RESUMO
Caffeine is one of the main ergogenic resources used in exercise and sports. Previously, we reported the ergogenic mechanism of caffeine through neuronal A2AR antagonism in the central nervous system [1]. We now demonstrate that the striatum rules the ergogenic effects of caffeine through neuroplasticity changes. Thirty-four Swiss (8-10 weeks, 47 ± 1.5 g) and twenty-four C57BL/6J (8-10 weeks, 23.9 ± 0.4 g) adult male mice were studied behaviorly and electrophysiologically using caffeine and energy metabolism was studied in SH-SY5Y cells. Systemic (15 mg/kg, i.p.) or striatal (bilateral, 15 µg) caffeine was psychostimulant in the open field (p < 0.05) and increased grip efficiency (p < 0.05). Caffeine also shifted long-term depression (LTD) to potentiation (LTP) in striatal slices and increased the mitochondrial mass (p < 0.05) and membrane potential (p < 0.05) in SH-SY5Y dopaminergic cells. Our results demonstrate the role of the striatum in the ergogenic effects of caffeine, with changes in neuroplasticity and mitochondrial metabolism.
Assuntos
Estimulantes do Sistema Nervoso Central , Neuroblastoma , Substâncias para Melhoria do Desempenho , Humanos , Masculino , Camundongos , Animais , Cafeína/farmacologia , Camundongos Endogâmicos C57BL , Estimulantes do Sistema Nervoso Central/farmacologiaRESUMO
Physical exercise attenuates the development of l-3,4-dihydroxyphenylalanine (l-DOPA)-induced dyskinesia (LID) in 6-hydroxydopamine-induced hemiparkinsonian mice through unknown mechanisms. We now tested if exercise normalizes the aberrant corticostriatal neuroplasticity associated with experimental murine models of LID. C57BL/6 mice received two unilateral intrastriatal injections of 6-hydroxydopamine (12 µg) and were treated after 3 wk with l-DOPA/benserazide (25/12.5 mg/kg) for 4 wk, with individualized moderate-intensity running (60%-70% VÌo2peak) or not (untrained). l-DOPA converted the pattern of plasticity in corticostriatal synapses from a long-term depression (LTD) into a long-term potentiation (LTP). Exercise reduced LID severity and decreased aberrant LTP. These results suggest that exercise attenuates abnormal corticostriatal plasticity to decrease LID.
Assuntos
Antiparkinsonianos/toxicidade , Córtex Cerebral/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , Discinesia Induzida por Medicamentos/prevenção & controle , Terapia por Exercício , Levodopa/toxicidade , Plasticidade Neuronal/efeitos dos fármacos , Transtornos Parkinsonianos/tratamento farmacológico , Animais , Benserazida/toxicidade , Córtex Cerebral/fisiopatologia , Corpo Estriado/fisiopatologia , Di-Hidroxifenilalanina/análogos & derivados , Modelos Animais de Doenças , Discinesia Induzida por Medicamentos/etiologia , Discinesia Induzida por Medicamentos/fisiopatologia , Potenciação de Longa Duração/efeitos dos fármacos , Depressão Sináptica de Longo Prazo/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/fisiopatologia , Corrida , Fatores de TempoRESUMO
Ecto-5'-nucleotidase or CD73 is the main source of extracellular adenosine involved in the activation of adenosine A2A receptors, responsible for the ergogenic effects of caffeine. We now investigated the role of CD73 in exercise by comparing female wild-type (WT) and CD73 knockout (KO) mice in a treadmill-graded test to evaluate running power, oxygen uptake (VÌO2), and respiratory exchange ratio (RER) - the gold standards characterizing physical performance. Spontaneous locomotion in the open field and submaximal running power and VÌO2 in the treadmill were similar between CD73-KO and WT mice; VÌO2max also demonstrated equivalent aerobic power, but CD73-KO mice displayed a 43.7 ± 4.2% larger critical power (large effect size, P < 0.05) and 3.8 ± 0.4% increase of maximum RER (small effect size, P < 0.05). Thus, KO of CD73 was ergogenic; i.e., it increased physical performance.
