ABSTRACT
ABSTRACT Induction of long-term potentiation (LTP) increases the storage capacity of synapses in the hippocampal dentate gyrus (DG). Irisin is a myokine generated from FNDC5 (a gene precursor) during exercise. Although intra-cornu ammonis 1 administration of irisin fortifies LTP in mice with Alzheimer's disease, the effects of intra-DG injection of irisin on the LTP in rats remains to be elucidated in vivo. In this study, male Wistar rats were randomly divided into a control group (saline), irisin (0.5, 1, and 1.5 μg/rat), and dimethyl sulfoxide (DMSO). After treatment, the population spike (PS) amplitude and slope of excitatory postsynaptic potentials (EPSP) were measured in the DG of rats in vivo. Moreover, following completion of the experiments, the stimulating and recording sites in the hippocampus were confirmed histologically from brain sections. Furthermore, biochemical assays like malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidant status (TOS) were evaluated (the antioxidant markers were analyzed in the plasma). Our results suggest that all doses of irisin (0.5, 1, 1.5 μg/rat) caused an increase in the EPSP slope and PS amplitude when compared with the control group. In addition, the results obtained showed that irisin decreased TOS and MDA levels while increasing TAC levels as a marker of lipid peroxidation in plasma. The present report provides direct evidence that irisin affects the activity-dependent synaptic plasticity in the dentate gyrus.
RESUMO A indução de potenciação de longo prazo (LTP) aumenta a capacidade de armazenamento das sinapses no giro denteado (DG) do hipocampo. A irisina é uma miocina gerada a partir do FNDC5 (um precursor genético) durante o exercício. Embora a administração intra-Cornu Ammonis1 de irisina fortaleça a LTP em camundongos com doença de Alzheimer, os efeitos da injeção intra-denteada de irisina sobre a LTP em ratos ainda precisam ser elucidados in vivo. Neste estudo, ratos Wistar machos foram divididos aleatoriamente em um grupo controle (solução salina), irisina (0,5, 1 e 1,5 μg / rato) e dimetilsulfóxido (DMSO). Após o tratamento, a amplitude do pico populacional (PS) e a variação dos potenciais pós-sinápticos excitatórios (EPSP) foram medidos no DG de ratos in vivo. Além disso, após a conclusão das experiências, os locais de estimulação e registro no hipocampo foram confirmados histologicamente a partir de secções do cérebro. Adicionalmente, ensaios bioquímicos como malondialdeído (MDA), capacidade antioxidante total (TAC) e status oxidante total (TOS) foram avaliados (os marcadores antioxidantes foram analisados no plasma). Nossos resultados sugerem que todas as doses de irisina (0,5, 1, 1,5 μg / rato) causaram um aumento na variação da EPSP e na amplitude da PS quando comparadas com o grupo controle. Além disso, os resultados obtidos mostraram que a irisina diminuiu os níveis de TOS e MDA, enquanto aumentou os níveis de TAC como um marcador da peroxidação lipídica no plasma. O presente estudo fornece evidências diretas de que a irisina afeta a plasticidade sináptica dependente de atividade no DG.
