Reduced brainstem size in children with autism

Hashimoto, Toshiaki; Tayama, Masanobu; Miyazaki, Masahito; Sakurama, N; Yoshimoto, Tsutomu; Murakawa, K; Kuroda, Yasuhiro

doi:10.1016/s0387-7604(12)80093-3

Cited by 56 publications

(38 citation statements)

References 19 publications

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“…As mentioned previously, VPA rats also show brain abnormalities resembling those found for autopsy and in brain-imaging studies of autistic patients (Bauman and Kemper, 1985, 1997Gaffney et al, 1988;Hashimoto et al, 1989Hashimoto et al, , 1992Hashimoto et al, , 1995Kemper and Bauman, 1993;Courchesne, 1994Courchesne, , 1997Courchesne, , 2002Rodier et al, 1996Rodier et al, , 1997Ingram et al, 2000). Therefore, VPA rodent model of autism appears to parallel both anatomical and functional pathology reported in autism and related neurodevelopmental disorders confirming validity of the model and its usefulness for further studies.…”

Section: Discussionsupporting

confidence: 80%

“…The 20-24th day of gestation is the time of neural tube closure and development of the first neurons, which form the motor nuclei of the cranial nerves. Histological, anatomical, and MRI studies of nonthalidomide autistic patients' brains confirm existence of very early developmental deficits in this disorder and indicate: (1) abnormalities of the cranial nerve nuclei, (2) hypoplasia of brainstem structures, (3) reduced volume of posterior parts of cerebellar vermis and hemispheres with a loss of Purkinje cells, and (4) injury to deep nuclei of the cerebellum (Bauman and Kemper, 1985, 1997Gaffney et al, 1988;Hashimoto et al, 1989Hashimoto et al, , 1992Hashimoto et al, , 1995Kemper and Bauman, 1993;Courchesne, 1994Courchesne, , 1997Courchesne, , 2002Rodier et al, 1996Rodier et al, , 1997. The absence of gliosis following neuron loss in the described structures suggests that the damage could have occurred only during very early stages of brain development (Sumi and Hager, 1968;Gilles, 1983).…”

Section: Introductionmentioning

confidence: 72%

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Behavioral Alterations in Rats Prenatally Exposed to Valproic Acid: Animal Model of Autism

Schneider

Przewłocki

2004

Neuropsychopharmacol

793

650

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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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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 72%

Behavioral Alterations in Rats Prenatally Exposed to Valproic Acid: Animal Model of Autism

Schneider

Przewłocki

2004

Neuropsychopharmacol

793

650

View full text Add to dashboard Cite

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“…These changes are not dramatic, but with MRimaging techniques reduced brain stem size and especially decreased cerebellar volume can be measured (Hashimoto et al, 1992;Courchesne et al, 1994). Volume reduction was also reported for corpus callosum (Egaas and Courchesne, 1995).…”

Section: Trophic Changesmentioning

confidence: 90%

Can the Pathophysiology of Autism be Explained by the Nature of the Discovered Urine Peptides?

Reichelt¹,

Knivsberg

2003

Nutritional Neuroscience

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Opioid peptides derived from food proteins (exorphins) have been found in urine of autistic patients. Based on the work of several groups, we try to show that exorphins and serotonin uptake stimulating factors may explain many of the signs and symptoms seen in autistic disorders. The individual symptoms ought to be explainable by the properties and behavioural effects of the found peptides. The data presented form the basis of an autism model, where we suggest that exorphins and serotonin uptake modulators are key mediators for the development of autism. This may be due to a genetically based peptidase deficiency in at least two or more peptidases and, or of peptidase regulating proteins made manifest by a dietary overload of exorphin precursors such as by increased gut uptake.

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“…Studies of autistic brain are extremely rare despite pathognomic manifestations in people affected with the disorder. Brain autopsies, albeit of only a few cases, have shown size reduction in brainstem [5] and loss of cellular density of Purkinje Cells in the cerebellum [8]. The other abnormalities include limbic structures and forebrain [1].…”

mentioning

confidence: 99%

Prevalence of serum antibodies to caudate nucleus in autistic children

Singh

Rivas

2004

Neuroscience Letters

101

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Autism may involve autoimmunity to brain. We studied regional distribution of antibodies to rat caudate nucleus, cerebral cortex, cerebellum, brain stem and hippocampus. The study included 30 normal and 68 autistic children. Antibodies were assayed by immunoblotting. Autistic children, but not normal children, had antibodies to caudate nucleus (49% positive sera), cerebral cortex (18% positive sera) and cerebellum (9% positive sera). Brain stem and hippocampus were negative. Antibodies to caudate nucleus were directed towards three proteins having 160, 115 and 49 kD molecular weights. Since a significant number of autistic children had antibodies to caudate nucleus, we propose that an autoimmune reaction to this brain region may cause neurological impairments in autistic children. Thus, the caudate nucleus might be involved in the neurobiology of autism. q 2003 Elsevier Ireland Ltd. All rights reserved.Keywords: Autism; Autoimmunity; Caudate nucleus; Antibodies; Neurobiology Autism is an early-onset disorder of the developing central nervous system (CNS). The disorder causes severe deficits of higher mental functions such as social interaction, language, communication, imagination and cognition. Today, autism is the fastest-growing developmental disability in children. Autism affects more than one-half of a million Americans and millions more worldwide but very little is known about the etiology and pathogenesis of the disorder. Current theories include genetic factors, immune factors, environmental factors and yet other unidentified factors. We focused on immune factors such as autoimmunity and provided supporting evidence for 'autoimmune hypothesis' in autism [9][10][11][12][13][14]. Autoimmunity in autistic children is shown by several autoimmune factors: brain-specific antibodies [10], impaired lymphocyte functions [3,6,[15][16][17], abnormal cytokine regulation [11], viral associations [10,12,13] and indirect association of certain immunogenetic factors [16]. In the present study, our goal was to determine if autistic children harbor brain-specific antibodies, particularly with regards to different brain regions. We selected five brain regions for our study: caudate nucleus (Cn), cerebral cortex (Cx), cerebellum (Cb), brain stem (Bs) and hippocampus (Hpc). Laboratory results described here provide initial evidence for an autoimmune reaction to caudate nucleus in children with autism.The study included 68 autistic children aged 4-12 years and 30 normal children aged 5 -12 years. Of the 68 autistic children, eight had a diagnosis of pervasive developmental disorder (PDD) and the remainder 60 cases had a diagnosis of autism. The clinical diagnosis of autism and/or PDD relied essentially on the standard DSM-IV criteria of the American Association of Psychiatrists, Washington, DC. The Institutional Review Board or the ethical committee of Utah State University reviewed and approved our research protocol that involved the use of blood samples from children. All children were at the baseline without any t...

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Reduced brainstem size in children with autism

Cited by 56 publications

References 19 publications

Behavioral Alterations in Rats Prenatally Exposed to Valproic Acid: Animal Model of Autism

Behavioral Alterations in Rats Prenatally Exposed to Valproic Acid: Animal Model of Autism

Can the Pathophysiology of Autism be Explained by the Nature of the Discovered Urine Peptides?

Prevalence of serum antibodies to caudate nucleus in autistic children

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