•Acute restraint stress decreases whole brain glucose metabolism in mice.•Effects of restraint stress in the brain 18F-FDG uptake are time and sex-dependent.•Restraint stress alters glucose uptake in ...the blood, liver and right adrenal of females.
Stress has been considered as a risk factor for the development and aggravation of several diseases. The hypothalamic-pituitary-adrenal axis (HPA) is one of the main actors for the stress response and homeostasis maintenance. Positron emission tomography (PET) has been used to evaluate neuronal activity and to study brain regions that may be related to the HPA axis response. Since neuroimaging is an important tool in detecting neuroendocrine-related changes, we used fluorodeoxyglucose-18 (18F-FDG) and positron emission microtomography (microPET) to evaluate sexual differences in the glucose brain metabolism after 10, 30 and 40 min of acute stress in Balb/c mice. We also investigated the effects of restraint stress in blood, liver and adrenal gland 18F-FDG biodistribution using a gamma counter. A decreased glucose uptake in the whole brain in both females and males was found. Additionally, there were time and sex-dependent alterations in the 18F-FDG uptake after restraint stress in specific brain regions, indicating that males could be more vulnerable to the short-term effects of acute stress. According to the gamma counter biodistribution, only females showed a significant decreased glucose uptake in the blood, liver and right adrenal after restraint stress. In addition, in comparisons between the sexes, males showed a decreased glucose uptake in the whole brain and in several brain regions compared to females. In conclusion, exposure to acute restraint stress resulted in significant decreased glucose metabolism in the brain, with particular effects in different regions and organs in a sex-specific manner.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Based on preclinical findings, cellular therapy has become a promising therapeutic approach for neonatal hypoxia–ischemia (HI). However, before translation into the clinical setting, new and ...effective routes of cell delivery must be determined. Intra-arterial (IA) delivery is an attractive route of cellular administration but has never been used in neonatal HI rats. Aims: In this study, we investigated the feasibility of IA transplantation of human umbilical cord blood (HUCB) mononuclear cells for the treatment of long-term behavior dysfunction and brain lesion after neonatal HI. Main methods: Seven-day-old rats were subjected to a HI model and the animals received HUCB mononuclear cells into the left common carotid artery 24h after HI insult. Key findings: At 9weeks post-HI, intra-arterially transplanted HUCB mononuclear cells significantly improved learning and long-term spatial memory impairments when evaluated by the Morris water maze paradigm. There was no effect of neonatal HI insult or IA procedure on body weight and on motor coordination and balance when evaluated by the accelerating rotarod test. Cellular transplantation by the IA route did not restore neonatal HI-induced brain damage according to stereological volume assessment. Furthermore, HUCB mononuclear cells were tracked in the injured brain and peripheral organs of HI transplanted-rats by nested polymerase chain reaction analysis at different time points. Significance: Our findings contribute to the translational knowledge of cell based-therapy in neonatal HI and demonstrate for the first time that IA transplantation into rat pups is a feasible route for cellular delivery and prevents long-term cognitive deficits induced by experimental neonatal HI.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Major depressive disorder (MDD) leads to pervasive changes in the health of afflicted patients. Despite advances in the understanding of MDD and its treatment, profound innovation is needed to ...develop fast-onset antidepressants with higher effectiveness. When acutely administered, the endogenous nucleoside guanosine (GUO) shows fast-onset antidepressant-like effects in several mouse models, including the olfactory bulbectomy (OBX) rodent model. OBX is advocated to possess translational value and be suitable to assess the time course of depressive-like behavior in rodents. This study aimed at investigating the long-term behavioral and neurochemical effects of GUO in a mouse model of depression induced by bilateral bulbectomy (OBX). Mice were submitted to OBX and, after 14 days of recovery, received daily (ip) administration of 7.5 mg/kg GUO or 40 mg/kg imipramine (IMI) for 45 days. GUO and IMI reversed the OBX-induced hyperlocomotion and recognition memory impairment, hippocampal BDNF increase, and redox imbalance (ROS, NO, and GSH levels). GUO also mitigated the OBX-induced hippocampal neuroinflammation (IL-1, IL-6, TNF-α, INF-γ, and IL-10). Brain microPET imaging (
18
FFDG) shows that GUO also prevented the OBX-induced increase in hippocampal FDG metabolism. These results provide additional evidence for GUO antidepressant-like effects, associated with beneficial neurochemical outcomes relevant to counteract depression.
