Biomedical subjects

Christopher R Loiselle

Publications and source records attributed to Christopher R Loiselle.

6 recordsLinked to original sources

PubMed2005

Microinfusion of antineuronal antibodies into rodent striatum: failure to differentiate between elevated and low titers.

An autoimmune-mediated mechanism has been proposed for several pediatric movement disorders. In a three-center (Brown, Yale, and Johns Hopkins) collaborative effort, serum antineuronal antibodies (ANAb) were measured by use of ELISA or immunohistochemical techniques on 35 children (mean age 11.4 years) with Tourette syndrome, attention deficit hyperactivity disorder, and/or obsessive compulsive disorder. Eight sera, 4 containing the highest and 4 the lowest levels of ANAb, were identified at each institution. Selected sera (total of 9 with elevated and 7 with low ANAb) were re-encoded and sent to each center for infusion into the ventrolateral striatum of 16 male Sprague-Dawley rats. Animals were observed for behavioral abnormalities for 3 days before the start of infusion, during infusion on days 2-4, and for 2 days after infusion. Combined stereotypy scores increased after antibody infusion, but there was no significant effect based on serum titer (p=0.85). Scores differed among centers, but analyses based on individual institutional data again failed to show an effect based on elevated or low ANAb values (Brown, p=0.95; Yale and Johns Hopkins, p=0.81). Post hoc studies with sham surgery and infusion of phosphate-buffered saline support suggestions of nonspecific behavioral effects unrelated to antibody titer. This report emphasizes that any conclusions about antibody-mediated movement disorders that are based upon results from the rodent infusion model must be considered with caution.

Adolescent↗

PubMed2004

Microarray analysis in Tourette syndrome postmortem putamen.

Gene expression patterns in the postmortem putamen of patients with Tourette syndrome (TS) were investigated using cDNA microarrays. A cDNA neuroarray comprising 1537 genes known to be related to neurological or neuropsychiatric disorders was used to compare patient samples (n=3) with those from control subjects (n=4). Z test and Z ratio were used to analyze results; seven genes were found to be upregulated according to our definition (P<0.1, two-tailed, for Z test; P<0.05 for Z ratio) and three were found to be downregulated. Validation experiments were performed using reverse transcription polymerase chain reaction (RT-PCR) and semiquantitative Western blot analyses. RT-PCR showed concordance with microarray in seven of nine selected genes. In contrast, Western blot analyses performed with five proteins showed that only two of five had similar trends between protein content and level of gene expression. The authors note the inherent difficulty in applying microarray technology to complex neurological disorders such as the TS and conclude that further investigations are required to understand how altered expression of these genes is related to the pathophysiology of the disorder.

Adult↗

PubMed2004

Striatal microinfusion of Tourette syndrome and PANDAS sera: failure to induce behavioral changes.

Rodent striatal microinfusions have been suggested as a model for assessing the behavioral effects induced by antineuronal antibodies. We used this approach to evaluate the proposed autoimmune etiology for Tourette syndrome (TS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). Sera were assessed from patients with TS (n = 9) preselected based on the presence of elevated enzyme-linked immunosorbent assay optical densities against putamen homogenate and sera from patients with PANDAS (n = 8), selected from a larger group assayed for antibodies against a putamen synaptosomal preparation. The effect of antibodies against the streptococcal M5 protein were also studied. A total of 44 Fischer rats received bilateral infusion of sera: 23 ventral striatum (5 PANDAS, 5 TS, 5 anti-M5 protein, and 8 control); 21 ventrolateral striatum (5 PANDAS, 5 TS, 5 anti-M5 protein, and 6 controls). Cannulas were placed bilaterally and symmetrically by stereotactic techniques. After animals were allowed to recover for 1 week, sera were microinfused for 3 days. Animal behavior was then simultaneously quantified by daily observation and monitoring using automated activity boxes for 10 days after infusion. No significant alterations in stereotypic behavior or movement were observed between the PANDAS, TS, or anti-M5 protein and control groups. Our findings are in contrast to previous reports, and suggest the need for further investigations to determine the validity of the model and of autoimmune-mediated hypotheses for pediatric movement disorders.

