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Fatemi, S. Hossein; Halt, Amy R; Realmuto, George M.; Earle, Julie; Kist, David A.; Thuras, Paul; Merz, Amelia M.

doi:10.1023/a:1019861721160

Cited by 294 publications

(88 citation statements)

References 3 publications

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“…The involvement of the cerebellum and Purkinje cell dysfunction in autism is a neuro-anatomical measurement that has been explored in humans [28,29,30]. Similar to their findings and other studies using animal models of autism [5,31], we show abnormalities, specifically decreased spine density, in Purkinje cells of the cerebellum.…”

Section: Discussionsupporting

confidence: 89%

Effects of Rat Prenatal Exposure to Valproic Acid on Behaviour and Neuro-Anatomy

et al. 2012

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Autism is a highly debilitating disorder that has recently displayed a dramatic rise in incidence. In order to realistically study preventative and remedial strategies, it is important that we develop and understand useful animal models of the disorder. The purpose of this study was to investigate the efficacy of the prenatal valproic acid (VPA) rat model of autism by examining the neuro-anatomical and behavioural outcomes of offspring exposed to this paradigm. The VPA-treated rats exhibited behavioural changes in the delayed non-match-to-sample task, novel object recognition, activity box, and Whishaw tray reaching task. Anatomically, there was a reduction in brain weight and cortical thickness, along with decreased dendritic branching in the orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC), and decreased spine density in the mPFC, OFC, and cerebellum. Behavioural and anatomical findings from this study produced reliable results indicating that prenatal VPA exposure may be a viable model for the study of autism in rats.

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Section: Discussionsupporting

confidence: 89%

Effects of Rat Prenatal Exposure to Valproic Acid on Behaviour and Neuro-Anatomy

et al. 2012

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“…Third, the two-dimensional Purkinje cell density of normal brain was determined at (16 + 4) cells per mm 2 ( Jeste et al 1984), a value also obtained from our tomographic data. Note, the density of Purkinje cells is reduced by diseases such as schizophrenia, autism, Huntington's disease and other movement disorders ( Jeste et al 1984;Tran et al 1998;Fatemi et al 2002). In summary, there remains no doubt that the micro-features shown in figure 7 are the Purkinje cells, since the location, size, shape and density are very well comparable with the histological results.…”

supporting

confidence: 59%

“…A true measurement of the cell size is therefore impossible. Nevertheless, the spatial resolution of 20 mm, together with the pixel size of 5.1 mm, allows a rough estimate of the diameters of the features detected, which correspond in location and size to the Purkinje cells often visualized in two-dimensional histological slices shown, for instance, in Fatemi et al (2002). Our results agree well with the data of Fatemi et al, who obtained for the cell area (661 + 85) mm 2 from unfixed cerebellar sections but less with the result of stained histological slices by Tran et al (1998), who found (374 + 34) mm 2 .…”

mentioning

confidence: 99%

High-resolution tomographic imaging of a human cerebellum: comparison of absorption and grating-based phase contrast

Schulz

Weitkamp

Zanette

et al. 2010

J. R. Soc. Interface.

144

110

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Human brain tissue belongs to the most impressive and delicate three-dimensional structures in nature. Its outstanding functional importance in the organism implies a strong need for brain imaging modalities. Although magnetic resonance imaging provides deep insights, its spatial resolution is insufficient to study the structure on the level of individual cells. Therefore, our knowledge of brain microstructure currently relies on two-dimensional techniques, optical and electron microscopy, which generally require severe preparation procedures including sectioning and staining. X-ray absorption microtomography yields the necessary spatial resolution, but since the composition of the different types of brain tissue is similar, the images show only marginal contrast. An alternative to absorption could be X-ray phase contrast, which is known for much better discrimination of soft tissues but requires more intricate machinery. In the present communication, we report an evaluation of the recently developed X-ray grating interferometry technique, applied to obtain phase-contrast as well as absorption-contrast synchrotron radiation-based microtomography of human cerebellum. The results are quantitatively compared with synchrotron radiationbased microtomography in optimized absorption-contrast mode. It is demonstrated that grating interferometry allows identifying besides the blood vessels, the stratum moleculare, the stratum granulosum and the white matter. Along the periphery of the stratum granulosum, we have detected microstructures about 40 mm in diameter, which we associate with the Purkinje cells because of their location, size, shape and density. The detection of individual Purkinje cells without the application of any stain or contrast agent is unique in the field of computed tomography and sets new standards in non-destructive three-dimensional imaging.

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“…The study by Fatemi et al [25] of the cerebellum of five males with autism with a mean age of 25.2 years and of five age-matched controls revealed a 24% decrease in mean Purkinje cell size but no differences in Purkinje cell densities. The study of the cerebellum of a 16-year-old female diagnosed with autism and severe intellectual deficit showed no alterations in the cerebellum [24].…”

Section: Discussionmentioning

confidence: 99%

Stereological study of the neuronal number and volume of 38 brain subdivisions of subjects diagnosed with autism reveals significant alterations restricted to the striatum, amygdala and cerebellum

Węgiel

Flory

Kuchna

et al. 2014

acta neuropathol commun

131

109

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IntroductionA total of 38 brain cytoarchitectonic subdivisions, representing subcortical and cortical structures, cerebellum, and brainstem, were examined in 4- to 60-year-old subjects diagnosed with autism and control subjects (a) to detect a global pattern of developmental abnormalities and (b) to establish whether the function of developmentally modified structures matches the behavioral alterations that are diagnostic for autism. The volume of cytoarchitectonic subdivisions, neuronal numerical density, and total number of neurons per region of interest were determined in 14 subjects with autism and 14 age-matched controls by using unbiased stereological methods.ResultsThe study revealed that significant differences between the group of subjects with autism and control groups are limited to a few brain regions, including the cerebellum and some striatum and amygdala subdivisions. In the group of individuals with autism, the total number and numerical density of Purkinje cells in the cerebellum were reduced by 25% and 24%, respectively. In the amygdala, significant reduction of neuronal density was limited to the lateral nucleus (by 12%). Another sign of the topographic selectivity of developmental alterations in the brain of individuals with autism was an increase in the volumes of the caudate nucleus and nucleus accumbens by 22% and 34%, respectively, and the reduced numerical density of neurons in the nucleus accumbens and putamen by 15% and 13%, respectively.ConclusionsThe observed pattern of developmental alterations in the cerebellum, amygdala and striatum is consistent with the results of magnetic resonance imaging studies and their clinical correlations, and of some morphometric studies that indicate that detected abnormalities may contribute to the social and communication deficits, and repetitive and stereotypical behaviors observed in individuals with autism.

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Cited by 294 publications

References 3 publications

Effects of Rat Prenatal Exposure to Valproic Acid on Behaviour and Neuro-Anatomy

Effects of Rat Prenatal Exposure to Valproic Acid on Behaviour and Neuro-Anatomy

High-resolution tomographic imaging of a human cerebellum: comparison of absorption and grating-based phase contrast

Stereological study of the neuronal number and volume of 38 brain subdivisions of subjects diagnosed with autism reveals significant alterations restricted to the striatum, amygdala and cerebellum

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