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Abha Chauhan - One of the best experts on this subject based on the ideXlab platform.
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Brain region-specific decrease in the activity and expression of protein kinase A in the frontal cortex of Regressive Autism. PLoS One 2011; 6: e23751
2013Co-Authors: Ved Chauhan, Michael J. Flory, Abha ChauhanAbstract:Autism is a severe neurodevelopmental disorder that is characterized by impaired language, communication, and social skills. In Regressive Autism, affected children first show signs of normal social and language development but eventually lose these skills and develop autistic behavior. Protein kinases are essential in G-protein-coupled, receptor-mediated signal transduction and are involved in neuronal functions, gene expression, memory, and cell differentiation. We studied the activity and expression of protein kinase A (PKA), a cyclic AMP–dependent protein kinase, in postmortem brain tissue samples from the frontal, temporal, parietal, and occipital cortices, and the cerebellum of individuals with Regressive Autism; autistic subjects without a clinical history of regression; and age-matched developmentally normal control subjects. The activity of PKA and the expression of PKA (C-a), a catalytic subunit of PKA, were significantly decreased in the frontal cortex of individuals with Regressive Autism compared to control subjects and individuals with non-Regressive Autism. Such changes were not observed in the cerebellum, or the cortices from the temporal, parietal, and occipital regions of the brain in subjects with Regressive Autism. In addition, there was no significant difference in PKA activity or expression of PKA (C-a) between non-Regressive Autism and control groups. These results suggest that regression in Autism may be associated, i
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PKA activity in different brain regions from Regressive Autism, non-Regressive Autism, and age-matched control subjects.
2013Co-Authors: Ved Chauhan, Michael J. Flory, Abha ChauhanAbstract:The Autism group comprises combined Regressive and non-Regressive Autism sub-groups. Brain homogenates were prepared, and activity of PKA was measured as described in Materials and Methods. Data represent mean ± S.E.
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Relative protein levels of PKA (C-α) in the frontal cortex of Regressive Autism, non-Regressive Autism, and age-matched control subjects.
2013Co-Authors: Ved Chauhan, Michael J. Flory, Abha ChauhanAbstract:Western blot analyses of C-α subunit of PKA in the frontal cortex of individuals with Regressive and non-Regressive Autism, and age-matched control subjects are represented in Fig. 2A. The relative density of PKA (C-α) normalized with the density of β-actin (loading control) is shown in Fig. 2B. Data represent mean ± S.E.
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Reduced activity of protein kinase C in the frontal cortex of subjects with Regressive Autism: relationship with developmental abnormalities.
International journal of biological sciences, 2012Co-Authors: Abha Chauhan, Ved ChauhanAbstract:Autism is a neurodevelopmental disorder with unknown etiology. In some cases, typically developing children regress into clinical symptoms of Autism, a condition known as Regressive Autism. Protein kinases are essential for G-protein-coupled receptor-mediated signal transduction, and are involved in neuronal functions, gene expression, memory, and cell differentiation. Recently, we reported decreased activity of protein kinase A (PKA) in the frontal cortex of subjects with Regressive Autism. In the present study, we analyzed the activity of protein kinase C (PKC) in the cerebellum and different regions of cerebral cortex from subjects with Regressive Autism, autistic subjects without clinical history of regression, and age-matched control subjects. In the frontal cortex of subjects with Regressive Autism, PKC activity was significantly decreased by 57.1% as compared to age-matched control subjects (p = 0.0085), and by 65.8% as compared to non-regressed autistic subjects (p = 0.0048). PKC activity was unaffected in the temporal, parietal and occipital cortices, and in the cerebellum in both Autism groups, i.e., Regressive and non-regressed Autism as compared to control subjects. These results suggest brain region-specific alteration of PKC activity in the frontal cortex of subjects with Regressive Autism. Further studies showed a negative correlation between PKC activity and restrictive, repetitive and stereotyped pattern of behavior (r= -0.084, p = 0.0363) in autistic individuals, suggesting involvement of PKC in behavioral abnormalities in Autism. These findings suggest that regression in Autism may be attributed, in part, to alterations in G-protein-coupled receptor-mediated signal transduction involving PKA and PKC in the frontal cortex.