Abstract Hypoxia–ischemia (HI) is a common cause of neonatal brain damage with lifelong morbidities in which current therapies are limited. In this study, we investigated the effect of neuropeptide ...NAP (NAPVSIPQ) on early cerebral oxidative stress, long-term neurological function and brain injury after neonatal HI. Seven-day-old rat pups were subjected to an HI model by applying a unilateral carotid artery occlusion and systemic hypoxia. The animals were randomly assigned to groups receiving an intraperitoneal injection of NAP (3 μg/g) or vehicle immediately (0 h) and 24 h after HI. Brain DNA damage, lipid peroxidation and reduced glutathione (GSH) content were determined 24 h after the last NAP injection. Cognitive impairment was assessed on postnatal day 60 using the spatial version of the Morris water maze learning task. Next, the animals were euthanized to assess the cerebral hemispheric volume using the Cavalieri principle associated with the counting point method. We observed that NAP prevented the acute HI-induced DNA and lipid membrane damage and also recovered the GSH levels in the injured hemisphere of the HI rat pups. Further, NAP was able to prevent impairments in learning and long-term spatial memory and to significantly reduce brain damage up to 7 weeks following the neonatal HI injury. Our findings demonstrate that NAP confers potent neuroprotection from acute brain oxidative stress, long-term cognitive impairment and brain lesions induced by neonatal HI through, at least in part, the modulation of the glutathione-mediated antioxidant system.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Neonatal seizures in which hypoxic-ischemic encephalopathy is the main triggering etiology have a challenging diagnosis and limited efficacy of treatment. NAP (NAPVSIPQ) has shown extensive ...neuroprotective and antioxidant capacity in vitro and in vivo . To evaluate its neuroprotective role in the context of seizures associated with perinatal hypoxia, we assessed the integrity of DNA and lipid membranes as well as the redox status in the hippocampus of 10-day-old rats exposed to hypoxia-induced seizures (HS) with and without NAP treatment. Rats were exposed to transient global hypoxia (12 min exposure to 5–7% O2 was able to induce electrographic seizures) or room air with subsequent intraperitoneal NAP (0.03, 0.3 or 3 μg/g) or vehicle administration. Results showed elevated DNA damage immediately after the insult until 72 h post-HS, while oxidized bases were only detected 3, 6 and 24 h later. In addition, thiobarbituric acid reactive species peaked at 6 h in parallel with decreased levels of reduced glutathione between 3 and 72 h post-HS insult. Our findings expand on the knowledge about the time course of HS-induced oxidative damage and demonstrate for the first time that a single NAP injection dose-dependently prevents HS-induced oxidative damage to DNA and lipid membranes, in correlation with modulation of the glutathione system. Hence, NAP may represent a promising therapeutic strategy for avoiding HS-induced oxidative damage.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Este artigo trata sobre uma revisão bibliográfica acerca da percepção da dor e como esta afeta a motivação e os estados psicológicos em jogadores de futebol. Para tanto, foi realizada uma pesquisa ...narrativa de cunho bibliográfico utilizando as bases eletrônicas PubMed, Scielo e Capes. O objetivo geral deste estudo foi identificar a relação existente entre a percepção da dor e a motivação em jogadores de futebol. Com os resultados, percebeu-se que, mesmo com dor, os atletas, em casos de suportá-la, evitam informá-la à comissão técnica por medo de ficarem de fora do elenco (perdendo a titularidade e relevância). Além disso, os atletas são muito afetados na motivação, principalmente no que tange os fatores psicológicos em momentos de lesões, chegando a casos de depressão e estresse quando ficam longos períodos afastados. Conclui-se, então, que os atletas se motivam intrinsecamente em sua maioria. O treinador, bem como suas metodologias, são os principais fatores de motivação extrínseca A percepção subjetiva exacerbada da dor é um dos fatores desmotivacionais, principalmente em casos de lesões, o que ocorre em função do caráter heroico que se cria em torno do atleta e da alta competitiva de cobrança de rendimento. Justamente por isso, deve ser feito um acompanhamento psicológico com estes jogadores tanto de divisões maiores quanto menores, buscando auxiliá-los sempre, não somente em momentos de lesão. Sugere-se ainda que sejam conduzidos mais estudos na área para uma maior compreensão do fenômeno estudado.