Assuntos
5'-Nucleotidase/deficiência , 5'-Nucleotidase/genética , Teste de Esforço/métodos , Deleção de Genes , Condicionamento Físico Animal/métodos , Condicionamento Físico Animal/fisiologia , Animais , Feminino , Camundongos , Camundongos KnockoutRESUMO
Parkinson's disease (PD), the second-most prevalent neurodegenerative disease, is primarily characterized by neurodegeneration in the substantia nigra pars compacta, resulting in motor impairment. Loss-of-function mutations in parkin are the major cause of the early onset familial form of the disease. Although rodents deficient in parkin (parkin(-/-) ) have some dopaminergic system dysfunction associated with central oxidative stress and energy metabolism deficiencies, these animals only display nigrostriatal pathway degeneration under inflammatory conditions. This study investigated the impact of the inflammatory stimulus induced by lypopolisaccharide (LPS) on tetrahydrobiopterin (BH4) synthesizing enzymes (de novo and salvage pathways), since this cofactor is essential for dopamine synthesis. The mitochondrial content and architecture was investigated in the striatum of LPS-exposed parkin(-/-) mice. As expected, the LPS (0.33 mg/kg; i.p.) challenge compromised spontaneous locomotion and social interaction with juvenile parkin(-/-) and WT mice. Moreover, the genotype impacted the kinetics of the investigation of the juvenile. The inflammatory scenario did not induce apparent changes in mitochondrial ultrastructure; however, it increased the quantity of mitochondria, which were of smaller size, and provoked the perinuclear distribution of the organelle. Furthermore, the BH4 de novo biosynthetic pathway failed to be up-regulated in the LPS challenge, a well-known stimulus for its activation. The LPS treatment increased sepiapterin reductase (SPR) expression, suggesting compensation by the salvage pathway. This might indicate that dopamine synthesis is compromised in parkin(-/-) mice under inflammatory conditions. Finally, this scenario impaired the striatal expression of the transcription factor BDNF, possibly favoring cell death.
Assuntos
Biopterinas/análogos & derivados , Corpo Estriado/metabolismo , Ubiquitina-Proteína Ligases/genética , Oxirredutases do Álcool/metabolismo , Animais , Comportamento Animal , Biopterinas/biossíntese , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Corpo Estriado/efeitos dos fármacos , Dopamina/metabolismo , Lipopolissacarídeos/farmacologia , Locomoção , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia Eletrônica de Transmissão , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Plasticidade Neuronal/fisiologia , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Doença de Parkinson/veterinária , Ubiquitina-Proteína Ligases/deficiência , Regulação para Cima/efeitos dos fármacosRESUMO
Neopterin is found at increased levels in biological fluids from individuals with inflammatory disorders. The biological role of this pteridine remains undefined; however, due to its capacity to increase hemeoxygenase-1 content, it has been proposed as a protective agent during cellular stress. Therefore, we investigated the effects of neopterin on motor, emotional and memory functions. To address this question, neopterin (0.4 and/or 4pmol) was injected intracerebroventricularly before or after the training sessions of step-down inhibitory avoidance and fear conditioning tasks, respectively. Memory-related behaviors were assessed in Swiss and C57BL/6 mice, as well as in Wistar rats. Moreover, the putative effects of neopterin on motor and anxiety-related parameters were addressed in the open field and elevated plus-maze tasks. The effects of neopterin on cognitive performance were also investigated after intraperitoneal lipopolysaccharide (LPS) administration (0.33mg/kg) in interleukin-10 knockout mice (IL-10(-/-)). It was consistently observed across rodent species that neopterin facilitated aversive memory acquisition by increasing the latency to step-down in the inhibitory avoidance task. This effect was related to a reduced threshold to generate the hippocampal long-term potentiation (LTP) process, and reduced IL-6 brain levels after the LPS challenge. However, neopterin administration after acquisition did not alter the consolidation of fear memories, neither motor nor anxiety-related parameters. Altogether, neopterin facilitated cognitive processes, probably by inducing an antioxidant/anti-inflammatory state, and by facilitating LTP generation. To our knowledge, this is the first evidence showing the cognitive enhancer property of neopterin.
Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Condicionamento Clássico/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Inibição Psicológica , Potenciação de Longa Duração/efeitos dos fármacos , Consolidação da Memória/efeitos dos fármacos , Neopterina/farmacologia , Nootrópicos/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Medo/efeitos dos fármacos , Injeções Intraventriculares , Interleucina-10 , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neopterina/administração & dosagem , Nootrópicos/administração & dosagem , Ratos , Ratos WistarAssuntos
Tolerância ao Exercício , Exercício Físico , Terapia por Exercício , Feminino , Humanos , Masculino , Caracteres SexuaisRESUMO
This study sought to assess how post-game creatine kinase (CK) levels correlate with the number of sprints and the impact of the ACTN3 polymorphism on this response. This research constituted a descriptive/observational, retrospective cross-sectional study. DNA was extracted from blood samples for ACTN3 polymorphism genotyping. CK was measured 48 h after official matches, and the number of sprints (>19 km/h) was tracked using Global Positioning System (GPS) technology. The main cohort included 23 professional soccer players from the top tier of the Brazilian Championship. We analyzed 115 GPS + CK data sets. The replication cohort comprised 18 professional soccer players from the First Division of the Championship, had the same methodology applied, and featured a total of 90 GPS (sprints > 25.2 km/h) + CK data sets. For the main cohort, a significant positive correlation was seen between the number of sprints and the CK levels (p = 0.009). Athletes with the ACTN3 RR genotype had higher CK levels as more sprints were performed during the match (p = 0.017). However, the relationship was not found for X allele carriers (p > 0.05). For the replication cohort, there was a near-significant correlation between CK levels and the number of sprints (p = 0.05), and RR individuals showed a significant association (p = 0.01), whereas X allele carriers did not (p = 0.06). A greater number of sprints during matches is linked to higher CK levels, primarily among players with the ACTN3 RR genotype, which is potentially due to an increased presence of type II muscle fibers. These findings were replicated for both cohorts of elite Brazilian soccer players, emphasizing the importance of genetic factors in injury prevention.
Assuntos
Actinina , Creatina Quinase , Corrida , Futebol , Humanos , Actinina/genética , Brasil , Masculino , Creatina Quinase/sangue , Creatina Quinase/genética , Adulto , Atletas , Desempenho Atlético , Estudos Transversais , Estudos Retrospectivos , Genótipo , Polimorfismo de Nucleotídeo Único , Adulto Jovem , Polimorfismo GenéticoRESUMO
Introduction: Caffeine and the selective A2A receptor antagonist SCH58261 both have ergogenic properties, effectively reducing fatigue and enhancing exercise capacity. This study investigates in male Swiss mice the interaction between adenosine A2A receptors and dopamine D2 receptors controlling central fatigue, with a focus on the striatum where these receptors are most abundant. Methods: We employed DPCPX and SCH58261 to antagonize A1 and A2A receptors, caffeine as a non-competitive antagonist for both receptors, and haloperidol as a D2 receptor antagonist; all compounds were tested upon systemic application and caffeine and SCH58261 were also directly applied in the striatum. Behavioral assessments using the open field, grip strength, and treadmill tests allowed estimating the effect of treatments on fatigue. Results and discussion: The results suggested a complex interplay between the dopamine and adenosine systems. While systemic DPCPX had little effect on motor performance or fatigue, the application of either caffeine or SCH58261 was ergogenic, and these effects were attenuated by haloperidol. The intra-striatal administration of caffeine or SCH58261 was also ergogenic, but these effects were unaffected by haloperidol. These findings confirm a role of striatal A2A receptors in the control of central fatigue but suggest that the D2 receptor-mediated control of the ergogenic effects of caffeine and of A2A receptor antagonists might occur outside the striatum. This prompts the need of additional efforts to unveil the role of different brain regions in the control of fatigue.
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OBJECTIVE: This study aimed to investigate the effects of an 8-wk face-to-face rehabilitation program on subjects with persistent symptoms of COVID-19 compared with a remote monitoring group. DESIGN: This is clinical, nonrandomized, controlled, and open study. The face-to-face supervised rehabilitation lasted eight consecutive weeks, twice a week. The remote monitoring group received health guidance. The allocation was carried out by preference because of the emergency period without vaccination during the pandemic. Fatigue, dyspnea (Pulmonary Functional Status and Dyspnea Questionnaire), and exercise capacity (Incremental Shuttle Walk Test) were the primary outcome measures. Lung function, functional status (Post-COVID-19 Functional Status), symptoms of anxiety and depression (Hospital Anxiety and Depression Scale), attention (d2-R), memory (Rey's Auditory-Verbal Learning Test), handgrip strength, and knee extensor strength were secondary outcome measures. RESULTS: Thirty-seven subjects (24.3% hospitalized) completed the baseline and final assessment, rehabilitation ( n = 22, 40.8 [SD, 10.0] yrs, 54.5% female), or remote guidance ( n = 15, 45.4 [SD, 10.5] yrs, 40% female). Both groups showed improved fatigue and exercise capacity. Exercise rehabilitation improved dyspnea, anxiety, attention, and short-term memory. CONCLUSIONS: Rehabilitation is essential for dyspnea in subjects with persistent symptoms of COVID-19 while fatigue naturally reverses.
