The Role of Neurodevelopmental Genes in Infectious Etiology of Autism

Autism is a neurodevelopmental disorder with both genetic and environmental etiologies. Prenatal infections may play a role in evolution of autism. Experimental evidence shows human influenza viral infection in pregnancy leads to significant deleterious effects in brain structure and function in the developing mouse progeny. Several brain genes of interest in this animal model are also involved in the pathology of autism. The roles of these genes in brain development are discussed in this review.

[1]  P. Pearl,et al.  The neurobiology of autism: New pieces of the puzzle , 2003, Current neurology and neuroscience reports.

[2]  S. Fatemi,et al.  Reduced Blood Levels of Reelin as a Vulnerability Factor in Pathophysiology of Autistic Disorder , 2002, Cellular and Molecular Neurobiology.

[3]  J. Snaedal,et al.  Ceruloplasmin, superoxide dismutase and copper in autistic patients. , 2005, Basic & clinical pharmacology & toxicology.

[4]  B. Lipska.  CRSN Symposium: Focus on Schizophrenia Symposium du CRSN : le point sur la schizophrénie Using animal models to test a neurodevelopmental hypothesis of schizophrenia , 2004 .

[5]  P. Patterson,et al.  Maternal infection: window on neuroimmune interactions in fetal brain development and mental illness , 2002, Current Opinion in Neurobiology.

[6]  Urs Meyer,et al.  The Time of Prenatal Immune Challenge Determines the Specificity of Inflammation-Mediated Brain and Behavioral Pathology , 2006, The Journal of Neuroscience.

[7]  T. Bourgeron,et al.  Searching for ways out of the autism maze: genetic, epigenetic and environmental clues , 2006, Trends in Neurosciences.

[8]  David A. Pearce,et al.  Reelin signaling is impaired in autism , 2005, Biological Psychiatry.

[9]  N. Bottini,et al.  Autism: evidence of association with adenosine deaminase genetic polymorphism , 2001, Neurogenetics.

[10]  A. Guidotti,et al.  Expression of reelin in adult mammalian blood, liver, pituitary pars intermedia, and adrenal chromaffin cells. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[11]  J. Sanjuán,et al.  Association between FOXP2 polymorphisms and schizophrenia with auditory hallucinations , 2006, Psychiatric genetics.

[12]  A. Minassian,et al.  Sensorimotor Gating Deficits in Adults with Autism , 2007, Biological Psychiatry.

[13]  A. Guidotti,et al.  Reelin is preferentially expressed in neurons synthesizing gamma-aminobutyric acid in cortex and hippocampus of adult rats. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[14]  A. Guidotti,et al.  Colocalization of integrin receptors and reelin in dendritic spine postsynaptic densities of adult nonhuman primate cortex. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[15]  J. Rotrosen,et al.  Impaired prepulse inhibition of acoustic startle in schizophrenia , 2000, Biological Psychiatry.

[16]  A. Brooks,et al.  Prenatal viral infection in mouse causes differential expression of genes in brains of mouse progeny: A potential animal model for schizophrenia and autism , 2005, Synapse.

[17]  Carl Feinstein,et al.  Oxytocin and autistic disorder: alterations in peptide forms , 2001, Biological Psychiatry.

[18]  S. Fatemi,et al.  GABAergic dysfunction in schizophrenia and mood disorders as reflected by decreased levels of glutamic acid decarboxylase 65 and 67 kDa and Reelin proteins in cerebellum , 2005, Schizophrenia Research.

[19]  J. A. Laurence,et al.  Glial fibrillary acidic protein is elevated in superior frontal, parietal and cerebellar cortices of autistic subjects , 2008, The Cerebellum.

[20]  P. Markowitz.  Autism in a child with congenital cytomegalovirus infection , 1983, Journal of autism and developmental disorders.

[21]  K. Mirnics,et al.  Genes and subtypes of schizophrenia. , 2001, Trends in molecular medicine.

[22]  A. Zimmerman,et al.  Neuroglial activation and neuroinflammation in the brain of patients with autism , 2005, Annals of neurology.

[23]  E. Emamian,et al.  Defective corticogenesis and reduction in Reelin immunoreactivity in cortex and hippocampus of prenatally infected neonatal mice , 1999, Molecular Psychiatry.

[24]  Jeffrey K. Yao,et al.  Increased nitric oxide radicals in postmortem brain from patients with schizophrenia. , 2004, Schizophrenia bulletin.

[25]  R. Sidwell,et al.  Glial fibrillary acidic protein and glutamic acid decarboxylase 65 and 67 kDa proteins are increased in brains of neonatal BALB/c mice following viral infection in utero , 2004, Schizophrenia Research.

[26]  H. Bock,et al.  Reelin-mediated Signaling Locally Regulates Protein Kinase B/Akt and Glycogen Synthase Kinase 3β* , 2002, The Journal of Biological Chemistry.