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Brain Region–Specific Decrease in the Activity and Expression of Protein Kinase A in the Frontal Cortex of Regressive Autism
PloS one, 2011Co-Authors: Ved Chauhan, Michael Flory, Abha ChauhanAbstract:Autism is a severe neurodevelopmental disorder that is characterized by impaired language, communication, and social skills. In Regressive Autism, affected children first show signs of normal social and language development but eventually lose these skills and develop autistic behavior. Protein kinases are essential in G-protein-coupled, receptor-mediated signal transduction and are involved in neuronal functions, gene expression, memory, and cell differentiation. We studied the activity and expression of protein kinase A (PKA), a cyclic AMP–dependent protein kinase, in postmortem brain tissue samples from the frontal, temporal, parietal, and occipital cortices, and the cerebellum of individuals with Regressive Autism; autistic subjects without a clinical history of regression; and age-matched developmentally normal control subjects. The activity of PKA and the expression of PKA (C-α), a catalytic subunit of PKA, were significantly decreased in the frontal cortex of individuals with Regressive Autism compared to control subjects and individuals with non-Regressive Autism. Such changes were not observed in the cerebellum, or the cortices from the temporal, parietal, and occipital regions of the brain in subjects with Regressive Autism. In addition, there was no significant difference in PKA activity or expression of PKA (C-α) between non-Regressive Autism and control groups. These results suggest that regression in Autism may be associated, in part, with decreased PKA-mediated phosphorylation of proteins and abnormalities in cellular signaling.
Ved Chauhan - One of the best experts on this subject based on the ideXlab platform.
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Brain region-specific decrease in the activity and expression of protein kinase A in the frontal cortex of Regressive Autism. PLoS One 2011; 6: e23751
2013Co-Authors: Ved Chauhan, Michael J. Flory, Abha ChauhanAbstract:Autism is a severe neurodevelopmental disorder that is characterized by impaired language, communication, and social skills. In Regressive Autism, affected children first show signs of normal social and language development but eventually lose these skills and develop autistic behavior. Protein kinases are essential in G-protein-coupled, receptor-mediated signal transduction and are involved in neuronal functions, gene expression, memory, and cell differentiation. We studied the activity and expression of protein kinase A (PKA), a cyclic AMP–dependent protein kinase, in postmortem brain tissue samples from the frontal, temporal, parietal, and occipital cortices, and the cerebellum of individuals with Regressive Autism; autistic subjects without a clinical history of regression; and age-matched developmentally normal control subjects. The activity of PKA and the expression of PKA (C-a), a catalytic subunit of PKA, were significantly decreased in the frontal cortex of individuals with Regressive Autism compared to control subjects and individuals with non-Regressive Autism. Such changes were not observed in the cerebellum, or the cortices from the temporal, parietal, and occipital regions of the brain in subjects with Regressive Autism. In addition, there was no significant difference in PKA activity or expression of PKA (C-a) between non-Regressive Autism and control groups. These results suggest that regression in Autism may be associated, i
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PKA activity in different brain regions from Regressive Autism, non-Regressive Autism, and age-matched control subjects.
2013Co-Authors: Ved Chauhan, Michael J. Flory, Abha ChauhanAbstract:The Autism group comprises combined Regressive and non-Regressive Autism sub-groups. Brain homogenates were prepared, and activity of PKA was measured as described in Materials and Methods. Data represent mean ± S.E.
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Relative protein levels of PKA (C-α) in the frontal cortex of Regressive Autism, non-Regressive Autism, and age-matched control subjects.
2013Co-Authors: Ved Chauhan, Michael J. Flory, Abha ChauhanAbstract:Western blot analyses of C-α subunit of PKA in the frontal cortex of individuals with Regressive and non-Regressive Autism, and age-matched control subjects are represented in Fig. 2A. The relative density of PKA (C-α) normalized with the density of β-actin (loading control) is shown in Fig. 2B. Data represent mean ± S.E.
