Skip to main content
SpringerLink
Log in

Levels of Bcl-2 and P53 Are Altered in Superior Frontal and Cerebellar Cortices of Autistic Subjects

  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Abstract

1.Autistic disease (AD) is a severe neuropsychiatric disorder affecting 2–4 children per 10,000. We have recently shown reduction of Bcl-2 and increase in P53, two important markers of apoptosis, in parietal cortex of autistic subjects.

2.We hypothesized that brain levels of Bcl-2 and P53 would also be altered in superior frontal cortex and cerebellum of age-, sex, and postmortem-interval (PMI)-matched autistic subjects (N = 5 autistic, N = 4 controls).

3.Brain extracts were prepared from superior frontal cortex and cerebellum and subjected to Western blotting.

4.Results showed that levels of Bcl-2 decreased by 38% and 36% in autistic superior frontal and cerebellar cortices, respectively when compared to control tissues. By the same token, levels of P53 increased by 67.5% and 38% in the same brain areas in autistic subjects vs. controls respectively. Calculations of ratios of Bcl-2/P53 values also decreased by 75% and 43% in autistic frontal and cerebellar cortices vs. controls respectively. The autistic cerebellar values were significantly reduced (p < 0.08) vs. control only. There were no significant differences in levels of β-actin between the two groups. Additionally, there were no correlations between Bcl-2, P53, and β-actin concentrations vs. age or PMI in either group.

5.These results confirm and extend previous data that levels of Bcl-2 and P53 are altered in three important brain tissues, i.e. frontal, parietal, and cerebellar cortices of autistic subjects, alluding to deranged apoptotic mechanisms in autism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abell, F., et al. (1999). The neuroanatomy of autism. A voxel-based whole brain analysis of structural scans. Neuroreport. 10:1647–1651.

    Google Scholar 

  • Afzal, M. A., and Minor, P. D. (2002). Vaccines, Crohn's disease and autism. Mol. Psychiatry 7 (Suppl 2):S49-S50.

    Google Scholar 

  • Araki, N., et al. (2001). Comparative analysis of brain proteins from P53-deficient mice by two-dimensional electrophoresi. Electrophoresis 21:1880–1889.

    Google Scholar 

  • Ashcroft, M., and Vousen, K. H. (1999). Regulation of P53 stability. Oncogene 13:18(53):7637–7643.

    Google Scholar 

  • Barak, Y., et al. (1999). Autistic subjects with comorbid epilepsy: A possible association with viral infections. Child Psychiatry Hum. Dev. 29:(3):245–251.

    Google Scholar 

  • Bauman, M. L., and Kemper, T. L. (1994). Neuroanatomic Observation of the Brain in Autism. The Neurobiology of Autism, John Hopkins University, Baltimore, 119–145.

    Google Scholar 

  • Blatt, G. J., Fitzgerald, C. M., Guptill, J. T., Booker, A. B., Kemper, T. L., and Bauman, M. L. (2001). Density and distribution of hippocampal neurotransmitter receptors in autism: An autoradiographic study. J. Aut. Dev. Dis. 31: 537–543.

    Google Scholar 

  • Bubser, M., and Koch, M. (1994). Prepulse inhibition of the acoustic startle response of rats is reduced by 6-hydroxydopamine lesions of the medial prefrontal cortex. Psychopharmacology 113:487–492.

    Google Scholar 

  • Crnic, L. S., (2002). The Colorado mental retardation and developmental disabilities research center. Int. J. Dev. Neurosci. 20(3–5):297–299.

    Google Scholar 

  • Fatemi, S. H., Halt, A. R., Stary, J. M., Realmuto, G., and Jalali Mousavi, M. (2001a). Reduction in anti-apoptotic protein Bcl-2 in autistic cerebellum. NeuroReport 12:929–933.

    Google Scholar 

  • Fatemi, S. H., Stary, J. M., Halt, A. R., and Realmuto, G. R. (2001b). Dysregulation of Reelin and Bcl-2 proteins in autistic cerebellum. J. Aut. Dev. D. 31:529–534.

    Google Scholar 

  • Fatemi, S. H., and Halt, A. R. (2001). Altered levels of Bcl-2 and P53 proteins in parietal cortex reflect deranged apoptotic regulation in autism. Synapse 15:281–284.

    Google Scholar 

  • Fatemi, S. H., Halt, A. R., Realmuto, G., Kist, D., Earle, J. A., and Thuras, P. (2002a). Reduced Purkinje cell size in autistic cerebellum. Cell Mol. Neurobiol. 22:171–175.

