A Study of Tryptophan Metabolism via Serotonin in Ventricular Cerebrospinal Fluid in HIV-1 Infection Using a Neuroendoscopic Technique

Abstract

In this paper we report the study of tryptophan metabolism via serotonin in ventricular CSF in HIV-1 infection in order to investigate the origin of tryptophan metabolites in the human brain. The patients (n=4) were affected with non-communicating hydrocephalus. One of these also was suffering from HIV-1 infection. The CSF was withdrawn from different sites of the cerebral cavity with a neuroendoscopic procedure which allows an accurate exploration of all the cerebral ventricles. The measurement of tryptophan, 5-hydroxytryptophan, serotonin, 5-hydroxyindoleacetic acid, and melatonin was carried out by HPLC with fluorometric detection. In HIV-1 infection the highest concentration of tryptophan is present in the CSF of the choroid plexus; however, the levels are markedly lower than those in hydrocephalic individuals (control group). 5-Hydroxytryptophan CSF content is higher in HIV-1 infection than in hydrocephalic controls in all districts examined. Regarding serotonin, a great difference appears in the choroid plexus and in the pituitary recess between the HIV-1 infected patient and the control group. The values of 5-hydroxyindoleacetic acid are much lower in the CSF of the HIV-1 infected patient than in hydrocephalic controls. Melatonin levels appear to fluctuate largely but, in the HIV-1 infection, a great variability is present among the sites of CSF withdrawal. The third ventricle contains the highest concentration of melatonin and the choroid plexus and the pituitary recess the lowest. All the melatonin concentrations in HIV-1 infection are largely different than in hydrocephalic controls. This is the first report on the measurement of tryptophan metabolites via serotonin in ventricular CSF in HIV-1 infection.

Neopterin Relates to Lifetime Depression in Older Adults With HIV on Suppressive Antiretroviral Therapy

“…Elevated neopterin is consistently correlated with conversion of tryptophan to kynurenine, resulting in less serotonin synthesis. Plasma and CSF levels of serotonin are reduced in PWH [44][45][46] and greater tryptophan degradation (indexed by kynurenine/tryptophan ratios) has been linked to depression 20,47 and impulsivity/risk-taking 48 in PWH. In addition to serotonergic deficiencies, neopterin also correlates with decelerated conversion of phenylalanine to tyrosine, resulting in less dopamine synthesis.…”

Melatonin for the Early Treatment of COVID-19: A Narrative Review of Current Evidence and Possible Efficacy

“…Melatonin administration not only reduced the mortality rate from these viruses, but also significantly postponed onset of disease ( 10 ), providing further evidence of melatonin use as treatment in a number of viral diseases. There is some research concerning the effects of melatonin on retroviruses such as HIV and murine model retroviruses such as LP-BM5 and Ts1, though these do not seem to have many pertinent similarities to COVID-19 ( 32 , 33 , 34 , 35 ).…”

Potential Mechanism for HIV-Associated Depression: Upregulation of Serotonin Transporters in SIV-Infected Macaques Detected by 11C-DASB PET

“…In another study, disruption of cytoskeletal genes and dysregulation of somatostatin were found to be part of the pathologic process of major depressive disorder (MDD) in the setting of HIV (3). Tryptophan metabolism dysregulation is also suspected to play a role (4, 5).…”