Histoanatomic observations of the brain in early infantile autism

Bauman, Margaret L.; Kemper, Thomas L.

doi:10.1212/wnl.35.6.866

Cited by 869 publications

(511 citation statements)

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“…There is also a significant decrease in the number of Purkinje, granule, deep nuclear and inferior olive cells in the En2 mutant [40]. This again is reminiscent of previously reported neuroanatomical abnormalities observed in autistic individuals [10,11].…”

Section: Introductionsupporting

confidence: 84%

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The mouse Engrailed genes: A window into autism

Kuemerle

Gulden

Cherosky

et al. 2007

Behavioural Brain Research

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The complex behavioral symptoms and neuroanatomical abnormalities observed in autistic individuals strongly suggest a multi-factorial basis for this perplexing disease. Although not the perfect model, we believe the Engrailed genes provide an invaluable "window" into the elusive etiology of Autism Spectrum Disorder. The Engrailed-2 gene has been associated with autism in genetic linkage studies. The En2 knock-out mouse harbors cerebellar abnormalities that are similar to those found in autistic individuals and, as we report here, has a distinct anterior shift in the position of the amygdala in the cerebral cortex. Our initial analysis of background effects in the En1 mouse knock-out provides insight as to possible molecular mechanisms and gender differences associated with autism. These findings further the connection between Engrailed and autism and provide new avenues to explore in the ongoing study of the biological basis of this multifaceted disease.

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Section: Introductionsupporting

confidence: 84%

“…Although the neuroanatomical basis of autism is still somewhat unclear, certain brain regions appear to be regularly altered in individuals with ASD. These include areas in the neocortex, cerebellum, amygdala, hippocampus and brain stem [10,11,19].…”

Section: Introductionmentioning

confidence: 99%

The mouse Engrailed genes: A window into autism

Kuemerle

Gulden

Cherosky

et al. 2007

Behavioural Brain Research

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“…Important brain structures for cognitive stress processing, interpretation of stimuli, and triggering of the HPA and autonomous system are the prefrontal cortex and limbic structures like the amygdala (Huether, 1996). In neuroanatomical studies, reduced limbic structure volumes have been found to be correlated to autism (Bauman and Kemper, 1985;Jacobson et al, 1988). The authors have so far not found any specific neuroanatomical studies on autistice-like disorders.…”

Section: Discussionmentioning

confidence: 98%

Differentiation between Autism and Multiple Complex Developmental Disorder in Response to Psychosocial Stress

Jansen

Wied

Gaag

et al. 2002

Neuropsychopharmacol

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Multiple Complex Developmental Disorder (MCDD) represents a distinct group within the autistic spectrum based on symptomatology. Unlike autistic children, part of MCDD children develop schizophrenia in adult life. Despite the differences, patients of both disorders are mainly characterized by abnormal reactions to their social environment. At the biological level, we showed in a previous study that MCDD children have a reduced cortisol response to psychosocial stress. Given the fact that autistic children clinically show more social impairments, it was hypothesized that they may have even further decreased cortisol responses to psychosocial stress than MCDD patients. Therefore, 10 autistic children were compared to 10 MCDD children and 12 healthy control children in their response to a psychosocial stressor, consisting of a public speaking task. In order to test whether any impairments in the biological stress response are specific for psychosocial stress, the autistic children were compared with 11 MCDD children and 15 control children in their response to a physical stressor, consisting of 10 min of bicycle exercise. Heart rate and salivary cortisol levels were used as indicators of response to the stress tests. Autistic children showed a relatively elevated cortisol response to psychosocial stress, in contrast to MCDD children who showed a reduced cortisol response. No differences in heart rate or cortisol responses to the physical stress test were found. The specific difference between autistic and MCDD children in their cortisol response to psychosocial stress indicates that the disturbed reactions to the social environment observed in these disorders may have different biological backgrounds.

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“…-stereotypical behaviors, impaired verbal and nonverbal communication and blunted social interaction) are accompanied by structural and functional changes in cortex, cerebellum and amygdala [3,4,7,8,[19][20][21][22]37,38,49,55,67,101,125]. Structural and functional changes apparent in early childhood suggest that autism is a disorder of brain development [4,19,20,[37][38][39]111].…”

Section: Introductionmentioning

confidence: 99%

Modeling early cortical serotonergic deficits in autism

Boylan

Blue

Höhmann

2007

Behavioural Brain Research

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Autism is a developmental brain disorder characterized by deficits in social interaction, language and behavior. Brain imaging studies demonstrate increased cerebral cortical volumes and micro-and macroscopic neuroanatomic changes in children with this disorder. Alterations in forebrain serotonergic function may underlie the neuroanatomic and behavioral features of autism. Serotonin is involved in neuronal growth and plasticity and these actions are likely mediated via serotonergic and glutamatergic receptors. Few animal models of autism have been described that replicate both etiology and pathophysiology. We report here on a selective serotonin (5-HT) depletion model of this disorder in neonatal mice that mimics neurochemical and structural changes in cortex and, in addition, displays a behavioral phenotype consistent with autism. Newborn male and female mice were depleted of forebrain 5-HT with injections of the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), into the bilateral medial forebrain bundle (mfb). Behavioral testing of these animals as adults revealed alterations in social, sensory and stereotypic behaviors. Lesioned mice showed significantly increased cortical width. Serotonin immunocytochemistry showed a dramatic long-lasting depletion of 5-HT containing fibers in cerebral cortex until postnatal day (PND) 60. Autoradiographic binding to high affinity 5-HT transporters was significantly but transiently reduced in cerebral cortex of 5,7-DHT-depleted mice. AMPA glutamate receptor binding was decreased at PND 15. We hypothesize that increased cerebral cortical volume and sensorimotor, cognitive and social deficits observed in both 5-HT-depleted animals and in individuals with autism, may be the result of deficiencies in timely axonal pruning to key cerebral cortical areas.

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Histoanatomic observations of the brain in early infantile autism

Cited by 869 publications

References 1 publication

The mouse Engrailed genes: A window into autism

The mouse Engrailed genes: A window into autism

Differentiation between Autism and Multiple Complex Developmental Disorder in Response to Psychosocial Stress

Modeling early cortical serotonergic deficits in autism

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