Skip to main content
Top
Published in: Molecular Autism 1/2017

Open Access 01-12-2017 | Short report

No preliminary evidence of differences in astrocyte density within the white matter of the dorsolateral prefrontal cortex in autism

Authors: Ting Ting Lee, Efstratios Skafidas, Mirella Dottori, Daniela Zantomio, Christos Pantelis, Ian Everall, Gursharan Chana

Published in: Molecular Autism | Issue 1/2017

Login to get access

Abstract

Background

While evidence for white matter and astrocytic abnormalities exist in autism, a detailed investigation of astrocytes has not been conducted. Such an investigation is further warranted by an increasing role for neuroinflammation in autism pathogenesis, with astrocytes being key players in this process. We present the first study of astrocyte density and morphology within the white matter of the dorsolateral prefrontal cortex (DLPFC) in individuals with autism.

Methods

DLPFC formalin-fixed sections containing white matter from individuals with autism (n = 8, age = 4–51 years) and age-matched controls (n = 7, age = 4–46 years) were immunostained for glial fibrillary acidic protein (GFAP). Density of astrocytes and other glia were estimated via the optical fractionator, astrocyte somal size estimated via the nucleator, and astrocyte process length via the spaceballs probe.

Results

We found no evidence for alteration in astrocyte density within DLPFC white matter of individuals with autism versus controls, together with no differences in astrocyte somal size and process length.