Assuntos
COVID-19 , Doença Pulmonar Obstrutiva Crônica , Feminino , Humanos , Masculino , Brasil/epidemiologia , COVID-19/complicações , Dispneia/etiologia , Tolerância ao Exercício , Fadiga/etiologia , Força da Mão , Doença Pulmonar Obstrutiva Crônica/reabilitação , Qualidade de Vida , Adulto , Pessoa de Meia-IdadeRESUMO
While manganese (Mn) is essential for proper central nervous system (CNS) development, excessive Mn exposure may lead to neurotoxicity. Mn preferentially accumulates in the basal ganglia, and in adults it may cause Parkinson's disease-like disorder. Compared to adults, younger individuals accumulate greater Mn levels in the CNS and are more vulnerable to its toxicity. Moreover, the mechanisms mediating developmental Mn-induced neurotoxicity are not completely understood. The present study investigated the developmental neurotoxicity elicited by Mn exposure (5, 10 and 20 mg/kg; i.p.) from postnatal day 8 to PN27 in rats. Neurochemical analyses were carried out on PN29, with a particular focus on striatal alterations in intracellular signaling pathways (MAPKs, Akt and DARPP-32), oxidative stress generation and cell death. Motor alterations were evaluated later in life at 3, 4 or 5 weeks of age. Mn exposure (20 mg/kg) increased p38(MAPK) and Akt phosphorylation, but decreased DARPP-32-Thr-34 phosphorylation. Mn (10 and 20 mg/kg) increased caspase activity and F2-isoprostane production (a biological marker of lipid peroxidation). Paralleling the changes in striatal biochemical parameters, Mn (20 mg/kg) also caused motor impairment, evidenced by increased falling latency in the rotarod test, decreased distance traveled and motor speed in the open-field test. Notably, the antioxidant Trolox™ reversed the Mn (20 mg/kg)-dependent augmentation in p38(MAPK) phosphorylation and reduced the Mn (20 mg/kg)-induced caspase activity and F2-isoprostane production. Trolox™ also reversed the Mn-induced motor coordination deficits. These findings are the first to show that long-term exposure to Mn during a critical period of neurodevelopment causes motor coordination dysfunction with parallel increment in oxidative stress markers, p38(MAPK) phosphorylation and caspase activity in the striatum. Moreover, we establish Trolox™ as a potential neuroprotective agent given its efficacy in reversing the Mn-induced neurodevelopmental effects.
Assuntos
Antioxidantes/farmacologia , Gânglios da Base/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Cromanos/farmacologia , Intoxicação por Manganês/tratamento farmacológico , Atividade Motora/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fatores Etários , Animais , Animais Recém-Nascidos , Gânglios da Base/metabolismo , Gânglios da Base/fisiopatologia , Caspases/metabolismo , Modelos Animais de Doenças , Ativação Enzimática , Feminino , Masculino , Intoxicação por Manganês/etiologia , Intoxicação por Manganês/metabolismo , Intoxicação por Manganês/fisiopatologia , Intoxicação por Manganês/psicologia , Fosforilação , Ratos , Ratos Wistar , Teste de Desempenho do Rota-Rod , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
BACKGROUND: Increased circulating endocannabinoids levels are typically associated with aerobic exercise. This phenomenon is associated with a "runner's high," a state of euphoria and well-being experienced after a long exercise. We will provide in this review a transparent and standardized methodology following the PRISMA-P and Cochrane Handbook for Systematic Reviews of Interventions for conducting a systematic review and meta-analysis for synthesizing the available evidence about the effects of physical activity on the circulating levels of AEA and 2-AG endocannabinoids in healthy subjects. METHODS: A multi-disciplinary team with basic and clinical expertise in exercise science developed this protocol. PubMed, EMBASE, Web of Science, CINAHL, SPORTDiscus, and Scopus will be the databases. A health sciences librarian was consulted in the development of the research. Search strategies will combine MeSH terms and free text words, including "exercise," "exercise, physical," "exercise training," "physical activity," "endocannabinoids," "2-arachidonoyl-glycerol," "glyceryl 2-arachidonate," "2-AG," "anandamide," "AEA," "n-arachidonoylethanolamide," "adult," "young adult," and "middle-aged." We will select experimental or quasi-experimental studies published through December 2021. The selection of studies, data extraction, assessment of the risk of bias, and the quality of evidence will be carried