    Google Scholar 

  • Fatemi, S. H., Halt, A. R., Stary, J. M., Kanodia, R., Schulz, S. C., and Realmuto, G. R. (2002b). Glutamic acid decarboxylase 65 and 67 kDa proteins are reduced in autistic parietal and cerebellar cortices. Biol. Psychiatry 52:805–810.

    Google Scholar 

  • Gaffney, G. R., et al. (1987). Midsagittal magnetic resonance imaging of autism. Br. J. Psychiatry 151:831–833.

    Google Scholar 

  • Jarskog. (2000). Cortical Bcl-2 protein—Expression and apoptotic regulation in schizophrenia. Biol. Psychiatry 48:641–650.

    Google Scholar 

  • Jepsen, R. H., and VonThaden, K. (2002). The effect of cognitive education on the performance of students with neurological developmental disabilities. NeuroRehabilitation 17(3):201–209.

    Google Scholar 

  • Lee, R. (2002). The effects of differential and lag reinforcement schedules on varied verbal responding by individuals with autism. J. Appl. Behav. Anal. 35(4):391–402.

    Google Scholar 

  • Lee, M., Martin-Ruiz, C., Graham, A., Court, J., Jaros, E., Perry, R., Iverson, P., Bauman, M., and Perry, E. (2002). Nicotinic receptor adnormalities in the cerebellar cortex in autism. Brain 125:1483–1493.

    Google Scholar 

  • Levitt, J. G. (1999). Cerebellar vermis lobules VIII-X in autism. Prog. Neuropsychopharmacol Biol. Psychiatry 23:625–633.

    Google Scholar 

  • Loveland, K. A., et al. (2001). Judgments of social appropriateness by children and adolescents with autism. J. Autism Dev. Disord. 31:367–376.

    Google Scholar 

  • Margolis, R. L. (1997). cDNAs with long CAG trinucleotide repeats from human brain. Hum. Genet. 100:114–122.

    Google Scholar 

  • Miyashita, T. (1994). Tumor suppressor P53 is a regulator of Bcl-2 and bax gene expression in vitro and in vivo. Oncogene 9:1799–1805.

    Google Scholar 

  • Perry, E. K., Lee, M. L., Martin Ruiz, C. M., and Court, J. A. (2001). Cholinergic activity in autism: Abnormalities in the cerebral cortex and basal forebrain. Am. J. Psychiatry 158:1058–1066.

    Google Scholar 

  • Piven, J. (1992). Magnetic resonance imaging in autism. Measurement of the cerebellum, pons, and fourth ventricle. Biol. Psychiatry 31:491–504.

    Google Scholar 

  • Purcell, A. E., Jeon O. H., Zimmerman, A. W., Blue, M. E., and Pevsner, J. (2001). Postmortem brain abnormalities of the glutamate neurotransmitter system in austim. Neurology 57:1618–1628.

    Google Scholar 

  • Rapin, I. (1997). Autism. N. Engl. J Med. 337:97–104.

    Google Scholar 

  • Reed, J. C. (1997). Double identity for proteins of the Bcl-2 family. Nature 387:773–776.

    Google Scholar 

  • Sharova, L. (2000). Nonspecific stimulation of the maternal immune system II. Effects on gene expression in the fetus. Teratology 62:420–428.

    Google Scholar 

  • Veenstra-Vanderweele, J. (2003). Genetics of childhood disorders: XLVI. Autism, part 5: Genetics of autism. J. Am. Acad. Child Adolesc. Psychiatry 42(1):116–118.

    Google Scholar 

  • Warren, R. P. (1998). An immunologic theory for the development of some cases of autism. CNS Spectr. 3:71–79.

    Google Scholar 

  • Wing, L. (1997). The autistic spectrum. Lancet 350:1761–1766.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neuroscience, Division of Neuroscience Research, University of Minnesota Medical School, Minneapolis, Minnesota, USA

    Mohsen Araghi-Niknam & S. Hossein Fatemi

  2. Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, Minneapolis, Minnesota, USA

    S. Hossein Fatemi

Authors
  1. Mohsen Araghi-Niknam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Hossein Fatemi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. Hossein Fatemi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Araghi-Niknam, M., Fatemi, S.H. Levels of Bcl-2 and P53 Are Altered in Superior Frontal and Cerebellar Cortices of Autistic Subjects. Cell Mol Neurobiol 23, 945–952 (2003). https://doi.org/10.1023/B:CEMN.0000005322.27203.73

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:CEMN.0000005322.27203.73

Search

Navigation