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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In male rats of the Long-Evans strain, either 7.0 mg/kg of trimethyltin (TMT) or 0.9% NaCl was administered by intragastric gavage. After a period of recovery from the typical signs of trimethyltin toxicity, each rat was tested at 72-hr intervals for its locomotor activity in an open field apparatus, the floor of which was divided into square grids. The baseline activity of each of the trimethyltin-treated rats was significantly greater than the saline-treated controls. d-Amphetamine, injected intraperitoneally in a dose of 0.5 or 2.0 mg/kg, augmented the hyperactivity of the trimethyltin-treated animals. However, a 4.0 mg/kg dose of d-amphetamine markedly attenuated the hyperactivity of trimethyltin-treated rats while elevating that of the controls. Since trimethyltin produced an autism-like behavioral disorder involving hyperactivity, preservation, aggressiveness and impairment in problem-solving and memory function, the placating effect of amphetamine supports the proposition that the pathology due to trimethyltin may represent an experimental analogue to the hyperkinetic syndrome in children.
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PMID:Antagonism by d-amphetamine of trimethyltin-induced hyperactivity evidence toward an animal model of hyperkinetic behavior. 668 32

Twenty-seven infantile autistic children, nine children with other kinds of childhood psychoses, 23 children with mental retardation, and 16 normal children were examined with computerized tomography of the brain. Gross abnormalities were seen in 26% of the autism cases. It was also estimated that about the same proportion of a total population of infantile autistic children show gross changes of CT brain scan. Abnormalities in the region of the frontal horns of the ventricular system tended to be more common in the psychosis groups than in the normal group. Clear-cut right occipital protuberation was rather common in the small group of other psychoses cases but was only marginally more common in the autism than in the normal group. Evans' ratio was significantly higher in all three abnormal groups than in the normal group.
J Autism Dev Disord 1983 Mar
PMID:Childhood psychosis and computed tomographic brain scan findings. 685 37

Offspring of rats exposed to valproic acid (VPA) on gestational day (GD) 12 have been advocated as a rodent model of autism because they show neuron loss in brainstem nuclei and the cerebellum resembling that seen in human autistic cases . Studies of autistic children have reported alterations in acquisition of classical eyeblink conditioning and in reversal of instrumental discrimination learning . Acquisition of discriminative eyeblink conditioning depends on known brainstem-cerebellar circuitry whereas reversal depends on interactions of this circuitry with the hippocampus and prefrontal cortex. In order to explore behavioral parallels of the VPA rodent model with human autism, the present study exposed pregnant Long-Evans rats to 600 mg/kg VPA on GD12 and tested their offspring from Postnatal Day (PND26-31) on discriminative eyeblink conditioning and reversal. VPA rats showed faster eyeblink conditioning, consistent with studies in autistic children . This suggests that previously reported parallels between human autism and the VPA rodent model with respect to injury to brainstem-cerebellar circuitry are accompanied by behavioral parallels when a conditioning task engaging this circuitry is used. VPA rats also showed impaired reversal learning, but this likely reflected "carry-over" of enhanced conditioning during acquisition rather than a reversal learning deficit like that seen in human autism. Further studies of eyeblink conditioning in human autism and in various animal models may help to identify the etiology of this developmental disorder.
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PMID:Discrimination learning and reversal of the conditioned eyeblink reflex in a rodent model of autism. 1713 45

Because there is a strong correlation between tuberous sclerosis and autism, we used a tuberous sclerosis model (Eker rat) to test the hypothesis that these animals would have an altered regional cerebral O2 consumption that might be associated with autism. We also examined whether the altered cerebral O2 consumption was related to changes in the importance of N-methyl-D-aspartate (NMDA) receptors. Young (4 weeks) male control Long Evans (N = 14) and Eker (N = 14) rats (70-100 g) were divided into control and CGS-19755 (10 mg/kg, competitive NMDA antagonist)-treated animals. Cerebral regional blood flow (14C-iodoantipyrine) and O2 consumption (cryomicrospectrophotometry) were determined in isoflurane-anesthetized rats. NMDA receptor protein levels were determined by Western immunoblotting. We found significantly increased basal O2 consumption in the cortex (6.2 +/- 0.6 ml O2/min/100 g Eker vs. 4.7 +/- 0.4 Long Evans), hippocampus, cerebellum, and pons. Regional cerebral blood flow was also elevated in Eker rats at baseline, but cerebral O2 extraction was similar. CGS-19755 significantly lowered O2 consumption in the cortex (2.8 +/- 0.3), hippocampus, and pons of the Long Evans rats but had no effect on cortex (5.8 +/- 0.8) or other regions of the Eker rats. Cerebral blood flow followed a similar pattern. NMDA receptor protein levels (NR1 subunit) were similar between groups. In conclusion, Eker rats had significantly elevated cerebral O2 consumption and blood flow, but this was not related to NMDA receptor activation. In fact, the importance of NMDA receptors in the control of basal cerebral O2 consumption was reduced. This might have important implications in the treatment of autism.
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PMID:Increased cerebral oxygen consumption in Eker rats and effects of N-methyl-D-aspartate blockade: Implications for autism. 1754 50