Conclusion

Our results suggest that astrocyte abnormalities within the white matter in the DLPFC in autism may be less pronounced than previously thought. However, astrocytic dysregulation may still exist in autism, even in the absence of gross morphological changes. Our lack of evidence for astrocyte abnormalities could have been confounded to an extent by having a small sample size and wide age range, with pathological features potentially restricted to early stages of autism. Nonetheless, future investigations would benefit from assessing functional markers of astrocytes in light of the underlying pathophysiology of autism.
Appendix
Available only for authorised users
Literature
2.
go back to reference Baxter AJ, et al. The epidemiology and global burden of autism spectrum disorders. Psychol Med. 2015;45(3):601–13.CrossRefPubMed Baxter AJ, et al. The epidemiology and global burden of autism spectrum disorders. Psychol Med. 2015;45(3):601–13.CrossRefPubMed
3.
5.
go back to reference Fan LW, Pang Y. Dysregulation of neurogenesis by neuroinflammation: key differences in neurodevelopmental and neurological disorders. Neural Regen Res. 2017;12(3):366–71.CrossRefPubMedPubMedCentral Fan LW, Pang Y. Dysregulation of neurogenesis by neuroinflammation: key differences in neurodevelopmental and neurological disorders. Neural Regen Res. 2017;12(3):366–71.CrossRefPubMedPubMedCentral
6.
go back to reference Panatier A, Robitaille R. Astrocytic mGluR5 and the tripartite synapse. Neuroscience. 2016;323:29–34.CrossRefPubMed Panatier A, Robitaille R. Astrocytic mGluR5 and the tripartite synapse. Neuroscience. 2016;323:29–34.CrossRefPubMed
7.
go back to reference Fiacco TA, McCarthy KD. Astrocyte calcium elevations: properties, propagation, and effects on brain signaling. Glia. 2006;54(7):676–90.CrossRefPubMed Fiacco TA, McCarthy KD. Astrocyte calcium elevations: properties, propagation, and effects on brain signaling. Glia. 2006;54(7):676–90.CrossRefPubMed
8.
9.
go back to reference Moore CS, et al. How factors secreted from astrocytes impact myelin repair. J Neurosci Res. 2011;89(1):13–21.CrossRefPubMed Moore CS, et al. How factors secreted from astrocytes impact myelin repair. J Neurosci Res. 2011;89(1):13–21.CrossRefPubMed
11.
go back to reference Liedtke W, et al. GFAP is necessary for the integrity of CNS white matter architecture and long-term maintenance of myelination. Neuron. 1996;17(4):607–15.CrossRefPubMed Liedtke W, et al. GFAP is necessary for the integrity of CNS white matter architecture and long-term maintenance of myelination. Neuron. 1996;17(4):607–15.CrossRefPubMed
13.
go back to reference Ben Bashat D, et al. Accelerated maturation of white matter in young children with autism: a high b value DWI study. NeuroImage. 2007;37(1):40–7.CrossRefPubMed Ben Bashat D, et al. Accelerated maturation of white matter in young children with autism: a high b value DWI study. NeuroImage. 2007;37(1):40–7.CrossRefPubMed
14.
go back to reference Ouyang M, et al. Atypical age-dependent effects of autism on white matter microstructure in children of 2–7 years. Hum Brain Mapp. 2016;37(2):819–32.CrossRefPubMed Ouyang M, et al. Atypical age-dependent effects of autism on white matter microstructure in children of 2–7 years. Hum Brain Mapp. 2016;37(2):819–32.CrossRefPubMed
15.
go back to reference Herbert MR, et al. Dissociations of cerebral cortex, subcortical and cerebral white matter volumes in autistic boys. Brain. 2003;126(Pt 5):1182–92.CrossRefPubMed Herbert MR, et al. Dissociations of cerebral cortex, subcortical and cerebral white matter volumes in autistic boys. Brain. 2003;126(Pt 5):1182–92.CrossRefPubMed
17.
go back to reference Bigler ED, et al. Volumetric and voxel-based morphometry findings in autism subjects with and without macrocephaly. Dev Neuropsychol. 2010;35(3):278–95.CrossRefPubMedPubMedCentral Bigler ED, et al. Volumetric and voxel-based morphometry findings in autism subjects with and without macrocephaly. Dev Neuropsychol. 2010;35(3):278–95.CrossRefPubMedPubMedCentral
18.
go back to reference Ameis SH, Catani M. Altered white matter connectivity as a neural substrate for social impairment in autism spectrum disorder. Cortex. 2015;62:158–81.CrossRefPubMed Ameis SH, Catani M. Altered white matter connectivity as a neural substrate for social impairment in autism spectrum disorder. Cortex. 2015;62:158–81.CrossRefPubMed
19.