Animals↗

PubMed2004

Anti-basal ganglia antibodies in PANDAS.

An autoimmune-mediated mechanism involving molecular mimicry has been proposed for a variety of pediatric movement disorders that occur after a streptococcal infection. In this study, anti-basal ganglia antibodies (ABGA) were measured in 15 children with the diagnosis of pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS) and compared with those in 15 controls. ELISA and Western immunoblotting (WB) methods were used to detect ABGA against supernatant (S1), pellet (P2), and synaptosomal preparations from adult postmortem caudate, putamen, and globus pallidus. ELISA optical density values did not differ between PANDAS patients and controls across all preparations. Immunoblotting identified multiple bands in all subjects with no differences in the number of bands or their total density. Discriminant analysis, used to assess mean binding patterns, showed that PANDAS patients differed from controls only for the caudate S1 fraction (Wilks' lambda = 0.0236, P < 0.0002), with PANDAS-primarily tic subjects providing the greatest discrimination. Among the epitopes contributing to differences between PANDAS and control in the caudate S1 fraction, mean binding to the epitope at 183 kDa was the most different between groups. In conclusion, ELISA measurements do not differentiate between PANDAS and controls, suggesting a lack of major antibody changes in this disorder. Further immunoblot analyses using a caudate supernatant fraction are required to completely exclude the possibility of minor antibody repertoire differences in PANDAS subjects, especially in those who primarily have tics.

Adolescent↗

PubMed2003

Anti-basal ganglia antibody abnormalities in Sydenham chorea.

Anti-basal ganglia antibodies (ABGA) were measured in nine children with Sydenham chorea (SC) and compared to nine controls. Enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) methods were used to detect ABGA against supernatant (S1), pellet, and synaptosomal preparations from adult and pediatric postmortem caudate, putamen, and globus pallidus. ELISA optical density (OD) values were higher in SC patients than controls across all preparations, but did not reach a level of significance. Although WB identified multiple bands in all subjects, discriminant analysis showed that the mean binding patterns of SC patients were significantly different from control, most notably in the caudate S1 fraction (Wilks' lambda=0.011, p<0.0001). Numerous antigens contributed to differences between groups; the two most defining molecular masses were at 126 and 113 kDa. In contrast to WB with discriminant analysis, ELISA measurements did not significantly differentiate between the SC group and controls.

Adolescent↗

PubMed2003

Antistreptococcal, neuronal, and nuclear antibodies in Tourette syndrome.

Previous studies have suggested associations between Tourette syndrome and attention-deficit-hyperactivity disorder and antistreptococcal antibodies and between Tourette syndrome and antinuclear antibodies. In this study, antistreptolysin O, antideoxyribonuclease B, antinuclear, and antineuronal antibodies were measured in 41 children with Tourette syndrome and 38 controls, selected without regard to history of streptococcal infection. Results revealed that mean antistreptococcal titers did not differ between diagnostic groups. In addition, multiple regression analysis was unable to predict antistreptococcal antibody titers according to age and diagnosis. The frequency of elevated antistreptolysin O titers, based on a cutoff of 1:240, was significantly higher (P = 0.04) in patients with attention-deficit-hyperactivity disorder (64%) than in the group without attention-deficit-hyperactivity disorder (34%) but not when dichotomized according to age-matched normal values. No analysis of antideoxyribonuclease B titers identified any differences between groups. Antinuclear antibody titers were at least 1:160 in three of 33 Tourette syndrome patients; only one subject manifested a homogeneous staining pattern. Multiple regression analyses were unable to predict antinuclear, antineuronal, or anti-HTB-10 antibody titers according to the combination of age, diagnosis, and antistreptococcal titer. We suggest that longitudinal rather than single-point-in-time laboratory measurements be evaluated before definitive conclusions are drawn on associations between the diagnosis of Tourette syndrome, attention-deficit-hyperactivity disorder, or obsessive-compulsive disorders and antistreptococcal or antinuclear antibody titers.

Adolescent↗