Since there is a strong correlation between tuberous sclerosis and autism, we used a tuberous sclerosis model (Eker rat) to test the hypothesis that the increased regional cerebral O(2) consumption in the Eker rat might be associated with autism. We also examined whether this increased cerebral O(2) consumption was related to changes in the activity of the gamma-aminobutyric acid (GABA) inhibitory system. Young (4 weeks) male control Long Evans (n=14) and Eker (n=14) rats (70-100g) were divided into control and bicuculline (1mg/kg/min for 2 min then 0.1mg/kg/min for 13 min, GABA(A) receptor antagonist) treated animals. Cerebral regional blood flow ((14)C-iodoantipyrine) and O(2) consumption (cryomicrospectrophotometry) were determined in isoflurane anesthetized rats. We found significantly increased basal O(2) consumption in the cortex (6.3+/-0.7 ml O(2)/min/100g Eker vs. 5.1+/-0.2 ml O(2)/min/100g control), hippocampus and cerebellum, but not the pons. Regional cerebral blood flow was also elevated in the cortex and hippocampus in Eker rats at baseline, but cerebral O(2) extractions were similar. Bicuculline significantly increased O(2) consumption in the cortex (6.5+/-0.3) and all other regions of the control rats, but had no effect on cortex (5.9+/-1.5) or other regions of the Eker rats. Cerebral blood flow followed a similar pattern. In conclusion, Eker rats had significantly elevated cerebral O(2) consumption and blood flow, but this was not affected by GABA receptor blockade. This suggested a reduced activity of the GABA(A) receptor in the brains of Eker rats. This may have important implications in the treatment of autism.
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PMID:Cerebral O(2) consumption in young Eker rats, effects of GABA blockade: implications for autism. 1828 78

Environmental, dietary, and gastrointestinal factors may contribute to autism spectrum disorders (ASD). Propionic acid (PPA) is a short chain fatty acid, a metabolic end-product of enteric bacteria in the gut, and a common food preservative. Recent evidence indicates that PPA can cause behavioral abnormalities and a neuroinflammatory response in rats. Social behavior was examined in similarly-treated pairs of adult male Long-Evans rats placed in an open field following intracerebroventricular (ICV) injection of PPA (4 microl of 0.26 M solution) or control compounds. Behavior was analyzed using both the EthoVision behavior tracking system and by blind scoring of videotapes of social behaviors. Compared to controls, rats treated with PPA displayed social behavior impairments as indicated by significantly greater mean distance apart, reduced time spent in close proximity, reduced playful interaction, and altered responses to playful initiations. Treatment with another short chain fatty acid, sodium acetate, produced similar impairments, but treatment with the alcohol analog of PPA, 1-propanol, did not produce impairments. Immunohistochemical analysis of brain tissue taken from rats treated with PPA revealed reactive astrogliosis, indicating a neuroinflammatory response. These findings suggest that PPA can change both brain and behavior in the laboratory rat in a manner that is consistent with symptoms of human ASD.
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PMID:Intracerebroventricular injection of propionic acid, an enteric bacterial metabolic end-product, impairs social behavior in the rat: implications for an animal model of autism. 1839 59

