A Functional Disturbance in the Auditory Cortex Related to a Low Serotonergic Neurotransmission in Women with Type 2 Diabetes

Abstract

Background/Aims: To determine if the slope of the amplitude/stimulus intensity function (ASF) of the N1/P2 component of the auditory evoked potential was increased in women with type 2 diabetes reflecting a low brain serotonergic activity in the auditory cortex. Methods: In a comparative study in women with type 2 diabetes and controls, we measured free, bound and total plasma L-tryptophan (L-Trp), neutral amino acids (NAA) and free fatty acids (FFA) and recorded the N1/P2 component of the auditory evoked potential. Results: The diabetic patients were overweight and FFA and NAA in plasma were significantly elevated. The free, bound to albumin and total L-Trp were decreased. The values of free/total L-Trp and free/NAA ratios were significantly lower. The latencies of N1 and P2 at all intensities and the slope ASF of the N1/P2 component significantly increased. Conclusion: The decrease of the free fraction of L-Trp in plasma and the increase of the ASF slope of the N1/P2 component reflect a functional relationship between the brain serotonergic activity and the N1/P2 changes in the auditory cortex, suggesting a cortical impaired activity associated with anomalies of brain serotonergic neurotransmission in women with type 2 diabetes. We proposed the ASF slope together with measurement of the plasma FFT as noninvasive clinical indicators of serotonergic neurotransmission in the brain in these as well as in other types of patients.

Functional change of the auditory cortex related to brain serotonergic neurotransmission in type 1 diabetic adolescents with and without depression

“…These tests were undertaken as noninvasive clinical indicators of brain serotonin biosynthesis and activity. The present results confirm that FFT and FFT/total L-Trp ratio are significantly decreased in only diabetic patients (Herrera et al 2003;Manjarrez et al 2006Manjarrez et al , 2007. Interestingly, diabetic subjects who were depressed showed a similar decrease of these biochemical markers.…”

“…These findings support a lowered activity of serotonergic neurotransmission in the brain during the diabetic state, particularly in the auditory cortex (Manjarrez et al 2006(Manjarrez et al , 2007, which may be detected through a change in the amplitude of the N1/P2 component of the intensity-dependent auditory-evoked potentials (IDAEPs) (Hegerl and Juckel 1993;Manjarrez et al 2001Manjarrez et al , 2005aManjarrez et al ,b, 2006Manjarrez et al , 2007. We also recently observed in patients with type 1 and 2 diabetes a significant increase in the slope of the amplitude/stimulus intensity function (ASF slope) of the N1/P2 component, obtained at various intensities of auditory stimuli (Manjarrez et al 2006(Manjarrez et al , 2007. More specifically, a strong increase in auditory-evoked cortical responses with increasing stimuli intensities does reflect a low serotonergic activity, whereas low-intensity dependence is assumed to result from high serotonergic function, as we have observed in infants and rats with intrauterine growth restriction (Manjarrez et al 2001(Manjarrez et al , 2005a.…”

“…In the diabetic state and during depression there is also an increase in catabolism of L-Trp due to stimulation of liver tryptophan oxygenase activity (Salder et al 1983). Diabetic patients also present an increase of neutral amino acids (NAA) that compete with L-Trp for its transport to the brain, decreasing even more its availability (Herrera et al 2003;Manjarrez et al 2006Manjarrez et al , 2007. This finding, together with an altered activity of tryptophan-5-hydroxylase, also supports a low serotonin biosynthesis (Herrera et al 2005).…”

“…Interestingly, diabetic patients without depression showed similar biochemical changes compared with patients who were only depressed, suggesting a propensity of diabetic subjects to develop depressive biochemical and electrophysiological traits. Alterations of the N1/P2 component of the IDAEP reflect an impaired cortical activity associated with anomalies of brain serotonergic neurotransmission (Hegerl and Juckel 1993;Juckel et al 1997; Manjarrez et al 2001Manjarrez et al , 2005Manjarrez et al , 2006Manjarrez et al , 2007. Diabetic subjects with depression showed a significantly higher ASF than the other groups, which translates to a more intense cortical reactivity in the presence of a low brain serotonergic tone.…”

5-Hydroxyhexanoic Acid Predicts Early Renal Functional Decline in Type 2 Diabetes Patients with Microalbuminuria

“…The metabolites that were altered significantly were selected according to a variable VIP score of the (O)PLS model and the p values from t tests. These results revealed that 5 metabolites (azelaic acid, adipic acid, 5-hydroxyhexanoic acid, L-pyroglutamic acid, and D-norvaline) with a p value <0.05 and VIP ≥1, and L-tryptophan, which obviously varied in VIP although with p > 0.05, have a significant decrease in T2D patients [29] and play a role in the pathogenesis and development of diabetes, inflammatory diseases, and immunoregulation [30, 31]. They were selected as the best urine metabolites that differed significantly between the groups in this pilot study phase (Table 2).…”