out in a paired and independent manner, and the consistency will be assessed using the statistics of Cohen Kappa. Methodological quality will be assessed using the Revised Cochrane risk of bias tool for randomized trials (RoB 2) and the Risk Of Bias In Nonrandomized Studies of Interventions (ROBINS-I) risk tool. We will use the Grading of Recommendations Assessment, Development, and Evaluation to assess the quality of the evidence, χ2 and I2 tests for heterogeneity, funnel plots, and the Egger test for publication bias. A meta-analysis for each data comparison will be performed whenever possible to determine the effect of physical activity on endocannabinoids' circulating levels. DISCUSSION: This systematic review and meta-analysis will provide an overview of the evidence about physical activity over AEA and 2-AG endocannabinoids, including comparability of variables between studies, critical interpretation of results, and use of accurate statistical techniques. The endocannabinoid is molecules by which muscles communicate with other tissues and organs, mediating the beneficial effects of exercise on health and performance, including increased glucose uptake, improved insulin action, and mitochondrial biogenesis. They are essential to exercise. Thus, this study will review the acute effect of physical exercise on circulating levels of endocannabinoids in healthy individuals. The results of this study will potentially be transferred to doctors, health professionals, and legislators to guide their decision making, as well as will improve future research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020202886 .
Assuntos
Endocanabinoides , Exercício Físico , Humanos , Metanálise como Assunto , Pessoa de Meia-Idade , Literatura de Revisão como Assunto , Revisões Sistemáticas como Assunto , Adulto JovemRESUMO
Physical exercise and smoking are environmental factors that generally cause opposite health-promoting adaptations. Both physical exercise and smoking converge on mitochondrial adaptations in various tissues, including the pro-oxidant nervous system. Here, we analyzed the impact of cigarette smoking on exercise-induced brain mitochondrial adaptations in the hippocampus and pre-frontal cortex of adult mice. The animals were exposed to chronic cigarette smoke followed by 8 weeks of moderate-intensity physical exercise that increased mitochondrial activity in the hippocampus and pre-frontal cortex in the non-smoker mice. However, mice previously exposed to cigarette smoke did not present these exercise-induced mitochondrial adaptations. Our results suggest that smoking can inhibit some brain health-promoting changes induced by physical exercise.
Assuntos
Encéfalo/fisiologia , Mitocôndrias/fisiologia , Nicotiana , Condicionamento Físico Animal , Fumaça , Animais , CamundongosRESUMO
There is considerable evidence showing that the neurodegenerative processes that lead to sporadic Parkinson's disease (PD) begin many years before the appearance of the characteristic motor symptoms and that impairments in olfactory, cognitive and motor functions are associated with time-dependent disruption of dopaminergic neurotransmission in different brain areas. Midkine is a 13-kDa retinoic acid-induced heparin-binding growth factor involved in many biological processes in the central nervous system such as cell migration, neurogenesis and tissue repair. The abnormal midkine expression may be associated with neurochemical dysfunction in the dopaminergic system and cognitive impairments in rodents. Here, we employed adult midkine knockout mice (Mdk(-/-)) to further investigate the relevance of midkine in dopaminergic neurotransmission and in olfactory, cognitive and motor functions. Mdk(/-) mice displayed pronounced impairments in their olfactory discrimination ability and short-term social recognition memory with no gross motor alterations. Moreover, the genetic deletion of midkine decreased the expression of the enzyme tyrosine hydroxylase in the substantia nigra reducing partially the levels of dopamine and its metabolites in the olfactory bulb and striatum of mice. These findings indicate that the genetic deletion of midkine causes a partial loss of dopaminergic neurons and depletion of dopamine, resulting in olfactory and memory deficits with no major motor impairments. Therefore, Mdk(-/-) mice may represent a promising animal model for the study of the early stages of PD and for testing new therapeutic strategies to restore sensorial and cognitive processes in PD.