Rats exposed to valproic acid (VPA) on gestational day 12 (GD12) have been advanced as a rodent model of autism [Arndt TL, Stodgell, Rodier PM. The teratology of autism. Int J Dev Neurosci 2005;23: 189-99.]. These rats show cerebellar anomalies and alterations in eyeblink conditioning that are associated with autism. Autistic humans and VPA-exposed rats show normal responses to conditioned and unconditioned stimuli, but they show marked differences from comparison groups in acquisition, magnitude, and timing of the conditioned response (CR). This study examined VPA-induced eyeblink CR timing differences by training rats on an interstimulus interval (ISI) discrimination task, in which two distinct conditioned stimuli (CS; tone and light) are paired with the same unconditioned stimulus (US; periocular shock) at two distinct CS-US intervals. Previous findings suggest that this task would produce abnormally large and prematurely timed CRs for VPA-exposed rats relative to controls. Adult male Long-Evans rats that were exposed to either VPA or saline on GD 12.5 were trained on an ISI discrimination task [Brown KL, Pagani JH, Stanton ME. The ontogeny of interstimulus interval (ISI) discrimination of the conditioned eyeblink response in rats. Behav Neurosci 2006;120: 1057-70.]. In support of earlier findings, we observed early acquisition and enhanced magnitude of the CR in VPA rats compared with controls on long CS trials. VPA rats also showed prematurely timed CRs to long- CS trials, but not to short- CS trials. The ISI discrimination procedure used in the current study reveals differential timed responses in this animal model of autism not previously seen.
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PMID:Interstimulus interval (ISI) discrimination of the conditioned eyeblink response in a rodent model of autism. 1894 Feb 2

Autism occurs in 1 in 1,000 children and incidence may be increasing. Investigating brain development and developmental injury in humans is difficult. As such, many studies rely on animal models of disorders. We chose to investigate the valproic acid-exposed rat, as this model shares many similarities with autism. Pregnant Long-Evans rats were administered either valproic acid (VPA) or saline during fetal neural tube development. Morphological analyses of cells in layer II of the golgi impregnated motor cortex were done to determine dendritic length, volume, and complexity in both groups. No differences were found in length or volume of cortical dendrites, but dendritic arborization was more complex in apical dendrites of pyramidal cells in VPA-exposed animals than controls. The implication of this finding is that pruning in the VPA-exposed rat is not occurring, which is consistent with theories related to abnormal human brain development in autism.
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PMID:Altered morphology of motor cortex neurons in the VPA rat model of autism. 1898 61

Propionic acid (PPA) is a dietary short chain fatty acid and a metabolic end-product of enteric bacteria. Intracerebroventricular (ICV) injections of PPA can result in brain and behavioral abnormalities in rats similar to those seen in humans suffering from autism. To evaluate cognition and sensorimotor ability in the PPA model, male Long-Evans hooded rats received ICV injection of PPA or control compounds prior to behavioral testing in water maze and beam tasks. Compared to controls, PPA-treated rats were impaired in the water maze task as indicated by an unusual pattern of mild or no impairment during spatial acquisition training, but marked impairment during spatial reversal training. PPA-treated rats were also impaired on the beam task. Neuropathological analysis from PPA-treated rats revealed an innate neuroinflammatory response. These findings add to evidence that PPA can change the brain and behavior in the laboratory rat consistent with symptoms of human autism.
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PMID:Intracerebroventricular injections of the enteric bacterial metabolic product propionic acid impair cognition and sensorimotor ability in the Long-Evans rat: further development of a rodent model of autism. 1915 58

Would you entrust your brain to a bank? Well, many people do after they die, and such brain banks-often funded by government agencies or disease charities-are essential for neuroscience research. They collect and store the healthy and diseased brain specimens that neuroscientists need to explore neurological disorders such as Alzheimer's disease, schizophrenia and autism. Each brain bank typically has a limited supply of samples and tends to operate fairly independently. This means that researchers often have to trawl through numerous brain banks to find their desired specimens. Furthermore, there is a general shortage of brain samples. To help resolve these issues in the UK, James Ironside, professor of clinical neuropathology at the University of Edinburgh, was appointed in June as the director of the new UK Brain Banks Network. An expert in human prion diseases, particularly Creutzfeldt-Jakob disease (CJD), Ironside knows all about brain banks. He established the Brain and Tissue Bank at the UK's National CJD Surveillance Unit and is involved in the Sudden Death Brain and Tissue Bank at the University of Edinburgh. Jon Evans recently caught up with Ironside to discuss his new leadership position and how the brain network will benefit neuroscience research.
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PMID:Straight talk with...James Ironside. [Interviewed by Jon Evans]. 1966 81


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