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

Introduction: Resveratrol and related polyphenols have therapeutic effects ranging from treatment of depression, Alzheimer's and Parkinson's disease, obesity, diabetes, neurodegeneration and ageing. TRH and TRH-like peptides, with the structure pGlu-X-Pro-NH , where 'X can be any amino acid reside, have reproductive, caloric-restriction-like, anti-ageing, pancreatic-β cell-enhancing, cardiovascular and neuroprotective effects. We hypothesize that TRH and TRH-like peptides are mediators of the therapeutic actions of the resveratrol derivative pterostilbene (PT).

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

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.

The Behavioral Physiology and Antidepressant Mechanisms of Electroconvulsive Shock.

Objective: This study aimed to determine whether the association between antidepressant (AD) and anticonvulsant effects of electroconvulsive therapy constitutes a necessary, causal relationship.

Methods: The rats received corneal kindling to induce an epileptic focus, whereas electroconvulsive shock (ECS) was given antagonistically. The forced swim test (FST; a model of AD efficacy), cumulative kindling scores (indexing epileptogenesis), and clonus duration (measuring anticonvulsant effects) were used to assess the effects of ECS.

Increased TRH and TRH-like peptide release in rat brain and peripheral tissues during proestrus/estrus.

Women are at greater risk for major depression, PTSD, and other anxiety disorders. ERβ-selective agonists for the treatment of these disorders are the focus of pharmacologic development and clinical testing. Estradiol and its metabolites contribute to the neuroprotective effects of this steroid class, particularly in men, due to local conversion of testosterone to estiradiol in key brain regions which are predisposed to neurodegenerative diseases.

Rapid modulation of TRH and TRH-like peptide release in rat brain and peripheral tissues by ghrelin and 3-TRP-ghrelin.

Ghrelin is not only a modulator of feeding and energy expenditure but also regulates reproductive functions, CNS development and mood. Obesity and major depression are growing public health concerns which may derive, in part, from dysregulation of ghrelin feedback at brain regions regulating feeding and mood. We and others have previously reported that thyrotropin-releasing hormone (TRH, pGlu-His-Pro-NH(2)) and TRH-like peptides (pGlu-X-Pro-NH(2), where "X" can be any amino acid residue) have neuroprotective, antidepressant, anti-epileptic, analeptic, anti-ataxic, and anorectic properties.

Rapid modulation of TRH and TRH-like peptide release in rat brain and peripheral tissues by prazosin.

Hyperresponsiveness to norepinephrine contributes to post-traumatic stress disorder (PTSD). Prazosin, a brain-active blocker of α(1)-adrenoceptors, originally used for the treatment of hypertension, has been reported to alleviate trauma nightmares, sleep disturbance and improve global clinical status in war veterans with PTSD. Thyrotropin-releasing hormone (TRH, pGlu-His-Pro-NH(2)) may play a role in the pathophysiology and treatment of neuropsychiatric disorders such as major depression, and PTSD (an anxiety disorder).

Rapid modulation of TRH and TRH-like peptide release in rat brain and peripheral tissues by leptin.

Leptin is not only a feedback modulator of feeding and energy expenditure but also regulates reproductive functions, CNS development and mood. Obesity and major depression are growing public health concerns which may derive, in part, from disregulation of leptin feedback at the level of the hypothalamic feeding centers and mood regulators within the limbic system. Identifying downstream mediators of leptin action may provide therapeutic opportunities.

Rapid modulation of TRH and TRH-like peptide release in rat brain, pancreas, and testis by a GSK-3beta inhibitor.

Antidepressants have been shown to be neuroprotective and able to reverse damage to glia and neurons. Thyrotropin-releasing hormone (TRH) is an endogenous antidepressant-like neuropeptide that reduces the expression of glycogen synthase kinase-3beta (GSK-3beta), an enzyme that hyperphosphorylates tau and is implicated in bipolar disorder, diabetes and Alzheimer's disease. In order to understand the potential role of GSK-3beta in the modulation of depression by TRH and TRH-like peptides and the therapeutic potential of GSK-3beta inhibitors for neuropsychiatric and metabolic diseases, young adult male Sprague-Dawley (SD) rats were (a) injected ip with 1.

TRH and TRH-like peptide expression in rat following episodic or continuous corticosterone.

Sustained abnormalities of glucocorticoid levels have been associated with neuropsychiatric illnesses such as major depression, posttraumatic stress disorder (PTSD), panic disorder, and obsessive compulsive disorder. The pathophysiological effects of glucocorticoids may depend not only on the amount of glucocorticoid exposure but also on its temporal pattern, since it is well established that hormone receptors are down-regulated by continuously elevated cognate hormones. We have previously reported that TRH (pGlu-His-Pro-NH2) and TRH-like peptides (pGlu-X-Pro-NH2) have endogenous antidepressant-like properties and mediate or modulate the acute effects of a single i.

Escitalopram regulates expression of TRH and TRH-like peptides in rat brain and peripheral tissues.

