The expanding impact of methylglyoxal on behavior-related disorders.

Methylglyoxal (MGO) is a reactive dicarbonyl compound formed as a byproduct of glycolysis. MGO is a major cell-permeant precursor of advanced glycation end products (AGEs), since it readily reacts with basic phospholipids and nucleotides, as well as amino acid residues of proteins, such as arginine, cysteine, and lysine. The AGEs production induced by MGO are widely associated with several pathologies, including neurodegenerative diseases.

Role of heme oxygenase-1 in the antidepressant-like effect of ursolic acid in the tail suspension test.

Objectives: This study investigated the involvement of heme oxygenase-1 (HO-1) in the antidepressant-like effects of ursolic acid (UA), a plant-derived compound with neuroprotective and antidepressant-like properties.

Methods: Mice received intracerebroventricular injections of zinc protoporphyrin IX (ZnPP) or cobalt protoporphyrin IX (CoPP) to inhibit or induce HO-1, respectively, together with effective (0.1 mg/kg, p.

Aerobic exercise ameliorates survival, clinical score, lung inflammation, DNA and protein damage in septic mice.

Background And Objective: Sepsis is a potentially deadly organic dysfunction, and one of the main causes of mortality in intensive care units (ICU). Aerobic exercise (AE) is a preventive intervention in the establishment of inflammatory conditions, such as chronic lung diseases, but its effects on sepsis remain unclear. Therefore, this study aimed to evaluate the effects of AE on health condition, mortality, inflammation, and oxidative damage in an experimental model of pneumosepsis induced by Klebsiella pneumoniae (K.

Protective effects against memory impairment induced by methylglyoxal in mice co‑treated with FPS‑ZM1, an advanced glycation end products receptor antagonist.

Memory impairment is a feature of several diseases and detrimental as aging population have increased worldwide. Sustained advanced glycation end products (AGEs) receptor (RAGE) activation triggers the production of reactive oxygen species and inflammatory response, leading to neuronal dysfunction and neurodegenerative disorders. Methylglyoxal (MGO) is the most relevant and reactive glycating agent in vivo, leading to the formation of AGEs.

Methylglyoxal-Mediated Dopamine Depletion, Working Memory Deficit, and Depression-Like Behavior Are Prevented by a Dopamine/Noradrenaline Reuptake Inhibitor.

Methylglyoxal (MGO) is an endogenous toxin, mainly produced as a by-product of glycolysis that has been associated to aging, Alzheimer's disease, and inflammation. Cell culture studies reported that MGO could impair the glyoxalase, thioredoxin, and glutathione systems. Thus, we investigated the effect of in vivo MGO administration on these systems, but no major changes were observed in the glyoxalase, thioredoxin, and glutathione systems, as evaluated in the prefrontal cortex and the hippocampus of mice.

Fructose Intake Impairs Cortical Antioxidant Defenses Allied to Hyperlocomotion in Middle-Aged C57BL/6 Female Mice.

Recent evidence suggests that young rodents submitted to high fructose (FRU) diet develop metabolic, and cognitive dysfunctions. However, it remains unclear whether these detrimental effects of FRU intake can also be observed in middle-aged mice. Nine months-old C57BL/6 female mice were fed with water (Control) or 10% FRU in drinking water during 12 weeks.

The effect of voluntary wheel running on the antioxidant status is dependent on sociability conditions.

Voluntary wheel running is widely used as a physical activity (PA) model in rodents, but most studies investigate the beneficial effects of this intervention in socially isolated mice. Social isolation stress (SIS) is associated with vulnerability to oxidative stress and reduced mitochondrial activity. Thus, the aim of this study was to investigate the effects of free access to a running wheel for 21 days on the various markers of the cellular redox/antioxidant status as well as mitochondrial function of mice subjected to SIS or maintained in groups of 3 in the homecage.

The role of vitamin C in stress-related disorders.

Stress-related disorders, such as depression and anxiety, present marked deficits in behavioral and cognitive functions related to reward. These are highly prevalent disabling conditions with high social and economic costs. Furthermore, a significant percentage of affected individuals cannot benefit from clinical intervention, opening space for new treatments.

Multiple cellular targets involved in the antidepressant-like effect of glutathione.

