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A Low Brain Serotonergic Neurotransmission in Children With Type 1 Diabetes Detected Through the Intensity Dependence of Auditory-Evoked Potentials

¹ Laboratory of Developmental Neurochemistry, Specialties Hospital, XXI Century, National Medical Center, Mexican Institute of Social Security, Mexico City, Mexico
² Service of Endocrinology, Pediatric Hospital, XXI Century, National Medical Center, Mexican Institute of Social Security, Mexico City, Mexico
³ Laboratory of Neurontogeny, Department of Physiology, Biophysics and Neurosciences, Center of Research and Advanced Studies, National Polytechnic Institute, Mexico City, Mexico

Address correspondence and reprint requests to Gabriel Manjarrez, Laboratory of Developmental Neurochemistry, Specialties Hospital, XXI Century, National Medical Center, Mexican Institute of Social Security, Av. Cuauhtemoc 330, Col. Doctores, CP 06720, Mexico City, Mexico. E-mail: willisga{at}df1.telmex.net.mx

OBJECTIVE—To determine in children with type 1 diabetes the plasma free fraction of L-tryptophan (FFT) and the intensity-dependent auditory-evoked potentials (IDAEPs) as indicators of possible changes in brain serotonergic neurotransmission.

RESEARCH DESIGN AND METHODS—A prospective and comparative study was performed in children with type 1 diabetes and normal control subjects. We measured FFT, bound and total plasma L-tryptophan, neutral amino acids (NAAs), albumin, free fatty acids (FFAs), glucose, and HbA_1c(A1C) and recorded IDAEPs with four intensities (40, 60, 90, and 103 dB).

RESULTS—The glycemia, A1C, FFAs, and NAAs in plasma were significantly elevated. The FFT and the FFT-to-total L-tryptophan and FFT-to-NAA ratios were reduced. The latencies of N1 and P2 increased at all intensities and the slope of the amplitude/stimulus intensity function (ASF slope) of the N1/P2 component significantly increased.

CONCLUSIONS—The decrease of the FFT in plasma and increase in the N1/P2 component amplitude may reflect a functional relationship between the brain serotonergic activity with the N1/P2 changes. The increase of the ASF slope in children with type 1 diabetes suggests that the response of the auditory cortex to sound intensity stimulus may be regulated by the serotonergic tone and that decreased serotonergic neurotransmission may provoke a different behavior of sensory cortices. Therefore, the IDAEP (N1/P2 component) may be an electrophysiological indicator of brain changes of serotonergic neurotransmission in children with type 1 diabetes. These changes may be related to psychoemotional manifestations observed in diabetic children such as anxiety and depression.

Abbreviations: 5-HT, 5-ASF, amplitude/stimulus intensity function • BBB, blood-brain barrier • FFA, free fatty acid • FFT, free fraction of L-tryptophan • IDAEP, intensity-dependent auditory-evoked potential • NAA, neutral amino acid

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