Assuntos
Citocinas/deficiência , Modelos Animais de Doenças , Deleção de Genes , Fator de Crescimento Neural/deficiência , Doença de Parkinson/genética , Doença de Parkinson/patologia , Animais , Encéfalo/patologia , Encéfalo/fisiologia , Citocinas/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Midkina , Fator de Crescimento Neural/genética , Doença de Parkinson/metabolismo , Reconhecimento Psicológico/fisiologia , Olfato/genéticaRESUMO
We have recently demonstrated that rodents treated intranasally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) suffered impairments in olfactory, cognitive and motor functions associated with time-dependent disruption of dopaminergic neurotransmission in different brain structures conceivably analogous to those observed during different stages of Parkinson's disease (PD). On the other hand, the proanthocyanidin-rich fraction (PRF) obtained from the bark of Croton celtidifolius Baill (Euphorbiaceae), a tree frequently found in the Atlantic forest in south Brazil, has been described to have several neurobiological activities including antioxidant and anti-inflammatory properties, which may be of interest in the treatment of PD. The present data indicated that the pretreatment with PRF (10 mg/kg, i.p.) during five consecutive days was able to prevent mitochondrial complex-I inhibition in the striatum and olfactory bulb, as well as a decrease of the enzyme tyrosine hydroxylase expression in the olfactory bulb and substantia nigra of rats infused with a single intranasal administration of MPTP (1 mg/nostril). Moreover, pretreatment with PRF was found to attenuate the short-term social memory deficits, depressive-like behavior and reduction of locomotor activity observed at different periods after intranasal MPTP administration in rats. Altogether, the present findings provide strong evidence that PRF from C. celtidifolius may represent a promising therapeutic tool in PD, thus being able to prevent both motor and non-motor early symptoms of PD, together with its neuroprotective potential.
Assuntos
Croton/química , Fármacos Neuroprotetores/farmacologia , Transtornos Parkinsonianos/tratamento farmacológico , Extratos Vegetais/farmacologia , Proantocianidinas/farmacologia , Administração Intranasal , Animais , Modelos Animais de Doenças , Masculino , Fármacos Neuroprotetores/administração & dosagem , Extratos Vegetais/administração & dosagem , Proantocianidinas/uso terapêutico , Ratos , Ratos WistarRESUMO
Glucose-dependent insulinotropic polypeptide (GIP) is a 42-amino acid hormone, secreted from the enteroendocrine K cells, which has insulin-releasing and extra-pancreatic actions. GIP and its receptor present a widespread distribution in the mammalian brain where they have been implicated with synaptic plasticity, neurogenesis, neuroprotection and behavioral alterations. This review attempts to provide a comprehensive picture of the role of GIP in the central nervous system and to highlight recent findings from our group showing its potential involvement in neurological illnesses including epilepsies, Parkinson's disease and Alzheimer's disease.
Assuntos
Polipeptídeo Inibidor Gástrico/metabolismo , Doenças do Sistema Nervoso/fisiopatologia , Receptores dos Hormônios Gastrointestinais/metabolismo , Animais , Sistema Nervoso Central/fisiologia , Sistema Nervoso Central/fisiopatologia , Sistemas de Liberação de Medicamentos , Humanos , Plasticidade Neuronal/fisiologiaRESUMO
Caffeine is one of the most used ergogenic aid for physical exercise and sports. However, its mechanism of action is still controversial. The adenosinergic hypothesis is promising due to the pharmacology of caffeine, a nonselective antagonist of adenosine A1 and A2A receptors. We now investigated A2AR as a possible ergogenic mechanism through pharmacological and genetic inactivation. Forty-two adult females (20.0 ± 0.2 g) and 40 male mice (23.9 ± 0.4 g) from a global and forebrain A2AR knockout (KO) colony ran an incremental exercise test with indirect calorimetry (VÌO2 and RER). We administered caffeine (15 mg/kg, i.p., nonselective) and SCH 58261 (1 mg/kg, i.p., selective A2AR antagonist) 15 min before the open field and exercise tests. We also evaluated the estrous cycle and infrared temperature immediately at the end of the exercise test. Caffeine and SCH 58621 were psychostimulant. Moreover, Caffeine and SCH 58621 were ergogenic, that is, they increased VÌO2max, running power, and critical power, showing that A2AR antagonism is ergogenic. Furthermore, the ergogenic effects of caffeine were abrogated in global and forebrain A2AR KO mice, showing that the antagonism of A2AR in forebrain neurons is responsible for the ergogenic action of caffeine. Furthermore, caffeine modified the exercising metabolism in an A2AR-dependent manner, and A2AR was paramount for exercise thermoregulation.
