Absence of the gut microbiota enhances anxiety-like behavior and neuroendocrine response to acute stress in rats.

Background And Aims: Establishment of the gut microbiota is one of the most important events in early life and emerging evidence indicates that the gut microbiota influences several aspects of brain functioning, including reactivity to stress. To better understand how the gut microbiota contributes to a vulnerability to the stress-related psychiatric disorders, we investigated the relationship between the gut microbiota, anxiety-like behavior and HPA axis activity in stress-sensitive rodents. We also analyzed the monoamine neurotransmitters in the brain upper structures involved in the regulation of stress and anxiety.

Early stress leads to effects on estrous cycle and differential responses to stress.

Women are more susceptible than men to stress-related mental disorders. However, few animal studies have been conducted on females. Given the interactions between gonadic hormones and the hypothalamo-pituitary-adrenal (HPA) axis, we hypothesized that the effects of early stress may be different between males and females depending on the state of their estrous cycle.

Isatin binding proteins in rat brain: in situ imaging, quantitative characterization of specific [3H]isatin binding, and proteomic profiling.

Isatin (indole-2,3-dione) is an endogenous indole that has a distinct and discontinuous distribution in the brain and in other mammalian tissues and body fluids. Its output is increased under conditions of stress and anxiety. Its biological targets remain poorly characterized, although [(3)H]isatin binding sites have been demonstrated in various brain structures.

5-hydroxyoxindole, an indole metabolite, is present at high concentrations in brain.

5-Hydroxyoxindole has been identified as a urinary metabolite of indole, which is produced from tryptophane via the tryptophanase activity of gut bacteria. We have demonstrated recently that 5-hydroxyoxindole is an endogenous compound in blood and tissues of mammals, including humans. To date, 5-hydroxyoxindole's role is unknown.

Isatin: role in stress and anxiety.

(Indoledione 2,3) isatin is an endogenous indole found both in mammalian brain and peripheral tissues. Isatin concentration in blood can exceed 1 microM and tissue concentrations vary from < 0.1 to 10 microM.

Natriuretic peptide interaction with [3H]isatin binding sites in rat brain.

Isatin is an endogenous indole, which has a distinct and discontinuous distribution in the brain and exhibits a wide range of physiological and pharmacological effects. In the present study, we have demonstrated that atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) inhibited [3H]isatin binding to rat brain sections and isolated membrane fractions. Isatin itself antagonised not only natriuretic peptide receptor type A (NPR-A) (ANP-stimulation of guanylyl cyclase) but also NPR-C (ANP and CNP mediated inhibition of adenylyl cyclase) signalling.

Inhibition of brain mitochondrial monoamine oxidases by the endogenous compound 5-hydroxyoxindole.

5-Hydroxyoxindole is a recently identified endogenous compound. Its physiological role remains unclear but certain evidence exists, that it may share some regulatory properties with isatin, a known endogenous inhibitor of monoamine oxidase (MAO) type B (MAO-B). In this study several oxidized indoles were tested for their in vitro inhibition of MAO type A (MAO-A) and B of rat brain non-synaptic mitochondria.

Detection and quantification of 5-hydroxyoxindole in mammalian sera and tissues by high performance liquid chromatography with multi-electrode electrochemical detection.

Objective: Since 5-hydroxyoxindole structurally related indole metabolites play different roles in some hepatic and neurologic disorders we found necessary to develop an assay to further investigate the physiologic relevance of this compound.

Methods: We have designed a convenient assay to determine 5-hydroxyoxindole in serum using solid phase extraction and a highly selective High Performance Liquid Chromatography system with multi-Electro Chemical Detection (HPLC-ECD).

Results: We have identified and quantified 5-hydroxyoxindole in various mammalian species.

In situ imaging of specific binding of [3H]isatin in rat brain.

Isatin is an endogenous indole that influences a range of processes both in vivo and in vitro. It has a distinct and discontinuous distribution in the brain, as well as in other mammalian tissues and body fluids. However, the distribution of isatin binding sites in the brain is not known.