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Neuronal nucleus and cytoplasm volume deficit in children with autism and volume increase in adolescents and adults.

Wegiel J, Flory M, Kuchna I, Nowicki K, Ma SY, Imaki H, Wegiel J, Frackowiak J, Kolecka BM, Wierzba-Bobrowicz T, London E, Wisniewski T, Hof PR, Brown WT - Acta Neuropathol Commun (2015)

Bottom Line: Our data indicate that a deficit of neuronal soma volume in children with autism is associated with deficits in the volume of the neuronal nucleus and cytoplasm.The broad range of functions of the affected structures implies that their developmental and age-associated abnormalities contribute not only to the diagnostic features of autism but also to the broad spectrum of clinical alterations associated with autism.Lack of clinical improvement in autistic teenagers and adults indicates that the observed increase in neuron nucleus and cytoplasm volume close to control level does not normalize brain function.

View Article: PubMed Central - PubMed

ABSTRACT

Introduction: Characterization of the type and topography of structural changes and their alterations throughout the lifespan of individuals with autism is essential for understanding the mechanisms contributing to the autistic phenotype. The aim of this stereological study of neurons in 16 brain structures of 14 autistic and 14 control subjects from 4 to 64 years of age was to establish the course of neuronal nuclear and cytoplasmic volume changes throughout the lifespan of individuals with autism.

Results: Our data indicate that a deficit of neuronal soma volume in children with autism is associated with deficits in the volume of the neuronal nucleus and cytoplasm. The significant deficits of neuronal nuclear and cytoplasmic volumes in 13 of 16 examined subcortical structures, archicortex, cerebellum, and brainstem in 4- to 8-year-old autistic children suggest a global nature of brain developmental abnormalities, but with region-specific differences in the severity of neuronal pathology. The observed increase in nuclear volumes in 8 of 16 structures in the autistic teenagers/young adults and decrease in nuclear volumes in 14 of 16 regions in the age-matched control subjects reveal opposite trajectories throughout the lifespan. The deficit in neuronal nuclear volumes, ranging from 7% to 42% in the 16 examined regions in children with autism, and in neuronal cytoplasmic volumes from 1% to 31%, as well as the broader range of interindividual differences for the nuclear than the cytoplasmic volume deficits, suggest a partial distinction between nuclear and cytoplasmic pathology.

Conclusions: The most severe deficit of both neuronal nucleus and cytoplasm volume in 4-to 8-year-old autistic children appears to be a reflection of early developmental alterations that may have a major contribution to the autistic phenotype. The broad range of functions of the affected structures implies that their developmental and age-associated abnormalities contribute not only to the diagnostic features of autism but also to the broad spectrum of clinical alterations associated with autism. Lack of clinical improvement in autistic teenagers and adults indicates that the observed increase in neuron nucleus and cytoplasm volume close to control level does not normalize brain function.

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Increase of neuronal nuclei volume in teenagers and adults with autism, and decrease in control cohort. Estimates of nucleus volume (μm3) in three age groups of subjects with autism revealed significant increase in eight brain regions (white arrows). In the control cohort, the volume of neurons decreased significantly in 14 regions. The significance level was computed by controlling for post-mortem interval, days of fixation, days of dehydration, and brain weight loss during dehydration. Large arrows indicate a significant difference in both age groups; small arrow marks a significant difference in one of two age groups.
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Fig4: Increase of neuronal nuclei volume in teenagers and adults with autism, and decrease in control cohort. Estimates of nucleus volume (μm3) in three age groups of subjects with autism revealed significant increase in eight brain regions (white arrows). In the control cohort, the volume of neurons decreased significantly in 14 regions. The significance level was computed by controlling for post-mortem interval, days of fixation, days of dehydration, and brain weight loss during dehydration. Large arrows indicate a significant difference in both age groups; small arrow marks a significant difference in one of two age groups.

Mentions: To define the differences between the trajectories of age-associated alterations in neuronal nucleus volume in autism and control subjects, the volume of nuclei has been compared in three age groups within the autistic cohort and within the control cohort. The study revealed opposite trends in autistic and control cohorts (Table 3, Figure 4). The dominant feature of the autistic cohort was the significant increase in the neuronal nucleus volume in eight regions in one of the older groups, including the MBC, thalamus, magno- and parvocellular layers of the LGN, inferior olive, entorhinal cortex, dentate nucleus, and claustrum. The increase observed in six other regions (substantia nigra, Ammon’s horn, amygdala, nucleus, accumbens, caudate nucleus, and putamen) and Purkinje cells in cerebellum did not reach significance. A small but significant decrease of neuronal nucleus volume was found only in the globus pallidus.Table 3


Neuronal nucleus and cytoplasm volume deficit in children with autism and volume increase in adolescents and adults.

