotations following lesions. Using linear discriminant analysis (LDA) and random forest classification (RFC), we were able to show that the indirect behavioural effects of BVL, excluding direct measurement of vestibular reflex function, could correctly predict whether animals had received a BVL with a high degree of accuracy at both day 3 and day 23 post-BVL (83% and 100% for LDA, and 100% and 100% for RFC, respectively). RFC has been similarly successful in classifying other hyperactivity syndromes such as attention deficit hyperactivity disorder. These results suggest that BVL results in a unique behavioural signature that can identify vestibular loss in rats even without direct vestibular reflex measurements.
Assuntos
Comportamento Exploratório , Doenças Vestibulares/psicologia , Animais , Ácido Arsanílico , Lateralidade Funcional , Hipercinese/etiologia , Hipercinese/psicologia , Injeções , Masculino , Atividade Motora , Ratos , Ratos Wistar , Reflexo Vestíbulo-Ocular , Rotação , Membrana Timpânica , Doenças Vestibulares/induzido quimicamente , Doenças Vestibulares/complicações , Testes de Função VestibularRESUMO
OBJECTIVE: This study examined relationships between inattentive and hyperactive/impulsive behaviors and working memory (WM) functioning, and the utility of WM in categorical diagnosis of ADHD versus considering ADHD symptoms on a continuum. METHOD: The study included 50 male children (6-12 years). Inattentive and hyperactive/impulsive behaviors were measured by the Conners-3P parent report, and WM was assessed by the WISC-IV WM subtests and Working Memory Index (WMI). RESULTS: WISC-IV Arithmetic and Digit Span Backward were most consistently related to inattentive behaviors, and no WM measure was consistently related to ADHD hyperactive/impulsive behaviors. Arithmetic and Digit Span Backward also accounted for significant variance in inattentive behaviors and ADHD inattention symptoms, respectively. Neither the WMI nor the Arithmetic subtest correctly classified individuals diagnosed with ADHD. CONCLUSION: Measurement of inattentive behaviors on a continuum best characterized relationships between symptoms of ADHD and WM functioning; WM functioning did not have utility in categorical understanding of ADHD.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Hipercinese , Comportamento Impulsivo , Memória de Curto Prazo , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Criança , Comportamento Infantil , Humanos , Hipercinese/diagnóstico , Hipercinese/psicologia , Masculino , Escalas de Graduação Psiquiátrica , Estatística como Assunto , Avaliação de Sintomas/métodos , Escala de Memória de WechslerRESUMO
Phencyclidine (PCP), a noncompetitive N-methyl d-aspartate (NMDA) receptor antagonist, provides the most complete pharmacologic model of schizophrenia in humans and animals. Acute PCP causes hyperlocomotion, disrupts prepulse inhibition (PPI), and increases social avoidance in rats. We have previously shown that repeated treatment with the dopamine (DA) D2-like receptor agonists, quinpirole or ropinirole, prevents agonist-induced PPI disruption. In the present study, we examined whether repeated ropinirole treatment similarly attenuates the effects of PCP in a more complete model of schizophrenia symptoms and examined the effect of repeated D2-like agonist treatment on locomotion, PPI, and social interaction after acute PCP challenge. The acute effect of PCP (3.0 or 6.0 mg/kg) on locomotor activity was examined to establish a minimum effective dose. Thereafter, the effect of PCP challenge (3.0 mg/kg) on locomotor activity, PPI, and social interaction was assessed in adult male rats before or 7-10 days after termination of repeated daily treatment with ropinirole (0.1 mg/kg) or saline vehicle (0.1 ml/kg) for 28 days. Repeated ropinirole treatment attenuates PCP-induced hyperlocomotion, PPI deficits, and social avoidance. These findings suggest that repeated ropinirole treatment might affect a final common pathway that is vulnerable to both PCP- and dopamine agonist-induced behavioral disruption, thereby providing an alternative approach to block the effects of PCP.
Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Hipercinese/induzido quimicamente , Hipercinese/tratamento farmacológico , Indóis/administração & dosagem , Fenciclidina/toxicidade , Inibição Pré-Pulso/efeitos dos fármacos , Animais , Aprendizagem da Esquiva/fisiologia , Agonistas de Dopamina/administração & dosagem , Hipercinese/psicologia , Masculino , Inibição Pré-Pulso/fisiologia , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/fisiologia , Esquizofrenia/induzido quimicamente , Comportamento Social , Resultado do TratamentoRESUMO
Previous research has shown links between parenting and externalizing behavior problems in young children over time. Associations between inhibitory control, one of the executive functions, and externalizing behavior problems are widely established as well. Yet, the role of inhibitory control in the maintenance and change of externalizing behavior problems over time remains unclear. We examined whether inhibitory control could explain the link between mother-child interactions measured on a moment-to-moment timescale and preschoolers' externalizing behavior problems as reported by teachers. With a sample of 173 predominantly clinically referred preschoolers (76.9% boys) we tested a longitudinal model proposing that affective dyadic flexibility and maternal negative affect predict as well as interact in predicting hyperactive/impulsive behavior and aggressive behavior, with preschoolers' inhibitory control as a mediator. Our results provide support for this model for preschoolers' hyperactive/impulsive behavior, but not for aggressive behavior. Hence, inhibitory control is identified as a mechanism linking the content and structure of mother-child interactions to preschoolers' hyperactivity and impulsivity over time.