Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among 43 female patients aged 17-46 years, most with severe oligophrenia, there were 4 with primary hypogonadism (olfactory-genital dysplasia, Smith-Lemli-Opitz syndrome and lastly a Kanner syndrome). The incidence of genital underdevelopment is assumed to be higher among mentally retarded female patients. In cases of hypogonadism and hypogenitalism a search should always be made for possible mental and neurological disorders.
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PMID:[Primary hypogonadism associated with neuropsychiatric disorders]. 175 40

The suppressive effects of frequent access to olfactory stimulation on the olfactory self-stimulatory behavior of a woman severely disabled by autism were investigated in a noninstitutional community setting. The results indicated that a reduction in self-stimulation could be achieved by frequent presentation of alternative olfactory stimulation, and that direct care staff in a group home setting could successfully apply the strategy. Fourteen months after the onset of treatment the target behavior remained suppressed.
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PMID:Use of similar sensory stimuli in the community-based treatment of self-stimulatory behavior in an adult disabled by autism. 372 96

Numerous studies have implicated oxytocin (OT) and oxytocin receptors in the central mediation of social cognition and social behavior. Much of our understanding of OT's central effects depends on pharmacological studies with OT agonists and antagonists. Recently, our knowledge of OT's effects has been extended by the development of oxytocin knockout (OTKO) mice. Mice with a null mutation of the OT gene manifest several interesting cognitive and behavioral changes, only some of which were predicted by pharmacological studies. Contrary to studies in rats, mice do not appear to require OT for normal sexual or maternal behavior, though OT is necessary for the milk ejection reflex during lactation. OTKO pups thrive if raised by a lactating female, but OTKO pups emit fewer ultrasonic vocalizations with maternal separation and OTKO adults are more aggressive than WT mice. Remarkably, OTKO mice fail to recognize familiar conspecifics after repeated social encounters, though olfactory and non-social memory functions appear to be intact. Central OT administration into the amygdala restores social recognition. The development of transgenic mice with specific deficits in social memory represents a promising approach to examine the cellular and neural systems of social cognition. These studies may provide valuable new perspectives on diseases characterized by social deficits, such as autism or reactive attachment disorder.
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PMID:The social deficits of the oxytocin knockout mouse. 1235 12

The human chromosome 15q11-q13 region is one of the most intriguing imprinted domains, and the abnormalities inherited are associated with neurological disorders including Prader-Willi syndrome (PWS), Angelman syndrome (AS) and autism. Recently we have identified a novel maternally expressed gene, ATP10C, that encodes a putative aminophospholipid translocase within this critical region, 200 kb distal to UBE3A in an imprinted domain on human chromosome 15. ATP10C, with UBE3A, displayed tissue-specific imprinting with predominant expression of the maternal allele in the brain. In this study, we demonstrated that the mouse homologue, Atp10c/pfatp, showed tissue-specific maternal expression in the hippocampus and olfactory bulb, which overlapped the region of imprinted Ube3a expression. These data suggest that the imprinted transcript of Atp10c in the specific region of CNS may be associated with neurological disorders including AS and autism.
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PMID:Predominant maternal expression of the mouse Atp10c in hippocampus and olfactory bulb. 1295 87

The most common genetic cause of mental retardation is Down syndrome, trisomy of chromosome 21, which is accompanied by small stature, developmental delays, and mental retardation. In the Ts65Dn segmental trisomy mouse model of Down syndrome, the section of mouse chromosome 16 most homologous to human chromosome 21 is trisomic. This model exhibits aspects of Down syndrome including growth restriction, delay in achieving developmental milestones, and cognitive dysfunction. Recent data link vasoactive intestinal peptide malfunction with developmental delays and cognitive deficits. Blockage of vasoactive intestinal peptide during rodent development results in growth and developmental delays, neuronal dystrophy, and, in adults, cognitive dysfunction. Also, vasoactive intestinal peptide is elevated in the blood of newborn children with autism and Down syndrome. In the current experiments, vasoactive intestinal peptide binding sites were significantly increased in several brain areas of the segmental trisomy mouse, including the olfactory bulb, hippocampus, cortex, caudate/putamen, and cerebellum, compared with wild-type littermates. In situ hybridization for VIP mRNA revealed significantly more dense vasoactive intestinal peptide mRNA in the hippocampus, cortex, raphe nuclei, and vestibular nuclei in the segmental trisomy mouse compared with wild-type littermates. In the segmental trisomy mouse cortex and hippocampus, over three times as many vasoactive intestinal peptide-immunopositive cells were visible than in wild-type mouse cortex. These abnormalities in vasoactive intestinal peptide parameters in the segmental trisomy model of Down syndrome suggest that vasoactive intestinal peptide may have a role in the neuropathology of Down-like cognitive dysfunction.
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PMID:Vasoactive intestinal peptide in the brain of a mouse model for Down syndrome. 1295 88

