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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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Alterations of the neuronal nucleus volume deficit throughout the lifespan of subjects diagnosed with autism. Comparison of neuronal nucleus volume (μm3) in 4- to 8-year-old autistic and control subjects revealed significant nucleus volume deficits (blue arrows) in 13 of 16 brain regions examined. In 11- to 23-year-old autistic subjects, the deficit was significant in only two of 16 structures. In 29- to 64-year-old autistic subjects, differences in neuronal nucleus volume were not significant in 10 structures, whereas the volume of nuclei of autistic subjects significantly exceeded the volume of nuclei of control subjects in six other structures (white arrows).
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Fig2: Alterations of the neuronal nucleus volume deficit throughout the lifespan of subjects diagnosed with autism. Comparison of neuronal nucleus volume (μm3) in 4- to 8-year-old autistic and control subjects revealed significant nucleus volume deficits (blue arrows) in 13 of 16 brain regions examined. In 11- to 23-year-old autistic subjects, the deficit was significant in only two of 16 structures. In 29- to 64-year-old autistic subjects, differences in neuronal nucleus volume were not significant in 10 structures, whereas the volume of nuclei of autistic subjects significantly exceeded the volume of nuclei of control subjects in six other structures (white arrows).

Mentions: To detect age-associated changes in neuronal nucleus volume throughout the lifespan of autistic subjects, the volume of nuclei in 16 brain regions in 4- to 8-, 11- to 23-, and 29- to 40-year-old autistic subjects was compared with that of age-matched control subjects (Table 1). Whereas in 4- to 8-year-old autistic children, the nuclear volume deficit was significant in 13 of 16 regions, the number of regions with significant deficits was reduced to only two in 11- to 23-year-old autistic individuals (Table 1, Figure 2), and there was no nuclear volume deficit in 29- to 60-year-old autistic subjects. The increase in neuronal nucleus volume with age in autistic subjects is reflected in the nuclei that were larger than control nuclei in the magnocellular layer of the LGN in 11- to 23-year-old autistic subjects, and the significantly larger neuronal nuclei in six of 16 regions in autistic adults 29– 60 years of age, including the Ammon’s horn, dentate nucleus, magnocellular and parvocellular layers of the LGN, caudate nucleus, and putamen. The increase in the seven other regions did not reach significance. These data indicate that the number of regions with a non-significant difference between the neuronal nucleus volume in autistic and control subjects increased from three in children, to 13 in teenagers/young adults, and ten in older adults.Figure 2


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)

Alterations of the neuronal nucleus volume deficit throughout the lifespan of subjects diagnosed with autism. Comparison of neuronal nucleus volume (μm3) in 4- to 8-year-old autistic and control subjects revealed significant nucleus volume deficits (blue arrows) in 13 of 16 brain regions examined. In 11- to 23-year-old autistic subjects, the deficit was significant in only two of 16 structures. In 29- to 64-year-old autistic subjects, differences in neuronal nucleus volume were not significant in 10 structures, whereas the volume of nuclei of autistic subjects significantly exceeded the volume of nuclei of control subjects in six other structures (white arrows).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig2: Alterations of the neuronal nucleus volume deficit throughout the lifespan of subjects diagnosed with autism. Comparison of neuronal nucleus volume (μm3) in 4- to 8-year-old autistic and control subjects revealed significant nucleus volume deficits (blue arrows) in 13 of 16 brain regions examined. In 11- to 23-year-old autistic subjects, the deficit was significant in only two of 16 structures. In 29- to 64-year-old autistic subjects, differences in neuronal nucleus volume were not significant in 10 structures, whereas the volume of nuclei of autistic subjects significantly exceeded the volume of nuclei of control subjects in six other structures (white arrows).
Mentions: To detect age-associated changes in neuronal nucleus volume throughout the lifespan of autistic subjects, the volume of nuclei in 16 brain regions in 4- to 8-, 11- to 23-, and 29- to 40-year-old autistic subjects was compared with that of age-matched control subjects (Table 1). Whereas in 4- to 8-year-old autistic children, the nuclear volume deficit was significant in 13 of 16 regions, the number of regions with significant deficits was reduced to only two in 11- to 23-year-old autistic individuals (Table 1, Figure 2), and there was no nuclear volume deficit in 29- to 60-year-old autistic subjects. The increase in neuronal nucleus volume with age in autistic subjects is reflected in the nuclei that were larger than control nuclei in the magnocellular layer of the LGN in 11- to 23-year-old autistic subjects, and the significantly larger neuronal nuclei in six of 16 regions in autistic adults 29– 60 years of age, including the Ammon’s horn, dentate nucleus, magnocellular and parvocellular layers of the LGN, caudate nucleus, and putamen. The increase in the seven other regions did not reach significance. These data indicate that the number of regions with a non-significant difference between the neuronal nucleus volume in autistic and control subjects increased from three in children, to 13 in teenagers/young adults, and ten in older adults.Figure 2

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