Background: Escitalopram (eCIT) is a highly selective serotonin reuptake inhibitor (SSRI) that can be an effective treatment for a number of neuropsychiatric disorders including major depression. We, and others, have previously reported that thyrotropin-releasing hormone (TRH, pGlu-His-Pro-NH(2)) and TRH-like peptides with the general structure pGlu-X-Pro-NH(2), where 'X' can be any amino acid residue, have neuroprotective, antidepressant, analeptic, arousal, and anti-epileptic effects that could mediate the neuropsychiatric and therapeutic effects of a variety of neurotropic agents. The present work explores the possible mediation of the therapeutic effects of eCIT by TRH and TRH-like peptides.

Lipopolysaccharide modulation of thyrotropin-releasing hormone (TRH) and TRH-like peptide levels in rat brain and endocrine organs.

Lipopolysaccharide (LPS) is a proinflammatory and depressogenic agent whereas thyrotropin-releasing hormone (TRH; pGlu-His-Pro-NH2) is an endogenous antidepressant and neuroprotective peptide. LPS and TRH also have opposing effects on K+ channel conductivity. We hypothesized that LPS can modulate the expression and release of not only TRH but also TRH-like peptides with the general structure pGlu-X-Pro-NH2, where "X" can be any amino acid residue.

Circadian rhythms of TRH-like peptide levels in rat brain.

This is the first report of diurnal variations in the levels of thyrotropin-releasing hormone-like peptides (pGlu-X-Pro-NH(2), where "X" can be any amino acid residue) in brain regions involved in mood regulation. These peptides have neuroprotective and antidepressant-like properties that may help stabilize chronobiologic systems that are often abnormal in neuropsychiatric disease. We hypothesized that diurnal fluctuations in the levels of these neuropeptides are components of the chronobiologic regulation of autonomic, behavioral and emotional states.

Rapid modulation of TRH-like peptides in rat brain by thyroid hormones.

Recent identification of membrane receptors for T4, T3, 3,5-T2, and 3-iodothyronamine that mediate rapid physiologic effects of thyroid hormones suggested that such receptors may supplement the regulation of TRH and TRH-like peptides by nuclear T3 receptors. For this reason 200 g male Sprague-Dawley rats received daily i.p.

TRH-like antidepressant peptide, pyroglutamyltyroslyprolineamide, occurs in rat brain.

We have previously reported the occurrence of pGlu-Glu-Pro-NH(2)(Glu-TRH, EEP), Val-TRH, Tyr-TRH, Leu-TRH, Phe-TRH, and Trp-TRH in rat brain using a combination of HPLC and radioimmunoassays with antibodies that cross-react with the general structure pGlu-X-Pro-NH(2) where 'X' maybe any amino acid residue (Peptides 2004; 25 : 647). This new family of TRH-like peptides, along with TRH (pGlu-His-Pro-NH(2)), has neuroprotective, anticonvulsant, antidepressant, euphoric, anti-amnesic, and analeptic effects. We now report that a combination of affinity chromatography using a rabbit antibody specific for Tyr-TRH and Phe-TRH, along with HPLC and tandem mass spectrometry operating in the multiple reaction monitoring (MRM) mode, provide conclusive evidence for the presence of Tyr-TRH in rat brain.

Valproate modulates TRH receptor, TRH and TRH-like peptide levels in rat brain.

We have tested our hypothesis that alterations in the levels of TRH receptors, and the synthesis and release of tripeptide TRH, and other neurotropic TRH-like peptides mediate some of the mood stabilizing effects of valproate (Valp). We have directly compared the effect of 1 week of feeding two major mood stabilizers, Valp and lithium chloride (LiCl) on TRH binding in limbic and extra-limbic regions of male WKY rats. Valp increased TRH receptor levels in nucleus accumbens and frontal cortex.

Vagus nerve stimulation (VNS) is effective in a rat model of antidepressant action.

Depression is a common but debilitating illness that afflicts a large population and costs the US economy a staggering $40 billion dollars per year. Clinical studies have demonstrated that vagus nerve stimulation (VNS) is an effective treatment for medication-resistant depression. Understanding VNS's antidepressant mechanisms is key to improving the therapy and selecting the best surgical candidates, and demonstration that VNS is effective in a validated test of antidepressant activity allows us to elucidate these mechanisms in a cost-effective manner.

Cocaine regulates TRH-related peptides in rat brain.

Cocaine administration has previously been reported to alter the levels of prepro-TRH mRNA and TRH (pGlu-His-Pro-NH(2)) in the limbic system of rats (J. Neurochem. 60 (1993) 1151).

Role of TRH receptors as possible mediators of analeptic actions of TRH-like peptides.

A large family of TRH-like peptides in the limbic region of rat brain including pGlu-Glu-Pro-NH(2) (EEP), pGlu-Val-Pro-NH(2) (Val(2)-TRH), Leu(2)-TRH, Phe(2)-TRH and Tyr(2)-TRH has recently been discovered. TRH (pGlu-His-Pro-NH(2)) has antidepressant, neuroprotective, analeptic, anticonvulsant, antiamnesic and euphoric properties, and other TRH-like peptides such as EEP exert several of these effects. A new TRH receptor (TRHR2) has been reported which is highly expressed in regions of rat brain that regulate attention and learning, arousal, sleep and processing of sensory information.