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Reduced activity of protein kinase C in the frontal cortex of subjects with Regressive Autism: relationship with developmental abnormalities.
International journal of biological sciences, 2012Co-Authors: Abha Chauhan, Ved ChauhanAbstract:Autism is a neurodevelopmental disorder with unknown etiology. In some cases, typically developing children regress into clinical symptoms of Autism, a condition known as Regressive Autism. Protein kinases are essential for G-protein-coupled receptor-mediated signal transduction, and are involved in neuronal functions, gene expression, memory, and cell differentiation. Recently, we reported decreased activity of protein kinase A (PKA) in the frontal cortex of subjects with Regressive Autism. In the present study, we analyzed the activity of protein kinase C (PKC) in the cerebellum and different regions of cerebral cortex from subjects with Regressive Autism, autistic subjects without clinical history of regression, and age-matched control subjects. In the frontal cortex of subjects with Regressive Autism, PKC activity was significantly decreased by 57.1% as compared to age-matched control subjects (p = 0.0085), and by 65.8% as compared to non-regressed autistic subjects (p = 0.0048). PKC activity was unaffected in the temporal, parietal and occipital cortices, and in the cerebellum in both Autism groups, i.e., Regressive and non-regressed Autism as compared to control subjects. These results suggest brain region-specific alteration of PKC activity in the frontal cortex of subjects with Regressive Autism. Further studies showed a negative correlation between PKC activity and restrictive, repetitive and stereotyped pattern of behavior (r= -0.084, p = 0.0363) in autistic individuals, suggesting involvement of PKC in behavioral abnormalities in Autism. These findings suggest that regression in Autism may be attributed, in part, to alterations in G-protein-coupled receptor-mediated signal transduction involving PKA and PKC in the frontal cortex.
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Brain Region–Specific Decrease in the Activity and Expression of Protein Kinase A in the Frontal Cortex of Regressive Autism
PloS one, 2011Co-Authors: Ved Chauhan, Michael Flory, Abha ChauhanAbstract:Autism is a severe neurodevelopmental disorder that is characterized by impaired language, communication, and social skills. In Regressive Autism, affected children first show signs of normal social and language development but eventually lose these skills and develop autistic behavior. Protein kinases are essential in G-protein-coupled, receptor-mediated signal transduction and are involved in neuronal functions, gene expression, memory, and cell differentiation. We studied the activity and expression of protein kinase A (PKA), a cyclic AMP–dependent protein kinase, in postmortem brain tissue samples from the frontal, temporal, parietal, and occipital cortices, and the cerebellum of individuals with Regressive Autism; autistic subjects without a clinical history of regression; and age-matched developmentally normal control subjects. The activity of PKA and the expression of PKA (C-α), a catalytic subunit of PKA, were significantly decreased in the frontal cortex of individuals with Regressive Autism compared to control subjects and individuals with non-Regressive Autism. Such changes were not observed in the cerebellum, or the cortices from the temporal, parietal, and occipital regions of the brain in subjects with Regressive Autism. In addition, there was no significant difference in PKA activity or expression of PKA (C-α) between non-Regressive Autism and control groups. These results suggest that regression in Autism may be associated, in part, with decreased PKA-mediated phosphorylation of proteins and abnormalities in cellular signaling.
Frank Destefano - One of the best experts on this subject based on the ideXlab platform.
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MMR vaccination and Autism: is there a link?
Expert opinion on drug safety, 2002Co-Authors: Frank Destefano, William W. ThompsonAbstract:In 1998, a report was published describing 12 patients with inflammatory bowel conditions and Regressive developmental disorders consisting primarily of Autism. The authors hypothesised that MMR vaccine may have been responsible for the bowel dysfunction which subsequently resulted in the neurodevelopmental disorders. The suggestion that measles vaccine may cause Autism through a persistent bowel infection generated much interest since it provided a possible biological mechanism for a causal association. Epidemiological studies, however, have not found an association between MMR vaccination and Autism. Autism has a strong genetic component and its associated neurological defects probably occur during embryonic development. It seems unlikely that a vaccination that is given after birth could cause Autism. In a minority of cases, Autism may have onset after 1 year of age (Regressive Autism) but the one epidemiological study that included such cases did not find an association with MMR vaccination. Currently...
