Rifaximin modulates TRH and TRH-like peptide expression throughout the brain and peripheral tissues of male rats

Abstract

Background The TRH/TRH-R1 receptor signaling pathway within the neurons of the dorsal vagal complex is an important mediator of the brain-gut axis. Mental health and protection from a variety of neuropathologies, such as autism, Attention Deficit Hyperactivity Disorder, Alzheimer’s and Parkinson’s disease, major depression, migraine and epilepsy are influenced by the gut microbiome and is mediated by the vagus nerve. The antibiotic rifaximin (RF) does not cross the gut-blood barrier. It changes the composition of the gut microbiome resulting in therapeutic benefits for traveler’s diarrhea, hepatic encephalopathy, and prostatitis. TRH and TRH-like peptides, with the structure pGlu-X-Pro-NH2, where “X” can be any amino acid residue, have reproduction-enhancing, caloric-restriction-like, anti-aging, pancreatic-β cell-, cardiovascular-, and neuroprotective effects. TRH and TRH-like peptides occur not only throughout the CNS but also in peripheral tissues. To elucidate the involvement of TRH-like peptides in brain-gut-reproductive system interactions 16 male Sprague–Dawley rats, 203 ± 6 g, were divided into 4 groups (n = 4/group): the control (CON) group remained on ad libitum Purina rodent chow and water for 10 days until decapitation, acute (AC) group receiving 150 mg RF/kg powdered rodent chow for 24 h providing 150 mg RF/kg body weight for 200 g rats, chronic (CHR) animals receiving RF for 10 days; withdrawal (WD) rats receiving RF for 8 days and then normal chow for 2 days. Results Significant changes in the levels of TRH and TRH-like peptides occurred throughout the brain and peripheral tissues in response to RF. The number of significant changes in TRH and TRH-like peptide levels in brain resulting from RF treatment, in descending order were: medulla (16), piriform cortex (8), nucleus accumbens (7), frontal cortex (5), striatum (3), amygdala (3), entorhinal cortex (3), anterior (2), and posterior cingulate (2), hippocampus (1), hypothalamus (0) and cerebellum (0). The corresponding ranking for peripheral tissues were: prostate (6), adrenals (4), pancreas (3), liver (2), testis (1), heart (0). Conclusions The sensitivity of TRH and TRH-like peptide expression to RF treatment, particularly in the medulla oblongata and prostate, is consistent with the participation of these peptides in the therapeutic effects of RF.

A resveratrol derivative modulates TRH and TRH‐like peptide expression throughout the brain and peripheral tissues of male rats

“…These changes result from alterations in the biosynthesis and/or release of these tripeptides. 34 These remarkable changes in peptide levels within the piriform cortex are consistent with current knowledge regarding the role of TRH (and TRH-like peptides) as mediators of antidepressant effects in mammalian brain. 32 The antidepressant activity of Tyr-TRH and analeptic effect of Val-TRH correspond with actions of TRH.…”

“…HPLC and RIA procedures, peak identification, and quantitation by co-chromatography with synthetic TRH and TRH-like peptides, relative potency analysis of multiple antibodies to TRH and TRHlike peptides, and mass spectrometry for comparing peak areas have been previously reported in detail. [32][33][34][35][36][37][38][39][40][41][42][43][44][45] Briefly, after boiling, tissues were dried, re-extracted with methanol, dried and defatted by water-ethyl ether partitioning. Dried samples were dissolved in 0.1%trifluroacetic acid (TFA) and loaded onto reverse phaseC18 Sep-Pak cartridges (Water).…”

“…61 Pterostilbene and resveratrol strongly modulate ghrelin and leptin levels while these metabolism-and obesity-related proteins profoundly alter the expression of TRH and TRH-like peptides. 32 Alterations in the gut microbiome in response to modern lifestyles, and ageing 34 suggest the examination of the extent of ghrelin and leptin mediation of PT modulation of TRH and TRH-like peptide expression is warranted.…”

“…33 TRH and TRH-like peptides occur not only throughout the CNS but also peripheral tissues, with particularly high levels in rat and human prostate. 32,34 Resveratrol decreases both serum TSH and hypothalamic TRH mRNA expression in sub-clinically hypothyroid rats. 2 Resveratrol promotes expression of sirtuins (SIRTs).…”

“…The TRH/TRH‐R1 receptor signalling pathway is an important mediator of brain–gut axis communication via the brain medulla 33 . TRH and TRH‐like peptides occur not only throughout the CNS but also peripheral tissues, with particularly high levels in rat and human prostate 32,34 . Resveratrol decreases both serum TSH and hypothalamic TRH mRNA expression in sub‐clinically hypothyroid rats 2 …”