Disrupted brain thyroid hormone homeostasis and altered thyroid hormone-dependent brain gene expression in autism spectrum disorders.
The present study examined human postmortem brains for changes consistent with the hypothesis of local brain TH deficiency in autism spectrum disorders (ASD). Brain levels of oxidative stress marker - 3-nitrotyrosine (3-NT), iodothyronine deiodinase type 2(D2) and type 3 (D3), 3',3,5-triiodothyronine (T3) content, mercury content and gene expression levels were analyzed and compared in the several regions of postmortem brains derived from both male and female control and ASD cases, age 4-16 years. We report that some parameters measured, such as D2 are subject to rapid postmortem inactivation, while others that were analyzed showed both brain region- and sex-dependent changes. Levels of 3-NT were overall increased, T3 was decreased in the cortical regions of ASD brains, while mercury levels measured only in the extracortical regions were not different. The expression of several thyroid hormone (TH)-dependent genes was altered in ASD. Data reported here suggest the possibility of brain region-specific disruption of TH homeostasis and gene expression in autism.
Department of Psychiatry, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA. esulkowska@rics.bwh.harvard.edu; elzbieta_sajdel_ sulkowska@SGGW.pl.
A
A
Khan
J W
JW
Harney
A M
AM
Zavacki
E M
EM
Sajdel-Sulkowska
D000293:Adolescent; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics* / Q000378:metabolism*; D002675:Child, Preschool; D005260:Female; D015870:Gene Expression; D006706:Homeostasis; D006801:Humans; D007453:Iodide Peroxidase / Q000378:metabolism; D008297:Male; D008628:Mercury / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013963:Thyroid Hormones / Q000378:metabolism*; D014285:Triiodothyronine, Reverse / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D000097564:Iodothyronine Deiodinase Type II
D007453:Iodide Peroxidase; D008628:Mercury; D013963:Thyroid Hormones; D014285:Triiodothyronine, Reverse; D014443:Tyrosine; D000097564:Iodothyronine Deiodinase Type II; C002744:3-nitrotyrosine; C117274:iodothyronine deiodinase type III