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Brain-region-specific alterations of the trajectories of neuronal volume growth throughout the lifespan in autism.

Wegiel J, Flory M, Kuchna I, Nowicki K, Ma SY, Imaki H, Wegiel J, Cohen IL, London E, Brown WT, Wisniewski T - Acta Neuropathol Commun (2014)

Bottom Line: The comparative study of the autistic and control subject brains revealed that the number of structures with a significant volume deficit decreased from 14 in the 4- to 8-year-old autistic subjects to 4 in the 36- to 60-year-old.This pattern suggests defects of neuronal growth in early childhood and delayed up-regulation of neuronal growth during adolescence and adulthood reducing neuron soma volume deficit in majority of examined regions.However, significant correction of neuron size but limited clinical improvements suggests that delayed correction does not restore functional deficits.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Developmental Neurobiology, NYS Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA. jerzy.wegiel@opwdd.ny.gov.

ABSTRACT
Several morphometric studies have revealed smaller than normal neurons in the neocortex of autistic subjects. To test the hypothesis that abnormal neuronal growth is a marker of an autism-associated global encephalopathy, neuronal volumes were estimated in 16 brain regions, including various subcortical structures, Ammon's horn, archicortex, cerebellum, and brainstem in 14 brains from individuals with autism 4 to 60 years of age and 14 age-matched control brains. This stereological study showed a significantly smaller volume of neuronal soma in 14 of 16 regions in the 4- to 8-year-old autistic brains than in the controls. Arbitrary classification revealed a very severe neuronal volume deficit in 14.3% of significantly altered structures, severe in 50%, moderate in 21.4%, and mild in 14.3% structures. This pattern suggests desynchronized neuronal growth in the interacting neuronal networks involved in the autistic phenotype. The comparative study of the autistic and control subject brains revealed that the number of structures with a significant volume deficit decreased from 14 in the 4- to 8-year-old autistic subjects to 4 in the 36- to 60-year-old. Neuronal volumes in 75% of the structures examined in the older adults with autism are comparable to neuronal volume in age-matched controls. This pattern suggests defects of neuronal growth in early childhood and delayed up-regulation of neuronal growth during adolescence and adulthood reducing neuron soma volume deficit in majority of examined regions. However, significant correction of neuron size but limited clinical improvements suggests that delayed correction does not restore functional deficits.

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Related in: MedlinePlus

Neuronal soma volume distribution in autistic (red line) and control (green line) subjects in brain structures with the largest neurons (Purkinje cells and neurons in the magnocellular basal complex), moderate size neurons (thalamus and amygdala), and small neurons (caudate nucleus and nucleus accumbens). Graphs show a significant shift towards small size in 4- to 8-year-old autistic subjects in all three neuronal size categories and a rather uniform reduction of differences in volume distribution in 11- to 60-year-old autistic subjects.
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Figure 4: Neuronal soma volume distribution in autistic (red line) and control (green line) subjects in brain structures with the largest neurons (Purkinje cells and neurons in the magnocellular basal complex), moderate size neurons (thalamus and amygdala), and small neurons (caudate nucleus and nucleus accumbens). Graphs show a significant shift towards small size in 4- to 8-year-old autistic subjects in all three neuronal size categories and a rather uniform reduction of differences in volume distribution in 11- to 60-year-old autistic subjects.

Mentions: Figure 4 illustrates the large contribution of smaller neurons in the autistic 4- to 8-year-old subjects in comparison to the controls and the partial or almost complete overlap of the distribution curves in the 11- to 64-year-old subjects. In general, this pattern was similar for large neurons (Purkinje cells and neurons in the magnocellular basal complex), medium-size neurons (thalamus, and amygdala); and small neurons (caudate nucleus and nucleus accumbens).


Brain-region-specific alterations of the trajectories of neuronal volume growth throughout the lifespan in autism.

Wegiel J, Flory M, Kuchna I, Nowicki K, Ma SY, Imaki H, Wegiel J, Cohen IL, London E, Brown WT, Wisniewski T - Acta Neuropathol Commun (2014)

Neuronal soma volume distribution in autistic (red line) and control (green line) subjects in brain structures with the largest neurons (Purkinje cells and neurons in the magnocellular basal complex), moderate size neurons (thalamus and amygdala), and small neurons (caudate nucleus and nucleus accumbens). Graphs show a significant shift towards small size in 4- to 8-year-old autistic subjects in all three neuronal size categories and a rather uniform reduction of differences in volume distribution in 11- to 60-year-old autistic subjects.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4007529&req=5

Figure 4: Neuronal soma volume distribution in autistic (red line) and control (green line) subjects in brain structures with the largest neurons (Purkinje cells and neurons in the magnocellular basal complex), moderate size neurons (thalamus and amygdala), and small neurons (caudate nucleus and nucleus accumbens). Graphs show a significant shift towards small size in 4- to 8-year-old autistic subjects in all three neuronal size categories and a rather uniform reduction of differences in volume distribution in 11- to 60-year-old autistic subjects.
Mentions: Figure 4 illustrates the large contribution of smaller neurons in the autistic 4- to 8-year-old subjects in comparison to the controls and the partial or almost complete overlap of the distribution curves in the 11- to 64-year-old subjects. In general, this pattern was similar for large neurons (Purkinje cells and neurons in the magnocellular basal complex), medium-size neurons (thalamus, and amygdala); and small neurons (caudate nucleus and nucleus accumbens).

Bottom Line: The comparative study of the autistic and control subject brains revealed that the number of structures with a significant volume deficit decreased from 14 in the 4- to 8-year-old autistic subjects to 4 in the 36- to 60-year-old.This pattern suggests defects of neuronal growth in early childhood and delayed up-regulation of neuronal growth during adolescence and adulthood reducing neuron soma volume deficit in majority of examined regions.However, significant correction of neuron size but limited clinical improvements suggests that delayed correction does not restore functional deficits.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Developmental Neurobiology, NYS Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA. jerzy.wegiel@opwdd.ny.gov.

ABSTRACT
Several morphometric studies have revealed smaller than normal neurons in the neocortex of autistic subjects. To test the hypothesis that abnormal neuronal growth is a marker of an autism-associated global encephalopathy, neuronal volumes were estimated in 16 brain regions, including various subcortical structures, Ammon's horn, archicortex, cerebellum, and brainstem in 14 brains from individuals with autism 4 to 60 years of age and 14 age-matched control brains. This stereological study showed a significantly smaller volume of neuronal soma in 14 of 16 regions in the 4- to 8-year-old autistic brains than in the controls. Arbitrary classification revealed a very severe neuronal volume deficit in 14.3% of significantly altered structures, severe in 50%, moderate in 21.4%, and mild in 14.3% structures. This pattern suggests desynchronized neuronal growth in the interacting neuronal networks involved in the autistic phenotype. The comparative study of the autistic and control subject brains revealed that the number of structures with a significant volume deficit decreased from 14 in the 4- to 8-year-old autistic subjects to 4 in the 36- to 60-year-old. Neuronal volumes in 75% of the structures examined in the older adults with autism are comparable to neuronal volume in age-matched controls. This pattern suggests defects of neuronal growth in early childhood and delayed up-regulation of neuronal growth during adolescence and adulthood reducing neuron soma volume deficit in majority of examined regions. However, significant correction of neuron size but limited clinical improvements suggests that delayed correction does not restore functional deficits.

Show MeSH
Related in: MedlinePlus