A previous study demonstrated that glutathione (GSH) produces specific antidepressant-like effect in the forced swimming test (FST), a predictive test of antidepressant activity. The present study investigated the involvement of multiple cellular targets implicated in the antidepressant-like effect of GSH in the FST. The antidepressant-like effect of GSH (300 nmol/site, icv) lasted up to 3 h when mice were submitted to FST.

Antidepressant-like and pro-neurogenic effects of physical exercise: the putative role of FNDC5/irisin pathway.

Physical exercise has been shown to exert antidepressant effects, but the mechanisms underlying this effect are not completely elucidated. Therefore, we aimed at investigating the antidepressant, pro-neurogenic, and neuroprotective effects of physical exercise and the possible role of FNDC5/irisin for this effect. Treadmill running was used as a protocol of physical exercise (45 min/day/5 days/week for 4 weeks) in female Swiss mice.

Repeated Methylglyoxal Treatment Depletes Dopamine in the Prefrontal Cortex, and Causes Memory Impairment and Depressive-Like Behavior in Mice.

Methylglyoxal (MGO) is a highly reactive dicarbonyl molecule that promotes the formation of advanced glycation end products (AGEs), which are believed to play a key role in a number of pathologies, such as diabetes, Alzheimer's disease, and inflammation. Here, Swiss mice were treated with MGO by intraperitoneal injection to investigate its effects on motor activity, mood, and cognition. Acute MGO treatment heavily decreased locomotor activity in the open field test at higher doses (80-200 mg/kg), an effect not observed at lower doses (10-50 mg/kg).

Subchronic administration of creatine produces antidepressant-like effect by modulating hippocampal signaling pathway mediated by FNDC5/BDNF/Akt in mice.

Creatine has been shown to play a significant role in the pathophysiology and treatment of major depressive disorder (MDD) in preclinical and clinical studies. However, the biological mechanisms underlying its antidepressant effect is still not fully elucidated. This study investigated the effect of creatine (p.

Antidepressant effects of creatine on amyloid β-treated mice: The role of GSK-3β/Nrf pathway.

Alzheimer's disease (AD) is characterized by progressive synaptic dysfunction and neuronal lost in specific brain areas including hippocampus, resulting in memory/learning deficits and cognitive impairments. In addition, non-cognitive symptoms are reported in AD patients, such as anxiety, apathy and depressed mood. The current antidepressant drugs present reduced efficacy to improve depressive symptoms in AD patients.

Locomotor Treadmill Training Promotes Soleus Trophism by Mammalian Target of Rapamycin Pathway in Paraplegic Rats.

Assisted-treadmill training, may be helpful in promoting muscle mass preservation after incomplete spinal cord injury (SCI). However, biological mechanism involved in this process is still not fully understood. This study investigated the effects of locomotor treadmill training on muscle trophism mediated by protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70S6K) in paraplegic rats.

Central irisin administration affords antidepressant-like effect and modulates neuroplasticity-related genes in the hippocampus and prefrontal cortex of mice.

Evidence has indicated that the practice of physical exercise has antidepressant effects that might be associated with irisin release and BDNF signaling. In this study we investigated the effects of the central administration of irisin or BDNF in predictive tests of antidepressant properties paralleled with the gene expression of peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α), fibronectin type III domain-containing protein 5 (FNDC5) and brain-derived neurotrophic factor (BDNF) in the hippocampus and prefrontal cortex of mice. Irisin (0.

The APPswe/PS1A246E mutations in an astrocytic cell line leads to increased vulnerability to oxygen and glucose deprivation, Ca dysregulation, and mitochondrial abnormalities.

Growing evidence suggests a close relationship between Alzheimer's Disease (AD) and cerebral hypoxia. Astrocytes play a key role in brain homeostasis and disease states, while some of the earliest changes in AD occur in astrocytes. We have therefore investigated whether mutations associated with AD increase astrocyte vulnerability to ischemia.

Ursolic acid affords antidepressant-like effects in mice through the activation of PKA, PKC, CAMK-II and MEK1/2.

Background: Ursolic acid has been shown to display antidepressant-like effects in mice through the modulation of monoaminergic systems. In this study, we sought to investigate the involvement of signaling pathways on the antidepressant-like effects of ursolic acid.

Methods: Mice were treated orally with ursolic acid (0.