go back to reference Di Martino A, et al. Functional brain correlates of social and nonsocial processes in autism spectrum disorders: an activation likelihood estimation meta-analysis. Biol Psychiatry. 2009;65(1):63–74.CrossRefPubMed Di Martino A, et al. Functional brain correlates of social and nonsocial processes in autism spectrum disorders: an activation likelihood estimation meta-analysis. Biol Psychiatry. 2009;65(1):63–74.CrossRefPubMed
20.
go back to reference Logue SF, Gould TJ. The neural and genetic basis of executive function: attention, cognitive flexibility, and response inhibition. Pharmacol Biochem Behav. 2014;0:45–54.CrossRef Logue SF, Gould TJ. The neural and genetic basis of executive function: attention, cognitive flexibility, and response inhibition. Pharmacol Biochem Behav. 2014;0:45–54.CrossRef
21.
go back to reference Sawa T, et al. Dysfunction of orbitofrontal and dorsolateral prefrontal cortices in children and adolescents with high-functioning pervasive developmental disorders. Ann General Psychiatry. 2013;12:31.CrossRef Sawa T, et al. Dysfunction of orbitofrontal and dorsolateral prefrontal cortices in children and adolescents with high-functioning pervasive developmental disorders. Ann General Psychiatry. 2013;12:31.CrossRef
22.
go back to reference Fujii E, et al. Function of the frontal lobe in autistic individuals<BR>: a proton magnetic resonance spectroscopic study. J Med Investig. 2010;57(1,2):35–44.CrossRef Fujii E, et al. Function of the frontal lobe in autistic individuals<BR>: a proton magnetic resonance spectroscopic study. J Med Investig. 2010;57(1,2):35–44.CrossRef
23.
go back to reference Christakou A, et al. Disorder-specific functional abnormalities during sustained attention in youth with attention deficit hyperactivity disorder (ADHD) and with autism. Mol Psychiatry. 2013;18(2):236–44.CrossRefPubMed Christakou A, et al. Disorder-specific functional abnormalities during sustained attention in youth with attention deficit hyperactivity disorder (ADHD) and with autism. Mol Psychiatry. 2013;18(2):236–44.CrossRefPubMed
24.
go back to reference Purcell AE, et al. Postmortem brain abnormalities of the glutamate neurotransmitter system in autism. Neurology. 2001;57(9):1618–28.CrossRefPubMed Purcell AE, et al. Postmortem brain abnormalities of the glutamate neurotransmitter system in autism. Neurology. 2001;57(9):1618–28.CrossRefPubMed
25.
go back to reference Vargas DL, et al. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol. 2005;57(1):67–81.CrossRefPubMed Vargas DL, et al. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol. 2005;57(1):67–81.CrossRefPubMed
26.
go back to reference Laurence JA, Fatemi SH. Glial fibrillary acidic protein is elevated in superior frontal, parietal and cerebellar cortices of autistic subjects. Cerebellum. 2005;4(3):206–10.CrossRefPubMed Laurence JA, Fatemi SH. Glial fibrillary acidic protein is elevated in superior frontal, parietal and cerebellar cortices of autistic subjects. Cerebellum. 2005;4(3):206–10.CrossRefPubMed
27.
28.
go back to reference Crawford JD, et al. Elevated GFAP protein in anterior cingulate cortical white matter in males with autism spectrum disorder. Autism Res. 2015;8(6):649–57.CrossRefPubMed Crawford JD, et al. Elevated GFAP protein in anterior cingulate cortical white matter in males with autism spectrum disorder. Autism Res. 2015;8(6):649–57.CrossRefPubMed
29.
go back to reference Morgan JT, et al. Stereological study of amygdala glial populations in adolescents and adults with autism spectrum disorder. PLoS One. 2014;9(10):e110356.CrossRefPubMedPubMedCentral Morgan JT, et al. Stereological study of amygdala glial populations in adolescents and adults with autism spectrum disorder. PLoS One. 2014;9(10):e110356.CrossRefPubMedPubMedCentral
30.
go back to reference Fatemi SH, et al. Expression of astrocytic markers aquaporin 4 and connexin 43 is altered in brains of subjects with autism. Synapse. 2008;62(7):501–7.CrossRefPubMedPubMedCentral Fatemi SH, et al. Expression of astrocytic markers aquaporin 4 and connexin 43 is altered in brains of subjects with autism. Synapse. 2008;62(7):501–7.CrossRefPubMedPubMedCentral
31.
go back to reference Kimelberg HK. Functions of mature mammalian astrocytes: a current view. Neuroscientist. 2010;16(1):79–106.CrossRefPubMed Kimelberg HK. Functions of mature mammalian astrocytes: a current view. Neuroscientist. 2010;16(1):79–106.CrossRefPubMed
32.