Wegiel J, Flory M, Kuchna I, Nowicki K, Ma SY, Imaki H, Wegiel J, Frackowiak J, Kolecka BM, Wierzba-Bobrowicz T, London E, Wisniewski T, Hof PR, Brown WT - Acta Neuropathol Commun (2015)

Increase of neuronal nuclei volume in teenagers and adults with autism, and decrease in control cohort. Estimates of nucleus volume (μm3) in three age groups of subjects with autism revealed significant increase in eight brain regions (white arrows). In the control cohort, the volume of neurons decreased significantly in 14 regions. The significance level was computed by controlling for post-mortem interval, days of fixation, days of dehydration, and brain weight loss during dehydration. Large arrows indicate a significant difference in both age groups; small arrow marks a significant difference in one of two age groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4302585&req=5

Fig4: Increase of neuronal nuclei volume in teenagers and adults with autism, and decrease in control cohort. Estimates of nucleus volume (μm3) in three age groups of subjects with autism revealed significant increase in eight brain regions (white arrows). In the control cohort, the volume of neurons decreased significantly in 14 regions. The significance level was computed by controlling for post-mortem interval, days of fixation, days of dehydration, and brain weight loss during dehydration. Large arrows indicate a significant difference in both age groups; small arrow marks a significant difference in one of two age groups.
Mentions: To define the differences between the trajectories of age-associated alterations in neuronal nucleus volume in autism and control subjects, the volume of nuclei has been compared in three age groups within the autistic cohort and within the control cohort. The study revealed opposite trends in autistic and control cohorts (Table 3, Figure 4). The dominant feature of the autistic cohort was the significant increase in the neuronal nucleus volume in eight regions in one of the older groups, including the MBC, thalamus, magno- and parvocellular layers of the LGN, inferior olive, entorhinal cortex, dentate nucleus, and claustrum. The increase observed in six other regions (substantia nigra, Ammon’s horn, amygdala, nucleus, accumbens, caudate nucleus, and putamen) and Purkinje cells in cerebellum did not reach significance. A small but significant decrease of neuronal nucleus volume was found only in the globus pallidus.Table 3

Bottom Line: Our data indicate that a deficit of neuronal soma volume in children with autism is associated with deficits in the volume of the neuronal nucleus and cytoplasm.The broad range of functions of the affected structures implies that their developmental and age-associated abnormalities contribute not only to the diagnostic features of autism but also to the broad spectrum of clinical alterations associated with autism.Lack of clinical improvement in autistic teenagers and adults indicates that the observed increase in neuron nucleus and cytoplasm volume close to control level does not normalize brain function.

View Article: PubMed Central - PubMed

ABSTRACT

Introduction: Characterization of the type and topography of structural changes and their alterations throughout the lifespan of individuals with autism is essential for understanding the mechanisms contributing to the autistic phenotype. The aim of this stereological study of neurons in 16 brain structures of 14 autistic and 14 control subjects from 4 to 64 years of age was to establish the course of neuronal nuclear and cytoplasmic volume changes throughout the lifespan of individuals with autism.

Results: Our data indicate that a deficit of neuronal soma volume in children with autism is associated with deficits in the volume of the neuronal nucleus and cytoplasm. The significant deficits of neuronal nuclear and cytoplasmic volumes in 13 of 16 examined subcortical structures, archicortex, cerebellum, and brainstem in 4- to 8-year-old autistic children suggest a global nature of brain developmental abnormalities, but with region-specific differences in the severity of neuronal pathology. The observed increase in nuclear volumes in 8 of 16 structures in the autistic teenagers/young adults and decrease in nuclear volumes in 14 of 16 regions in the age-matched control subjects reveal opposite trajectories throughout the lifespan. The deficit in neuronal nuclear volumes, ranging from 7% to 42% in the 16 examined regions in children with autism, and in neuronal cytoplasmic volumes from 1% to 31%, as well as the broader range of interindividual differences for the nuclear than the cytoplasmic volume deficits, suggest a partial distinction between nuclear and cytoplasmic pathology.

Conclusions: The most severe deficit of both neuronal nucleus and cytoplasm volume in 4-to 8-year-old autistic children appears to be a reflection of early developmental alterations that may have a major contribution to the autistic phenotype. The broad range of functions of the affected structures implies that their developmental and age-associated abnormalities contribute not only to the diagnostic features of autism but also to the broad spectrum of clinical alterations associated with autism. Lack of clinical improvement in autistic teenagers and adults indicates that the observed increase in neuron nucleus and cytoplasm volume close to control level does not normalize brain function.

Show MeSH
Related in: MedlinePlus