Considerable evidence suggests that arginine vasopressin (AVP) is critically involved in the regulation of many social and nonsocial behaviors, including emotionality. The existence of two AVP receptors in the brain, namely the V1a and V1b subtypes, and the lack of clear pharmacological data using selective agonists or antagonists, make it difficult to determine which receptor is responsible for the AVP-mediated effects on behavior. Here we report the behavioral effects of a null mutation in the V1a receptor (V1aR) in male mice. Male mice lacking functional V1aR (V1aRKO) exhibit markedly reduced anxiety-like behavior and a profound impairment in social recognition. V1aRKO performed normally on spatial and nonsocial olfactory learning and memory tasks. Acute central administration of AVP robustly stimulated stereotypical scratching and autogrooming in wild-type (WT), but not V1aRKO males. AVP and oxytocin (OT) mRNA and OT receptor-binding levels were similar in WT and V1aRKO mice. Given the current findings, the V1aR may provide a novel potential pharmacological target for social and affective disorders including autism, and anxiety disorders.
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PMID:Profound impairment in social recognition and reduction in anxiety-like behavior in vasopressin V1a receptor knockout mice. 1464 84

Autism is a severe behavioral disorder characterized by pervasive impairments in social interactions, deficits in verbal and nonverbal communication, and stereotyped, repetitive patterns of behaviors and interests. Recently, a new rodent model of autism was created by exposure of rat fetuses to valproic acid (VPA) on the 12.5th day of gestation (VPA rats). The model has striking anatomical, pathological, and etiological similarities to human data; however, it has not been characterized behaviorally. In order to determine if VPA rats present behavioral aberrations observed in autism, their behavior was extensively evaluated in a battery of tests. The results of the present experiments demonstrate that VPA rats exhibit: (1) lower sensitivity to pain and higher sensitivity to nonpainful stimuli, (2) diminished acoustic prepulse inhibition, (3) locomotor and repetitive/stereotypic-like hyperactivity combined with lower exploratory activity, and (4) decreased number of social behaviors and increased latency to social behaviors. In addition, VPA rats showed delayed maturation, lower body weight, delayed motor development, and attenuated integration of a coordinated series of reflexes, delayed nest-seeking response mediated by olfactory system, and normal negative geotaxis. Interestingly, all behavioral aberrations described in this paper appear before puberty, which could distinguish the VPA rat model of autism from other animal models of neurodevelopmental disorders, especially rodent models of schizophrenia. Our results bring further support to validity of the proposed VPA animal model of autism, suggesting similarities between the observed pattern of behavioral alterations in VPA rats and features of disturbed behavior in autistic patients.
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PMID:Behavioral alterations in rats prenatally exposed to valproic acid: animal model of autism. 1523 91

Rett syndrome (RTT) is a severe neurodevelopmental disorder with features of autism that results from mutation of the gene encoding the transcriptional repressor methyl-CpG binding protein (MECP2). The consequences of loss of a transcription factor may be complex, affecting the expression of many proteins, thus limiting understanding of this class of diseases and impeding therapeutic strategies. This is true for RTT. Neither the cell biological mechanism(s) nor the developmental stage affected by MECP2 deficiency is known. In vivo analysis of the olfactory system demonstrates that Mecp2 deficiency leads to a transient delay in the terminal differentiation of olfactory neurons. This delay in maturation disrupts axonal targeting in the olfactory bulb, resulting in abnormal axonal projections, subglomerular disorganization, and a persistent reduction in glomerular size. These results indicate a critical cell biological function for Mecp2 in mediating the final stages of neuronal development.
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PMID:The transcriptional repressor Mecp2 regulates terminal neuronal differentiation. 1534 42