Este artigo trata sobre uma revisão bibliográfica acerca da percepção da dor e como esta afeta a motivação e os estados psicológicos em jogadores de futebol. Para tanto, foi realizada uma pesquisa ...narrativa de cunho bibliográfico utilizando as bases eletrônicas PubMed, Scielo e Capes. O objetivo geral deste estudo foi identificar a relação existente entre a percepção da dor e a motivação em jogadores de futebol. Com os resultados, percebeu-se que, mesmo com dor, os atletas, em casos de suportá-la, evitam informá-la à comissão técnica por medo de ficarem de fora do elenco (perdendo a titularidade e relevância). Além disso, os atletas são muito afetados na motivação, principalmente no que tange os fatores psicológicos em momentos de lesões, chegando a casos de depressão e estresse quando ficam longos períodos afastados. Conclui-se, então, que os atletas se motivam intrinsecamente em sua maioria. O treinador, bem como suas metodologias, são os principais fatores de motivação extrínseca A percepção subjetiva exacerbada da dor é um dos fatores desmotivacionais, principalmente em casos de lesões, o que ocorre em função do caráter heroico que se cria em torno do atleta e da alta competitiva de cobrança de rendimento. Justamente por isso, deve ser feito um acompanhamento psicológico com estes jogadores tanto de divisões maiores quanto menores, buscando auxiliá-los sempre, não somente em momentos de lesão. Sugere-se ainda que sejam conduzidos mais estudos na área para uma maior compreensão do fenômeno estudado. Palavras-chave: Dor. Motivação. Futebol. Neurociência. Pain perception and motivation in football players: neuroscience contributions This article is about a bibliographic review about the perception of pain and how it affects motivation and psychological states in football players. For this, a narrative research of bibliographic nature was carried out using the electronic databases PubMed, Scielo and Capes. The general objective of this study was to identify the relationship between pain perception and motivation in football players. With the results, it was realized that, even in pain, athletes, in cases of enduring it, avoid informing the technical committee for fear of being left out of the squad (losing title and relevance). In addition, athletes are very affected in motivation, especially with regard to psychological factors in times of injury, reaching cases of depression and stress when they are away for long periods. It is concluded, then, that the athletes are mostly intrinsically motivated. The coach, as well as his methodologies, are the main factors of extrinsic motivation The subjective exacerbated perception of pain is one of the demotivational factors, mainly in cases of injuries, which occurs due to the heroic character that is created around the athlete and the competitive high rate of revenue collection. Precisely for this reason, psychological monitoring must be carried out with these players, both from larger and smaller divisions, seeking to always help them, not only in times of injury. It is also suggested that further studies be conducted in the area for a better understanding of the studied phenomenon. Key words: Pain. Motivation. Football. Neuroscience.
Voltage-gated calcium channels (VGCCs) play a critical role in neuroinflammatory diseases, such as multiple sclerosis (MS). CTK 01512-2 is a recombinant version of the peptide Phα1β derived from the ...spider
Phoneutria nigriventer
, which inhibits N-type VGCC/TRPA1-mediated calcium influx. We investigated the effects of this molecule in the mouse model of experimental autoimmune encephalomyelitis (EAE). The effects of CTK 01512-2 were compared to those displayed by ziconotide—a selective N-type VGCC blocker clinically used for chronic pain—and fingolimod—a drug employed for MS treatment. The intrathecal (i.t.) treatment with CTK 01512-2 displayed beneficial effects, by preventing nociception, body weight loss, splenomegaly, MS-like clinical and neurological scores, impaired motor coordination, and memory deficits, with an efficacy comparable to that observed for ziconotide and fingolimod. This molecule displayed a favorable profile on EAE-induced neuroinflammatory changes, including inflammatory infiltrate, demyelination, pro-inflammatory cytokine production, glial activation, and glucose metabolism in the brain and spinal cord. The recovery of spatial memory, besides a reduction of serum leptin levels, allied to central and peripheral elevation of the anti-inflammatory cytokine IL-10, was solely modulated by CTK 01512-2, dosed intrathecally. The intravenous (i.v.) administration of CTK 01512-2 also reduced the EAE-elicited MS-like symptoms, similarly to that seen in animals that received fingolimod orally. Ziconotide lacked any significant effect when dosed by i.v. route. Our results indicate that CTK 01512-2 greatly improved the neuroinflammatory responses in a mouse model of MS, with a higher efficacy when compared to ziconotide, pointing out this molecule as a promising adjuvant for MS management.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Generalized pain and fatigue are both hallmarks of fibromyalgia, a syndrome with an indefinite etiology. The treatment options for fibromyalgia are currently limited, probably because of its ...intricate pathophysiology. Thus, further basic and clinical research on this condition is currently needed. This study investigated the effects of nociceptin/orphanin FQ (N/OFQ) receptor (NOPr) ligands and the modulation of the NOP system in the preclinical mouse model of reserpine-induced fibromyalgia. The effects of administration of the natural agonist N/OFQ and the selective NOPr antagonists (UFP-101 and SB-612111) were evaluated in fibromyalgia-related symptoms in reserpine-treated mice. The expression of prepronociceptin/orphanin FQ and NOPr was assessed in central and peripheral sites at different time points after reserpine administration. Nociceptin/orphanin FQ displayed dual effects in the behavioral changes in the reserpine-elicited fibromyalgia model. The peptide NOPr antagonist UFP-101 produced analgesic and antifatigue effects, by preventing alterations in brain activity and skeletal muscle metabolism, secondary to fibromyalgia induction. The nonpeptide NOPr antagonist SB-612111 mirrored the favorable effects of UFP-101 in painful and fatigue alterations induced by reserpine. A time-related up- or downregulation of prepronociceptin/orphanin FQ and NOPr was observed in supraspinal, spinal, and peripheral sites of reserpine-treated mice. Our data shed new lights on the mechanisms underlying the fibromyalgia pathogenesis, supporting a role for N/OFQ-NOP receptor system in this syndrome.
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