Assuntos
Antagonistas do Receptor A2 de Adenosina , Cafeína/farmacologia , Estimulantes do Sistema Nervoso Central , Substâncias para Melhoria do Desempenho , Condicionamento Físico Animal/fisiologia , Receptor A2A de Adenosina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Regulação da Temperatura Corporal/efeitos dos fármacos , Regulação da Temperatura Corporal/fisiologia , Cafeína/administração & dosagem , Ciclo Estral/efeitos dos fármacos , Feminino , Masculino , Camundongos , Camundongos Knockout , Neurônios/fisiologia , Prosencéfalo/citologia , Prosencéfalo/metabolismo , Pirimidinas/farmacologia , Triazóis/farmacologiaRESUMO
Regular exercise induces a wide range of redox system-associated molecular adaptive responses to the nervous system. The intermittent induction of reactive oxygen species (ROS) during acute exercise sessions and the related upregulation of antioxidant/repair and housekeeping systems are associated with improved physiological function. Exercise-induced proliferation and differentiation of neuronal stem cells are ROS dependent processes. The increased production of brain derived neurotrophic factor (BDNF) and the regulation by regular exercise are dependent upon redox sensitive pathways. ROS are causative and associative factors of neurodegenerative diseases and regular exercise provides significant neuroprotective effects against Alzheimer's disease, Parkinson's disease, and hypoxia/reperfusion related disorders. Regular exercise regulates redox homeostasis in the brain with complex multi-level molecular pathways.
Assuntos
Exercício Físico/fisiologia , Doenças Neurodegenerativas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Doença de Alzheimer/metabolismo , Animais , Antioxidantes/metabolismo , Encéfalo/metabolismo , Lesões Encefálicas Traumáticas/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Homeostase , Humanos , Hipóxia/metabolismo , Hipóxia-Isquemia Encefálica , Isquemia/metabolismo , Neuroproteção/fisiologia , Oxirredução , Doença de Parkinson/metabolismo , Acidente Vascular Cerebral/metabolismoRESUMO
This review highlighted resistance training as an important training type for the brain. Most studies that use physical exercise for the prevention or treatment of neurodegenerative diseases have focused on aerobic physical exercise, revealing different behavioral, biochemical, and molecular effects. However, recent studies have shown that resistance training can also significantly contribute to the prevention of neurodegenerative diseases as well as to the maintenance, development, and recovery of brain activities through specific neurochemical adaptations induced by the training. In this scenario we observed the results of several studies published in different journals in the last 20 years, focusing on the effects of resistance training on three main neurological aspects: Neuroprotective mechanisms, oxidative stress, and cognition. Systematic database searches of PubMed, Web of Science, Scopus, and Medline were performed to identify peer-reviewed studies from the 2000s. Combinations of keywords related to brain disease, aerobic/resistance, or strength physical exercise were used. Other variables were not addressed in this review but should be considered for a complete understanding of the effects of training in the brain.
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While chronic high-fat feeding has long been associated with the rising incidence of obesity/type 2 diabetes, recent evidence has established that it is also associated with deficits in hippocampus-dependent memory. In this regard, environmental enrichment (EE) is an animal housing technique composed of increased space, physical activity, and social interactions, which in turn increases sensory, cognitive, motor, and social stimulation. EE leads to improved cerebral health as defined by increased neurogenesis, enhanced learning and memory and resistance to external cerebral insults. In the present study, the impacts of environmental enrichment (EE) on Swiss mice fed a high-fat, cholesterol-enriched diet (HFECD; 20% fat and 1.5% cholesterol) were investigated. Here, we demonstrated that EE, when initiated 4 weeks after the beginning of HFECD in mice, prevents HFECD-induced spatial memory and object recognition impairment, which were tested in T-maze and object recognition tests. Although EE did not affect HFECD-induced weight gain or hypercholesterolaemia, it improved glucose tolerance. On the other hand, EE was unable to mitigate a decrease in brain-derived neurotrophic factor (BDNF) and IL-6 hippocampal levels induced by the HFECD. Overall, while our results reinforce the positive and neuroprotective effects of EE on cognition they do not support a role for EE in preventing the neurochemical changes induced by the HFECD. Based on clinical observations that nondiabetic individuals with mild forms of impaired glucose tolerance have a higher risk of cognitive impairments, one can speculate about the connection between the effects of EE on glucose intolerance and its effects on cognition.