[27]  Limin Shi,et al.  Prenatal Viral Infection Leads to Pyramidal Cell Atrophy and Macrocephaly in Adulthood: Implications for Genesis of Autism and Schizophrenia , 2002, Cellular and Molecular Neurobiology.

[28]  Jing Liu,et al.  Association between the FOXP2 gene and autistic disorder in Chinese population , 2004, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[29]  Paul J. Harrison,et al.  Cellular basis of reduced cortical reelin expression in schizophrenia. , 2006, The American journal of psychiatry.

[30]  S. Faraone,et al.  Hypermethylation of the reelin (RELN) promoter in the brain of schizophrenic patients: A preliminary report , 2005, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[31]  Paul J. Harrison,et al.  Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence , 2005, Molecular Psychiatry.

[32]  Yogesh K. Dwivedi,et al.  Decrease in reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder: a postmortem brain study. , 2000, Archives of general psychiatry.

[33]  Kaoru Takahashi,et al.  Expression of Foxp2, a gene involved in speech and language, in the developing and adult striatum , 2003, Journal of neuroscience research.

[34]  R. Sidwell,et al.  The role of cerebellar genes in pathology of autism and schizophrenia , 2008, The Cerebellum.

[35]  M. Frotscher,et al.  Modulation of Synaptic Plasticity and Memory by Reelin Involves Differential Splicing of the Lipoprotein Receptor Apoer2 , 2005, Neuron.

[36]  R. Murray,et al.  Does prenatal exposure to influenza in mice induce pyramidal cell disarray in the dorsal hippocampus? , 1995, Schizophrenia Research.

[37]  E. G. Stubbs,et al.  Autism and congenital cytomegalovirus , 1984, Journal of autism and developmental disorders.

[38]  D. Falconer.  Two new mutants, ‘trembler’ and ‘reeler’, with neurological actions in the house mouse (Mus musculus L.) , 2008, Journal of Genetics.

[39]  Patrick R Hof,et al.  Neuropathological findings in autism. , 2004, Brain : a journal of neurology.

[40]  S. Schulz,et al.  Glutamic acid decarboxylase 65 and 67 kDa proteins are reduced in autistic parietal and cerebellar cortices , 2002, Biological Psychiatry.

[41]  J. Sutcliffe,et al.  A linkage disequilibrium map of the 1‐Mb 15q12 GABAA receptor subunit cluster and association to autism , 2004, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[42]  W. Brown,et al.  Oxidative stress in autism: increased lipid peroxidation and reduced serum levels of ceruloplasmin and transferrin--the antioxidant proteins. , 2004, Life sciences.

[43]  S. Fatemi,et al.  Dysregulation of Reelin and Bcl-2 Proteins in Autistic Cerebellum , 2001, Journal of autism and developmental disorders.

[44]  S. Chess.  Follow-up report on autism in congenital rubella , 1977, Journal of autism and childhood schizophrenia.

[45]  W. McGinnis.  Oxidative stress in autism. , 2004, Alternative therapies in health and medicine.

[46]  G. D’Arcangelo.  Apoer2: A Reelin Receptor to Remember , 2005, Neuron.

[47]  S. Fatemi,et al.  Reduction in Reelin immunoreactivity in hippocampus of subjects with schizophrenia, bipolar disorder and major depression , 2000, Molecular Psychiatry.

[48]  T. Matsuishi,et al.  Possible Association Between Congenital Cytomegalovirus Infection and Autistic Disorder , 2003, Journal of autism and developmental disorders.

[49]  Yogesh K. Dwivedi,et al.  A decrease of reelin expression as a putative vulnerability factor in schizophrenia. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[50]  A. Guidotti,et al.  Reelin promoter hypermethylation in schizophrenia. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[51]  M. Lubinsky.  Behavioral consequences of congenital rubella. , 1979, The Journal of pediatrics.

[52]  S. Fatemi,et al.  Reelin glycoprotein: structure, biology and roles in health and disease , 2005, Molecular Psychiatry.

[53]  T. Curran,et al.  A protein related to extracellular matrix proteins deleted in the mouse mutant reeler , 1995, Nature.

[54]  Evdokia Anagnostou,et al.  Oxytocin Increases Retention of Social Cognition in Autism , 2007, Biological Psychiatry.

[55]  J. Herz,et al.  Reelin, lipoprotein receptors and synaptic plasticity , 2006, Nature Reviews Neuroscience.

[56]  C. Eberhart,et al.  The Neurobiology of Autism , 2007, Brain pathology.

[57]  Limin Shi,et al.  Maternal Influenza Infection Causes Marked Behavioral and Pharmacological Changes in the Offspring , 2003, The Journal of Neuroscience.

[58]  M. Seike,et al.  The reeler gene-associated antigen on cajal-retzius neurons is a crucial molecule for laminar organization of cortical neurons , 1995, Neuron.