Evidence for the involvement of heme oxygenase-1 in the antidepressant-like effect of zinc.

Background: Considering that heme oxygenase-1 (HO-1) and the brain-derived neurotrophic factor (BDNF)-mediated pathway are involved in the pathophysiology of depression and that zinc has been shown to exert beneficial effects in the management of depression, this study investigated the influence of these targets on the antidepressant-like effect of zinc.

Methods: Mice were treated with sub-effective or effective doses of zinc chloride (ZnCl, 10mg/kg, po), and 45min later, they received intracerebroventricular (icv) injections of sub-effective doses of either zinc protoporphyrin IX (ZnPP, 10μg/mouse, HO-1 inhibitor), cobalt protoporphyrin IX (CoPP, 0.01μg/mouse, HO-1 inducer) or K-252a (1μg/mouse, TrkB receptor antagonist).

Antidepressant-like effect of pramipexole in an inflammatory model of depression.

Pramipexole (PPX), a dopamine D2/3 receptor preferring agonist, is currently in use for the treatment of Parkinson's disease symptoms and restless legs syndrome. Recently, anti-inflammatory properties of PPX have been shown in an autoimmune model of multiple sclerosis, and case reports indicate PPX ameliorates depressive symptoms. Since peripheral inflammation is known to induce depression-like behavior in rodents, we assessed the potential antidepressant effect of PPX in an inflammatory model of depression induced by LPS.

MPP-Lesioned Mice: an Experimental Model of Motor, Emotional, Memory/Learning, and Striatal Neurochemical Dysfunctions.

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces motor and nonmotor dysfunctions resembling Parkinson's disease (PD); however, studies investigating the effects of 1-methyl-4-phenylpyridinium (MPP), an active oxidative product of MPTP, are scarce. This study investigated the behavioral and striatal neurochemical changes (related to oxidative damage, glial markers, and neurotrophic factors) 24 h after intracerebroventricular administration of MPP (1.8-18 μg/mouse) in C57BL6 mice.

Creatine Prevents Corticosterone-Induced Reduction in Hippocampal Proliferation and Differentiation: Possible Implication for Its Antidepressant Effect.

The benefits of creatine supplementation have been reported in a broad range of central nervous system diseases, including depression, although the mechanisms underlying these effects remain to be understood. In the present study, we investigated the ability of creatine to counteract the morphological and behavioral effects elicited by chronic administration of corticosterone (CORT, 20 mg/kg, p.o.

Atorvastatin Protects from Aβ-Induced Cell Damage and Depressive-Like Behavior via ProBDNF Cleavage.

Intracerebroventricular (icv) amyloid-beta (Aβ) infusion to mice has been demonstrated to cause neurotoxicty and depressive-like behavior and it can be used to evaluate antidepressant and neuroprotective effect of drugs. Atorvastatin is a widely used statin that has demonstrated antidepressant-like effect in predictable animal behavioral models and neuroprotective effect against Aβ infusion. The purpose of this study was to determine the effect of in vivo atorvastatin treatment against Aβ-induced changes in mood-related behaviors and biochemical parameters in ex vivo hippocampal slices from mice.

Guanosine prevents nitroxidative stress and recovers mitochondrial membrane potential disruption in hippocampal slices subjected to oxygen/glucose deprivation.

Guanosine, the endogenous guanine nucleoside, prevents cellular death induced by ischemic events and is a promising neuroprotective agent. During an ischemic event, nitric oxide has been reported to either cause or prevent cell death. Our aim was to evaluate the neuroprotective effects of guanosine against oxidative damage in hippocampal slices subjected to an in vitro ischemia model, the oxygen/glucose deprivation (OGD) protocol.

Agmatine attenuates reserpine-induced oral dyskinesia in mice: Role of oxidative stress, nitric oxide and glutamate NMDA receptors.

Dyskinesia consists in a series of trunk, limbs and orofacial involuntary movements that can be observed following long-term pharmacological treatment in some psychotic and neurological disorders such as schizophrenia and Parkinson's disease, respectively. Agmatine is an endogenous arginine metabolite that emerges as neuromodulator and a promising agent to manage diverse central nervous system disorders by modulating nitric oxide (NO) pathway, glutamate NMDA receptors and oxidative stress. Herein, we investigated the effects of a single intraperitoneal (i.