go back to reference Zantomio D, et al. Convergent evidence for mGluR5 in synaptic and neuroinflammatory pathways implicated in ASD. Neurosci Biobehav Rev. 2015;52:172–7.CrossRefPubMed Zantomio D, et al. Convergent evidence for mGluR5 in synaptic and neuroinflammatory pathways implicated in ASD. Neurosci Biobehav Rev. 2015;52:172–7.CrossRefPubMed
33.
go back to reference Chana G, et al. Decreased expression of mGluR5 within the dorsolateral prefrontal cortex in autism and increased microglial number in mGluR5 knockout mice: pathophysiological and neurobehavioral implications. Brain Behav Immun. 2015;49:197–205.CrossRefPubMed Chana G, et al. Decreased expression of mGluR5 within the dorsolateral prefrontal cortex in autism and increased microglial number in mGluR5 knockout mice: pathophysiological and neurobehavioral implications. Brain Behav Immun. 2015;49:197–205.CrossRefPubMed
34.
35.
go back to reference Gupta S, et al. Transcriptome analysis reveals dysregulation of innate immune response genes and neuronal activity-dependent genes in autism. Nat Commun. 2014;5(2041–1723 (Electronic)):5748.CrossRefPubMedPubMedCentral Gupta S, et al. Transcriptome analysis reveals dysregulation of innate immune response genes and neuronal activity-dependent genes in autism. Nat Commun. 2014;5(2041–1723 (Electronic)):5748.CrossRefPubMedPubMedCentral
36.
go back to reference Gundersen HJ, et al. The efficiency of systematic sampling in stereology—reconsidered. J Microsc. 1999;193(Pt 3):199–211.CrossRefPubMed Gundersen HJ, et al. The efficiency of systematic sampling in stereology—reconsidered. J Microsc. 1999;193(Pt 3):199–211.CrossRefPubMed
38.
39.
go back to reference Lin C.L., et al., Glutamate transporter EAAT2: a new target for the treatment of neurodegenerative diseases. 2012; (1756–8927 (Electronic)). Lin C.L., et al., Glutamate transporter EAAT2: a new target for the treatment of neurodegenerative diseases. 2012; (1756–8927 (Electronic)).
41.
go back to reference Stevens, B., et al., The classical complement cascade mediates CNS synapse elimination. (0092–8674 (Print)). Stevens, B., et al., The classical complement cascade mediates CNS synapse elimination. (0092–8674 (Print)).
42.
go back to reference Ameis, S.H. and M. Catani, Altered white matter connectivity as a neural substrate for social impairment in autism spectrum disorder. 2015; (1973–8102 (Electronic)). Ameis, S.H. and M. Catani, Altered white matter connectivity as a neural substrate for social impairment in autism spectrum disorder. 2015; (1973–8102 (Electronic)).
43.
go back to reference Li T, Giaume Fau–Xiao C, and L. Xiao, Connexins-mediated glia networking impacts myelination and remyelination in the central nervous system. 2014(1559–1182 (Electronic)). Li T, Giaume Fau–Xiao C, and L. Xiao, Connexins-mediated glia networking impacts myelination and remyelination in the central nervous system. 2014(1559–1182 (Electronic)).
45.
go back to reference Lange N, et al. Longitudinal volumetric brain changes in autism Spectrum disorder ages 6–35 years. Autism Res. 2015;8(1):82–93.CrossRefPubMed Lange N, et al. Longitudinal volumetric brain changes in autism Spectrum disorder ages 6–35 years. Autism Res. 2015;8(1):82–93.CrossRefPubMed
46.
go back to reference Hazlett HC, et al. Early brain overgrowth in autism associated with an increase in cortical surface area before age 2. Arch Gen Psychiatry. 2011;68(5):467–76.CrossRefPubMedPubMedCentral Hazlett HC, et al. Early brain overgrowth in autism associated with an increase in cortical surface area before age 2. Arch Gen Psychiatry. 2011;68(5):467–76.CrossRefPubMedPubMedCentral
48.
go back to reference Steinhäuser C, Grunnet M, Carmignoto G. Crucial role of astrocytes in temporal lobe epilepsy. Neuroscience. 2016;323:157–69.CrossRefPubMed Steinhäuser C, Grunnet M, Carmignoto G. Crucial role of astrocytes in temporal lobe epilepsy. Neuroscience. 2016;323:157–69.CrossRefPubMed
Metadata
Title
No preliminary evidence of differences in astrocyte density within the white matter of the dorsolateral prefrontal cortex in autism
Authors
Ting Ting Lee
Efstratios Skafidas
Mirella Dottori
Daniela Zantomio
Christos Pantelis
Ian Everall
Gursharan Chana
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Molecular Autism / Issue 1/2017
Electronic ISSN: 2040-2392
DOI
https://doi.org/10.1186/s13229-017-0181-5

Other articles of this Issue 1/2017

Molecular Autism 1/2017 Go to the issue