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Autism and Measles-Mumps-Rubella Vaccination
CNS Drugs, 2001Co-Authors: Frank Destefano, Robert T. ChenAbstract:It has been suggested that vaccination, particularly with measles-mumps-rubella (MMR) vaccine, may be related to the development of Autism. The main evidence for a possible association is that the prevalence of Autism has been increasing at the same time that infant vaccination coverage has increased, and that in some cases there is an apparent temporal association in which autistic characteristics are first noted shortly after vaccination. Although the prevalence of Autism and similar disorders appears to have increased recently, it is not clear if this is an actual increase or the result of increased recognition and changes in diagnostic criteria. The apparent onset of Autism in close proximity to vaccination may be a coincidental temporal association. The clinical evidence in support of an association derives from a series of 12 patients with inflammatory bowel conditions and Regressive developmental disorders, mostly Autism. The possibility that measles vaccine may cause Autism through a persistent bowel infection has generated much interest, since it provides a possible biological mechanism. Epidemiological studies, however, have not found an association between MMR vaccination and Autism. The epidemiological findings are consistent with current understanding of the pathogenesis of Autism, which has a strong genetic component and in which the neurological defects probably occur early in embryonic development. It seems unlikely that a vaccination that is given after birth could cause Autism. A minority of cases of Autism may have onset after 1 year of age (Regressive Autism), but the single epidemiological study that included such cases did not find an association with MMR vaccination. Currently, the weight of the available epidemiological and related evidence does not support a causal association between MMR vaccine, or any other vaccine or vaccine constituent, and Autism.
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More evidence to reassure physicians and parents about vaccination.
The Western journal of medicine, 2001Co-Authors: Frank DestefanoAbstract:It has been suggested that vaccination, particularly with the mumps, measles, and rubella (MMR) vaccine, may be related to the development of Autism. One of the arguments for a possible association is that the prevalence of Autism has been increasing at the same time that infant vaccination coverage has increased. Although the prevalence of Autism and similar disorders appears to have increased recently, whether this is an actual increase or due to increased recognition and changes in diagnostic criteria is not clear. The clinical evidence in support of an association derives from a report of 12 patients with inflammatory bowel conditions and Regressive developmental disorders, mostly Autism.1 The authors' speculation that MMR vaccine may cause Autism through a persistent bowel infection has generated much interest because it provides a possible biologic mechanism for a causal association. A subsequent epidemiologic study in the United Kingdom, however, did not find an association between MMR vaccination and the onset of Autism.2 Several different analyses were performed, all of which showed no association. One of the findings of the study was that although Autism prevalence had increased in the study population, the increase started before the introduction of routine MMR vaccination in Britain in 1987, and there was not an abrupt increase in prevalence after the vaccine's introduction. The interpretation of this finding, however, has been debated. The study by Kaye et al provides evidence that the Autism trends in the United Kingdom are not related to MMR vaccination. The study was a time trend analysis of a large database of general medical practices in the United Kingdom and compared diagnoses of Autism with coverage of MMR vaccine. There was a striking 7-fold increase in the incidence of newly diagnosed cases of Autism from 1988 to 1999. Among boys, the incidence of Autism increased 4-fold for those born in the years from 1988 to 1993. For the same birth cohorts, the coverage of MMR vaccine was stable at more than 95%. Thus, there was no correlation between the large increase in Autism diagnoses and MMR coverage. Studies in Sweden and California have also not found any temporal correlations between MMR coverage and Autism trends.3,4 The epidemiologic findings are consistent with current understanding of the pathogenesis of Autism, which has a strong genetic component and whose neurologic defects probably occur early in embryonic development. It seems unlikely that a vaccine that is given after birth could cause Autism. A few cases of Autism may have onset after 1 year of age (Regressive Autism), but the 1 epidemiologic study that included such cases did not find an association with MMR vaccination.2 Currently, the weight of the available epidemiologic and related evidence does not support a causal association between MMR vaccine—or any other vaccine or vaccine constituent—and Autism. The possibility of an idiosyncratic reaction in certain susceptible persons cannot be ruled out, but such occurrences would have to be rare and have not been detectable in large epidemiologic studies. In general, parents and physicians should be reassured that MMR vaccine does not cause Autism.
