Elevated serum neurotensin and CRH levels in children with autistic spectrum disorders and tail-chasing Bull Terriers with a phenotype similar to autism
I Tsilioni1, N Dodman2, A I Petra1, A Taliou3, K Francis3, A Moon-Fanelli2, L Shuster1 and T C Theoharides1,4,5
1Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA, USA
2Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, Grafton, MA, USA
3Second Department of Psychiatry, Attikon General Hospital, Athens University, Athens, Greece
4Department of Internal Medicine, Tufts University School of Medicine and Tufts Medical Center, Boston, MA, USA
5Department of Psychiatry, Tufts University School of Medicine and Tufts Medical Center, Boston, MA, USA
Correspondence: Professor TC Theoharides, Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, 136 Harrison Avenue, Suite J304, Boston, MA 02111, USA. E-mail: firstname.lastname@example.org
Received 1 May 2014; Revised 10 July 2014; Accepted 12 August 2014
Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by defects in communication and social interactions, as well as stereotypic behaviors. Symptoms typically worsen with anxiety and stress. ASD occur in early childhood, often present with regression and have a prevalence of 1 out of 68 children. The lack of distinct pathogenesis or any objective biomarkers or reliable animal models hampers our understanding and treatment of ASD. Neurotensin (NT) and corticotropin-releasing hormone (CRH) are secreted under stress in various tissues, and have proinflammatory actions. We had previously shown that NT augments the ability of CRH to increase mast cell (MC)-dependent skin vascular permeability in rodents. CRH also induced NT receptor gene and protein expression in MCs, which have been implicated in ASD. Here we report that serum of ASD children (4–10 years old) has significantly higher NT and CRH levels as compared with normotypic controls. Moreover, there is a statistically significant correlation between the number of children with gastrointestinal symptoms and high serum NT levels. In Bull Terriers that exhibit a behavioral phenotype similar to the clinical presentation of ASD, NT and CRH levels are also significantly elevated, as compared with unaffected dogs of the same breed. Further investigation of serum NT and CRH, as well as characterization of this putative canine breed could provide useful insights into the pathogenesis, diagnosis and treatment of ASD.
What is Neurotensin?
From Quest Diagnostic website
Neurotensin is a 13-amino acid peptide, produced primarily by endocrine cells of the ileal mucosa. Physiological actions of Neurotensin include hypertension, vasodilation, hyperglycemia, and inhibition of gastric motility. Its C-terminus is similar to Angiotensin I. It is a potent analgesic affecting hypothermia, muscle relaxation, and decreased motor activity. Pancreatic Polypeptide secretion is strongly stimulated by Neurotensin. Neurotensin appears to cause the release of Luteinizing Hormone-Releasing Hormone and Corticotropin Releasing Hormone, effecting the release of Luteinizing Hormone, Follicle Stimulatng Hormone, and ACTH, but not Thyroid Stimulatng Hormone or Growth Hormone. Neurotensin also stimulates pancreatic bicarbonate and intestinal secretion. Neurotensin levels are stimulated by food and Bombesin. Elevated levels have been found in pancreatic endocrine tumors, oat cell, squamous, and adenocarcinomas. Elevated levels have been found to cause watery diarrhea.