Dysregulation of Reelin'Dysregulation of Reelin and Bcl-2 proteins in autistic cerebellum.'
www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ui
ds=11814262&dopt=Abstract
Fatemi SH, Stary JM, Halt AR, Realmuto GR.
Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, Minneapolis 55455, USA. fatem002@tc.umn.edu
Autism is a severe neurodevelopmental disorder with potential genetic and environmental causes. Cerebellar pathology including Purkinje cell atrophy has been demonstrated previously. We hypothesized that cell migration and apoptotic mechanisms may account for observed Purkinje cell abnormalities. Reelin is an important secretory glycoprotein responsible for normal layering of the brain. Bcl-2 is a regulatory protein responsible for control
of programmed cell death in the brain. Autistic and normal control cerebellar corteces matched for age, sex, and post-mortem interval (PMI) were prepared for SDS-gel electrophoresis and
Western blotting using specific anti-Reelin and anti-Bcl-2 antibodies. Quantification of Reelin bands showed 43%, 44%, and 44% reductions in autistic cerebellum (mean optical density +/- SD per 30 microg protein 4.05 +/- 4.0, 1.98 +/- 2.0, 13.88 +/- 11.9 for 410 kDa, 330 kDa, and 180 kDa bands, respectively; N = 5) compared with controls (mean optical density +/-
SD per 30 microg protein, 7.1 +/- 1.6, 3.5 +/- 1.0, 24.7 +/- 5.0; N = 8, p <0.0402 for 180 kDa band). Quantification of Bcl-2 levels showed a 34% to 51% reduction in autistic cerebellum (M +/- SD per 75 microg protein 0.29 +/- 0.08; N = 5) compared with controls (M +/- SD per 75 microg protein 0.59 +/- 0.31; N = 8, p < 0.0451). Measurement of beta-actin (M +/- SD for controls 7.3 +/- 2.9; for autistics 6.77 +/- 0.66) in the same homogenates did not differ
significantly between groups. These results demonstrate for the first time that dysregulation of Reelin and Bcl-2 may be responsible for some of the brain structural and behavioral abnormalities observed in autism.
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November 2001
Glutamate Neurotransmitter System Abnormalities In Autism
Postmortem brain abnormalities of the glutamate neurotransmitter system in autism - Click here
Purcell AE, Jeon OH, Zimmerman AW, Blue ME, Pevsner J. Departments of Neurology (Drs. Jeon, Zimmerman, and Pevsner and A.E. Purcell) and Neuroscience (Dr. Blue), Kennedy Krieger Institute, and the Departments of Neuroscience (Drs. Jeon, Blue, and Pevsner and A.E. Purcell) and Neurology (Dr. Blue), Johns Hopkins University School of Medicine, Baltimore, MD.
BACKGROUND: Studies examining the brains of individuals with autism have identified anatomic and pathologic changes in regions such as the cerebellum and hippocampus. Little, if anything, is known, however, about the molecules that are involved in the pathogenesis of this disorder.
OBJECTIVE: To identify genes with abnormal expression levels in the cerebella of subjects with autism.
METHOD: Brain samples from a total of 10 individuals with autism and 23 matched controls were collected, mainly from the cerebellum. Two cDNA microarray technologies were used to identify genes that were significantly up- or downregulated in autism. The abnormal mRNA or protein levels of several genes identified by microarray analysis were investigated using PCR
with reverse transcription and Western blotting alpha-Amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA)- and NMDA-type glutamate receptor densities were examined with receptor autoradiography in the cerebellum, caudate-putamen, and prefrontal cortex.
RESULTS: The mRNA levels of several genes were significantly increased in autism, including excitatory amino acid transporter 1 and glutamate receptor AMPA 1, two members of the glutamate system. Abnormalities in the protein or mRNA levels of several additional molecules in the glutamate system were identified on further analysis, including glutamate receptor
binding proteins. AMPA-type glutamate receptor density was decreased in the cerebellum of individuals with autism (p < 0.05).
CONCLUSIONS: Subjects with autism may have specific abnormalities in the AMPA-type glutamate receptors and glutamate transporters in the cerebellum. These abnormalities may be directly involved in the pathogenesis of the disorder.
PMID: 11706102 [PubMed - as supplied by publisher] .
September 2001
Plasma Fatty Acid Levels In Autistic Children
Journal: Prostaglandins Leukot Essent Fatty Acids 2001 Jul;65(1):1-7
Vancassel S, Durand G, Barthelemy C, Lejeune B, Martineau J, Guilloteau D, Andres C, Chalon S.
Laboratoire de Nutrition et Securite Alimentaire, INRA, domaine de Vilvert, Jouy-en-Josas
Phospholipid fatty acids are major structural components of neuronal cell membranes, which modulate membrane fluidity and hence function. Evidence from clinical and biochemical sources have indicated changes in the metabolism of fatty acids in several psychiatric disorders. We examined the phospholipid fatty acids in the plasma of a population of autistic subjects compared to mentally retarded controls. Our results showed a marked reduction in the levels of 22: 6n-3 (23%) in the autistic subjects, resulting in significantly lower levels of total (n-3) polyunsaturated fatty acids (PUFA) (20%), without significant reduction in the (n-6) PUFA series, and consequently a significant increase in the (n-6)/(n-3) ratio (25%). These variations are discussed in terms of potential differences in PUFA dietary intake, metabolism, or incorporation into cellular membranes between the two groups of subjects. These results open up interesting perspectives for the investigation of new biological indices in autism. Moreover, this might have new therapeutic implications in terms of child nutrition. Copyright 2001 Harcourt Publishers Ltd.
PMID: 11487301 [PubMed - in process]
Taken from the National Library of Medicine, PubMed database.