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Autism and Measles-Mumps-Rubella Vaccination: Controversy Laid to Rest?
CNS drugs, 2001Co-Authors: Frank Destefano, Robert ChenAbstract:It has been suggested that vaccination, particularly with measles-mumps-rubella (MMR) vaccine, may be related to the development of Autism. The main evidence for a possible association is that the prevalence of Autism has been increasing at the same time that infant vaccination coverage has increased, and that in some cases there is an apparent temporal association in which autistic characteristics are first noted shortly after vaccination. Although the prevalence of Autism and similar disorders appears to have increased recently, it is not clear if this is an actual increase or the result of increased recognition and changes in diagnostic criteria. The apparent onset of Autism in close proximity to vaccination may be a coincidental temporal association. The clinical evidence in support of an association derives from a series of 12 patients with inflammatory bowel conditions and Regressive developmental disorders, mostly Autism. The possibility that measles vaccine may cause Autism through a persistent bowel infection has generated much interest, since it provides a possible biological mechanism. Epidemiological studies, however, have not found an association between MMR vaccination and Autism. The epidemiological findings are consistent with current understanding of the pathogenesis of Autism, which has a strong genetic component and in which the neurological defects probably occur early in embryonic development. It seems unlikely that a vaccination that is given after birth could cause Autism. A minority of cases of Autism may have onset after 1 year of age (Regressive Autism), but the single epidemiological study that included such cases did not find an association with MMR vaccination. Currently, the weight of the available epidemiological and related evidence does not support a causal association between MMR vaccine, or any other vaccine or vaccine constituent, and Autism.
Paul Ashwood - One of the best experts on this subject based on the ideXlab platform.
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Peripheral Blood Leukocyte Production of BDNF following Mitogen Stimulation in Early Onset and Regressive Autism
American journal of biochemistry & biotechnology, 2008Co-Authors: Amanda M. Enstrom, Robin L Hansen, Irva Hertz-picciotto, Lisa A. Croen, Judith A Van De Water, Charity Onore, Angela Tarver, Paul AshwoodAbstract:Brain-derived neurotrophic factor (BDNF) is critical for neuronal differentiation and synaptic development. BDNF is also implicated in the development of psychological disorders including depression, bipolar disorder and schizophrenia. Previously, elevated BDNF levels were observed in neonatal blood samples from infants who were later diagnosed with Autism when compared with children who developed normally, suggesting that BDNF may be involved in the development of Autism. BDNF is produced by activated brain microglial cells, a cellular phenotype that shares several features with peripheral macrophages, suggesting an important role for the immune system in BDNF production. We hypothesized that under mitogenic stimulation, peripheral blood mononuclear cells obtained from children with Autism may have altered BDNF production compared with age-matched typically developing control subjects. In addition, we examined the differences between the production of BDNF in classic/early-onset Autism and children who had a Regressive form of Autism. We show here that plasma levels of BDNF levels are increased in children with Autism, especially in early onset Autism subjects. Furthermore, under mitogenic stimulation with PHA and LPS, BDNF production is significantly increased in children with Autism compared with typically developing subjects. However, stimulation with tetanus toxoid results in a decreased response in children with Autism. This data suggest that immune cell-derived production of BDNF could be an important source for the increased BDNF that is detected in some subjects with Autism. As a neurotrophic factor produced by immune cells, BDNF could help elucidate the role of the immune system in neurodevelopment and neuronal maintenance, which may be dysregulated in Autism.
