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. 2003 Dec;23(6):945–952. doi: 10.1023/B:CEMN.0000005322.27203.73

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

Mohsen Araghi-Niknam 1, S Hossein Fatemi 1,2,✉
PMCID: PMC11530152  PMID: 14964781

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.

Keywords: P53, Bcl-2 autism, superior frontal cortex, cerebellum, western blotting

References

  1. Abell, F., et al. (1999). The neuroanatomy of autism. A voxel-based whole brain analysis of structural scans. Neuroreport. 10:1647–1651. [DOI] [PubMed] [Google Scholar]
  2. Afzal, M. A., and Minor, P. D. (2002). Vaccines, Crohn's disease and autism. Mol. Psychiatry7 (Suppl 2):S49-S50. [DOI] [PubMed] [Google Scholar]
  3. Araki, N., et al. (2001). Comparative analysis of brain proteins from P53-deficient mice by two-dimensional electrophoresi. Electrophoresis21:1880–1889. [DOI] [PubMed] [Google Scholar]
  4. Ashcroft, M., and Vousen, K. H. (1999). Regulation of P53 stability. Oncogene13:18(53):7637–7643. [DOI] [PubMed] [Google Scholar]
  5. Barak, Y., et al. (1999). Autistic subjects with comorbid epilepsy: A possible association with viral infections. Child Psychiatry Hum. Dev. 29:(3):245–251. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. 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. [DOI] [PubMed] [Google Scholar]
  8. 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. Psychopharmacology113:487–492. [DOI] [PubMed] [Google Scholar]
  9. Crnic, L. S., (2002). The Colorado mental retardation and developmental disabilities research center. Int. J. Dev. Neurosci. 20(3–5):297–299. [DOI] [PubMed] [Google Scholar]
  10. 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. NeuroReport12:929–933. [DOI] [PubMed] [Google Scholar]
  11. 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. [DOI] [PubMed] [Google Scholar]
  12. 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. Synapse15:281–284. [DOI] [PubMed] [Google Scholar]
  13. 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. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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. Psychiatry52:805–810. [DOI] [PubMed] [Google Scholar]
  15. Gaffney, G. R., et al. (1987). Midsagittal magnetic resonance imaging of autism. Br. J. Psychiatry151:831–833. [DOI] [PubMed] [Google Scholar]
  16. Jarskog. (2000). Cortical Bcl-2 protein—Expression and apoptotic regulation in schizophrenia. Biol. Psychiatry48:641–650. [DOI] [PubMed] [Google Scholar]
  17. Jepsen, R. H., and VonThaden, K. (2002). The effect of cognitive education on the performance of students with neurological developmental disabilities. NeuroRehabilitation17(3):201–209. [PubMed] [Google Scholar]
  18. 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. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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. Brain125:1483–1493. [DOI] [PubMed] [Google Scholar]
  20. Levitt, J. G. (1999). Cerebellar vermis lobules VIII-X in autism. Prog. Neuropsychopharmacol Biol. Psychiatry23:625–633. [DOI] [PubMed] [Google Scholar]
  21. Loveland, K. A., et al. (2001). Judgments of social appropriateness by children and adolescents with autism. J. Autism Dev. Disord. 31:367–376. [DOI] [PubMed] [Google Scholar]
  22. Margolis, R. L. (1997). cDNAs with long CAG trinucleotide repeats from human brain. Hum. Genet. 100:114–122. [DOI] [PubMed] [Google Scholar]
  23. Miyashita, T. (1994). Tumor suppressor P53 is a regulator of Bcl-2 and bax gene expression in vitro and in vivo. Oncogene9:1799–1805. [PubMed] [Google Scholar]
  24. 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. Psychiatry158:1058–1066. [DOI] [PubMed] [Google Scholar]
  25. Piven, J. (1992). Magnetic resonance imaging in autism. Measurement of the cerebellum, pons, and fourth ventricle. Biol. Psychiatry31:491–504. [DOI] [PubMed] [Google Scholar]
  26. 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. Neurology57:1618–1628. [DOI] [PubMed] [Google Scholar]
  27. Rapin, I. (1997). Autism. N. Engl. J Med. 337:97–104. [DOI] [PubMed] [Google Scholar]
  28. Reed, J. C. (1997). Double identity for proteins of the Bcl-2 family. Nature387:773–776. [DOI] [PubMed] [Google Scholar]
  29. Sharova, L. (2000). Nonspecific stimulation of the maternal immune system II. Effects on gene expression in the fetus. Teratology62:420–428. [DOI] [PubMed] [Google Scholar]
  30. Veenstra-Vanderweele, J. (2003). Genetics of childhood disorders: XLVI. Autism, part 5: Genetics of autism. J. Am. Acad. Child Adolesc. Psychiatry42(1):116–118. [DOI] [PubMed] [Google Scholar]
  31. Warren, R. P. (1998). An immunologic theory for the development of some cases of autism. CNS Spectr. 3:71–79. [Google Scholar]
  32. Wing, L. (1997). The autistic spectrum. Lancet350:1761–1766. [DOI] [PubMed] [Google Scholar]

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