International Meeting for Autism Research (London, May 15-17, 2008): Can serotonin brain changes in Down syndrome provide insights into the etiology of Autism?

Saturday, May 17, 2008

Champagne Terrace/Bordeaux (Novotel London West)

E. Azmitia , Biology, Psychiatry, New York University, New York, NY

Y. Rodriguez , Neuroscience, New York University, New York, NY

X. P. Hou , Biology, New York University, New York, NY

P. Whitaker-Azmitia , Psychology, State University of New York, Stony Brook, NY

J. Wegiel , Psychiatry, New York University, New York, NY

Background: Serum serotonin levels in children are increased in Autism but decreased in Down syndrome. Serotonin functions as a developmental trophic factor in the mammalian brain with high levels promoting accelerated maturation and low levels resulting in delayed maturation. The sizes of neurons in the brains of autism children are smaller, but the sizes in Down syndrome are larger.

Objectives: Following the serotonin axons in the postmortem brains of Down syndrome adults compared to undiagnosed controls may provide insights into how peripheral serotonin levels may impact the CNS serotonin system.

Methods: Brains from DS (28-61 yrs) and control (33-61 yrs) were obtained from IBR using the Hemispheric PEG protocol. The brains were fixed in 10% formalin for at least 30 days. Slabs through the temporal gyrus were dehydrated in ethyl alcohol and embedded with Polyethylene glycol. Serial 50-um-thick sections are cut and stored in 70% ethyl alcohol. Serotonin axons were visualized using an Anti 5-HT-transporter Rabbit Polyclonal Antibody.

Results: In control brains, 5-HTT-immunoreactive axons were seen in all brain regions examined. Highest levels occurred in hippocampus, entorhinal cortex and in layers III-IV of neocortex. Fibers were seen in fornix, white matter and perforant path. In the DS brains, an increased 5-HTT-IR expression was seen at all ages. The serotonin axons showed enlarged varicosities and clear evidence of pathology. Large dense aggregates began to form by age 28 and continued to increase in size with age. 5-HTT-IR aggregates formed pathological zones identified in surface plots. Neuronal sizes in layer III neurons showed increase in DS brains.

Conclusions: Lower serotonin serum levels are associated with larger neurons and increased serotonin aggregates in DS. Since serotonin serum levels are high in Autism, and neurons are smaller, we expect that serotonin innervation will be reduced in brains from autism patients. Funded by Autism Speaks

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