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Autism: maternally derived antibodies specific for fetal brain proteins.
Neurotoxicology, 2007Co-Authors: Daniel Braunschweig, Paul Ashwood, Robin L Hansen, Irva Hertz-picciotto, Lisa A. Croen, Paula Krakowiak, Isaac N. Pessah, Judith A Van De WaterAbstract:Autism is a profound disorder of neurodevelopment with poorly understood biological origins. A potential role for maternal autoantibodies in the etiology of some cases of Autism has been proposed in previous studies To investigate this hypothesis, maternal plasma antibodies against human fetal and adult brain proteins were analyzed by western blot in 61 mothers of children with autistic disorder and 102 controls matched for maternal age and birth year (62 mothers of typically developing children (TD) and 40 mothers of children with non-ASD developmental delays (DD)). We observed reactivity to two protein bands at approximately 73kDa and 37kDa in plasma from 7 of 61 (11.5%) mothers of children with Autism (AU) against fetal but not adult brain, which was not noted in either control group (TD; 0/62 p=0.0061 and DD; 0/40 p=0.0401). Further, the presence of reactivity to these two bands correlated with a diagnosis of behavioral regression in the child when compared to the TD (p=0.0019) and DD (0.0089) groups. Individual reactivity to the 37kDa band was observed significantly more often in the AU population compared with TD (p=0.0086) and DD (p=0.002) mothers, yielding a 5.69-fold odds ratio (95% confidence interval 2.09 - 15.51) associated with this band. The presence of these antibodies in the plasma of some mothers of children with Autism, as well as the differential findings between mothers of children with early onset and Regressive Autism may suggest an association between the transfer of IgG autoantibodies during early neurodevelopment and the risk of developing of Autism in some children.
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Brief report: plasma leptin levels are elevated in Autism: association with early onset phenotype?
Journal of autism and developmental disorders, 2007Co-Authors: Paul Ashwood, Christina Kwong, Robin L Hansen, Irva Hertz-picciotto, Lisa A. Croen, Paula Krakowiak, Wynn Walker, Isaac N. Pessah, Judith A Van De WaterAbstract:There is evidence of both immune dysregulation and autoimmune phenomena in children with Autism spectrum disorders (ASD). We examined the hormone/cytokine leptin in 70 children diagnosed with Autism (including 37 with regression) compared with 99 age-matched controls including 50 typically developing (TD) controls, 26 siblings without Autism, and 23 children with developmental disabilities (DD). Children with Autism had significantly higher plasma leptin levels compared with TD controls (p < .006). When further sub-classified into regression or early onset Autism, children with early onset Autism had significantly higher plasma leptin levels compared with children with Regressive Autism (p < .042), TD controls (p < .0015), and DD controls (p < .004). We demonstrated an increase in leptin levels in Autism, a finding driven by the early onset group.
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Focal-enhanced gastritis in Regressive Autism with features distinct from Crohn's and Helicobacter pylori gastritis.
The American journal of gastroenterology, 2004Co-Authors: Franco Torrente, Andrew Anthony, Robert B. Heuschkel, Michael A. Thomson, Paul Ashwood, F.r.c.p. Simon H. MurchAbstract:Focal-Enhanced Gastritis in Regressive Autism with Features Distinct from Crohn's and Helicobacter Pylori Gastritis
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intestinal lymphocyte populations in children with Regressive Autism evidence for extensive mucosal immunopathology
Journal of Clinical Immunology, 2003Co-Authors: Paul Ashwood, Franco Torrente, Andrew Anthony, Alicia A Pellicer, J A Walkersmith, Aj WakefieldAbstract:Inflammatory intestinal pathology has been reported in children with Regressive Autism (affected children). Detailed analysis of intestinal biopsies in these children indicates a novel lymphocytic enterocolitis with autoimmune features; however, links with cognitive function remain unclear. To characterize further, the nature and extent of this disease we examined the mucosal infiltrate using flow cytometry. Duodenal, ileal, and colonic biopsies were obtained from 52 affected children, 25 histologically normal, and 54 histologically inflamed, developmentally normal controls. Epithelial and lamina propria lymphocyte populations were isolated and examined by multicolor flow cytometry. Adjacent biopsies were assessed by semiquantitative histopathology. At all sites, CD3(+) and CD3(+)CD8(+) IEL as well as CD3(+) LPL were significantly increased in affected children compared with developmentally normal noninflamed control groups (p<0.01) reaching levels similar to inflamed controls. In addition, two populations--CD3(+)CD4(+) IEL and LP CD19(+) B cells--were significantly increased in affected children compared with both noninflamed and inflamed control groups including IBD, at all sites examined (p<0.01). Histologically there was a prominent mucosal eosinophil infiltrate in affected children that was significantly lower in those on a gluten- and casein-free diet, although lymphocyte populations were not influenced by diet. The data provide further evidence of a pan-enteric mucosal immunopathology in children with Regressive Autism that is apparently distinct from other inflammatory bowel diseases.