The olfactory bulb plays a critical role in odor discrimination and in processing olfactory cues controlling social behavior in mammals. Given that the pituitary adenylate cyclase-activating polypeptide (PACAP) type 1 receptor (PAC1) is highly expressed in the olfactory bulb, we examined its role in regulating olfaction and social investigation. We found that olfactory detection of nonsocial stimuli was similar in PAC1-deficient mice and wild-type (WT) littermates. In contrast, PAC1-deficient mice displayed markedly abnormal social behaviors. PAC1-deficient mice exhibited a faster decrease in social investigation after repeated exposure to social cues or ovariectomized female urine compared with WT mice. Moreover, PAC1-deficient females exhibited delayed affiliative behavior when housed with novel males, and PAC1-deficient males displayed excessive sexual mounting toward both females and males as well as reduced aggression and increased licking and grooming toward intruder males. In aggregate, these results uncover PAC1 signaling as an important factor in the development and/or functioning of neural pathways associated with pheromone processing and the regulation of social interactions in mice. In turn, these studies raise the potential clinical relevance of PACAP signaling dysfunctions in neuropsychiatric disorders characterized by social reciprocity impairments such as autism spectrum disorders.
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PMID:Altered social behavior in pituitary adenylate cyclase-activating polypeptide type I receptor-deficient mice. 1547 Jan 44

With optimal pregnancy conditions (natural, enriched diet which includes fish) African (Digo) infants are 3-4 weeks ahead of European/American infants in sensorimotor terms at birth, and during the first year. Infants of semi-aquatic sea-gypsies swim before they walk, and have superior visual acuity compared with us. With adverse pregnancy behaviour (fear of fat, a trend to dieting), neglecting the need for brain fat to secure normal brain development and function, we run a risk of dysfunction--death. Sudden Infant Death Syndrome victims have depressed birth weight, lower levels of marine fat in brainstem than controls, and >80 suffer multiple hypoxic episodes prior to death. Depressed birth weight (more than 10% below mean) is seen in learning and behaviour disorders, and a trend towards weights of less than 3kg is increasing, which supports a rise in antenatal sub optimality. Given marine fat deficiency in pregnancy and infancy, neurons starved for fuel could delay myelination and maturation in the latest developed Frontal Lobes. The phylogenetic oldest Lateral Frontal Lobe System (feed-back mechanism etc.) derived from olfactory bulb-amygdala, which crosses in Anterior Commisure is probably spared, while the Medial Frontal Lobe System derived from Hippocampus-Cingulum and crosses in Corpus Callosum (delayed response task) is most likely affected. The rise in infantile autism (intact vision and hearing) with deficit in delayed response task only, could suggest a deficit in the Medial Frontal Lobe System. The human species is unique; 70% of total energy to the foetus goes to development of the brain, which mainly consists of marine fat. It undergoes pervasive regressive events, before birth, in infancy and at puberty. Minimal retraction of neuronal arborisation is advantageous. Attributable to adverse pregnancy childrearing practice, excessive retraction is likely prenatally and in infancy. Pubertal age affects the fundamental property of nervous tissue, excitability: excessive excitatory drive is seen in early, and a deficiency in late puberty. It is postulated that with adequate marine fat, there is probably no risk of psychopathology at the extremes, whereas a deficiency could lead to paroxysmal (subcortical) dysfunction in early puberty, and breakdown of cortical circuitry and cognitive dysfunctions in late puberty. The post-pubertal psychoses, schizophrenia and manic-depressive psychosis at the extremes of the pubertal age continuum, with contrasting excitability and biological treatment, are probably the result of continuous dietary deficiency, which has inactivated the expression of genes for myelin development and oligodendrocyte-related genes in their production of myelin. The beneficial effect of marine fat in both disorders, in other CNS disorders as well as in developmental dyslexia (DD) and ADHD among others, supports our usual diet is persistently deficient. We have neglected the similarity of our great brain to other mammals, and our marine heritage. Given the amount of marine fat needed to secure normal brain development and function is not known, nor the present dietary level, it seems unduly conjectural to postulate that a dietary deficiency in marine fat is causing brain dysfunction and death. However, all observations point in the same direction: our diet focusing on protein mainly, is deficient, the deficiency is most pronounced in maternal nutrition and in infancy.
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PMID:From superior adaptation and function to brain dysfunction--the neglect of epigenetic factors. 1561 23


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