Michael Flory - One of the best experts on this subject based on the ideXlab platform.
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Brain Region–Specific Decrease in the Activity and Expression of Protein Kinase A in the Frontal Cortex of Regressive Autism
PloS one, 2011Co-Authors: Ved Chauhan, Michael Flory, Abha ChauhanAbstract:Autism is a severe neurodevelopmental disorder that is characterized by impaired language, communication, and social skills. In Regressive Autism, affected children first show signs of normal social and language development but eventually lose these skills and develop autistic behavior. Protein kinases are essential in G-protein-coupled, receptor-mediated signal transduction and are involved in neuronal functions, gene expression, memory, and cell differentiation. We studied the activity and expression of protein kinase A (PKA), a cyclic AMP–dependent protein kinase, in postmortem brain tissue samples from the frontal, temporal, parietal, and occipital cortices, and the cerebellum of individuals with Regressive Autism; autistic subjects without a clinical history of regression; and age-matched developmentally normal control subjects. The activity of PKA and the expression of PKA (C-α), a catalytic subunit of PKA, were significantly decreased in the frontal cortex of individuals with Regressive Autism compared to control subjects and individuals with non-Regressive Autism. Such changes were not observed in the cerebellum, or the cortices from the temporal, parietal, and occipital regions of the brain in subjects with Regressive Autism. In addition, there was no significant difference in PKA activity or expression of PKA (C-α) between non-Regressive Autism and control groups. These results suggest that regression in Autism may be associated, in part, with decreased PKA-mediated phosphorylation of proteins and abnormalities in cellular signaling.
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brain region specific decrease in the activity and expression of protein kinase a in the frontal cortex of Regressive Autism
PLOS ONE, 2011Co-Authors: Ved Chauhan, Michael Flory, Abha ChauhanAbstract:Autism is a severe neurodevelopmental disorder that is characterized by impaired language, communication, and social skills. In Regressive Autism, affected children first show signs of normal social and language development but eventually lose these skills and develop autistic behavior. Protein kinases are essential in G-protein-coupled, receptor-mediated signal transduction and are involved in neuronal functions, gene expression, memory, and cell differentiation. We studied the activity and expression of protein kinase A (PKA), a cyclic AMP–dependent protein kinase, in postmortem brain tissue samples from the frontal, temporal, parietal, and occipital cortices, and the cerebellum of individuals with Regressive Autism; autistic subjects without a clinical history of regression; and age-matched developmentally normal control subjects. The activity of PKA and the expression of PKA (C-α), a catalytic subunit of PKA, were significantly decreased in the frontal cortex of individuals with Regressive Autism compared to control subjects and individuals with non-Regressive Autism. Such changes were not observed in the cerebellum, or the cortices from the temporal, parietal, and occipital regions of the brain in subjects with Regressive Autism. In addition, there was no significant difference in PKA activity or expression of PKA (C-α) between non-Regressive Autism and control groups. These results suggest that regression in Autism may be associated, in part, with decreased PKA-mediated phosphorylation of proteins and abnormalities in cellular signaling.