Subject(s)
Animals , Male , Neuropeptides/administration & dosage , Fibronectins/administration & dosage , Long-Term Potentiation/drug effects , Dentate Gyrus/drug effects , Microinjections/methods , Reference Values , Time Factors , Lipid Peroxidation , Random Allocation , Reproducibility of Results , Rats, Wistar , Brain-Derived Neurotrophic Factor/analysis , Brain-Derived Neurotrophic Factor/drug effects , Excitatory Postsynaptic Potentials/drug effects , Malondialdehyde/blood , Antioxidants/analysisABSTRACT
The rat posterodorsal medial amygdala (MePD) links emotionally charged sensory stimuli to social behavior, and is part of the supramedullary control of the cardiovascular system. We studied the effects of microinjections of neuroactive peptides markedly found in the MePD, namely oxytocin (OT, 10 ng and 25 pg; n=6/group), somatostatin (SST, 1 and 0.05 μM; n=8 and 5, respectively), and angiotensin II (Ang II, 50 pmol and 50 fmol; n=7/group), on basal cardiovascular activity and on baroreflex- and chemoreflex-mediated responses in awake adult male rats. Power spectral and symbolic analyses were applied to pulse interval and systolic arterial pressure series to identify centrally mediated sympathetic/parasympathetic components in the heart rate variability (HRV) and arterial pressure variability (APV). No microinjected substance affected basal parameters. On the other hand, compared with the control data (saline, 0.3 µL; n=7), OT (10 ng) decreased mean AP (MAP50) after baroreflex stimulation and increased both the mean AP response after chemoreflex activation and the high-frequency component of the HRV. OT (25 pg) increased overall HRV but did not affect any parameter of the symbolic analysis. SST (1 μM) decreased MAP50, and SST (0.05 μM) enhanced the sympathovagal cardiac index. Both doses of SST increased HRV and its low-frequency component. Ang II (50 pmol) increased HRV and reduced the two unlike variations pattern of the symbolic analysis (P<0.05 in all cases). These results demonstrate neuropeptidergic actions in the MePD for both the increase in the range of the cardiovascular reflex responses and the involvement of the central sympathetic and parasympathetic systems on HRV and APV.
Subject(s)
Animals , Male , Arterial Pressure/drug effects , Baroreflex/drug effects , Corticomedial Nuclear Complex/drug effects , Heart Rate/drug effects , Neuropeptides/pharmacology , Wakefulness , Analysis of Variance , Angiotensin II/administration & dosage , Brain/anatomy & histology , Cardiovascular System/innervation , Corticomedial Nuclear Complex/metabolism , Hemodynamics/drug effects , Microinjections , Neuropeptides/administration & dosage , Oxytocin/administration & dosage , Parasympathetic Nervous System/drug effects , Rats, Wistar , Statistics, Nonparametric , Somatostatin/administration & dosage , Sympathetic Nervous System/drug effects , Vascular Access DevicesABSTRACT
In the forced swimming induced immobility test, neuropeptide FMRFamide (5-20 micrograms) administered via the intracerebroventricular (icv) route, prolonged immobilization period in rats. On the other hand, immunoneutralization of endogenous FMRFamide by its antiserum (1 microliter, icv) significantly reduced the duration of immobility. Intraperitoneal administration of amitriptyline (3 mg/kg), imipramine (5 mg/kg), fluoxetine (5 mg/kg) or amphetamine (0.5 mg/kg) attenuated FMRFamide-induced prolongation of immobility. Biochemical studies indicated that FMRFamide treatment had significant effects on rat brain monoamines. FMRFamide significantly lowered the brain levels of 5-hydroxytryptamine and norepinephrine in the doses that prolonged the immobility. These results that FMRFamide prolongs the duration of immobility, perhaps by modulating the release of neurotransmitters like 5-hydroxytryptamine and/or norepinephrine.
Subject(s)
Amino Acid Sequence , Animals , Antidepressive Agents/pharmacology , Brain/drug effects , FMRFamide , Immobilization , Injections, Intraventricular , Male , Molecular Sequence Data , Neuropeptides/administration & dosage , Norepinephrine/metabolism , Rats , Serotonin/metabolismABSTRACT
El amplio rango de actividades biologicas que tienen los NP llevan a pensar sobre su accion sobre ciertos sintomas del asma. Se han enfatizado la potencia espasmogenica, seguida de edema y participacion de los leucocitos. La capacidad de contraer el musculo liso sugiere un papel en la regulacion del tono de las vias aereas y conversion de la respuesta fisiologica en los sintomas del asma clinico. Su propiedad de inducir edema hace pensar en un posible rol en la presencia de hiper-reactividad bronquial.
Subject(s)
Humans , Male , Female , Asthma/drug therapy , Asthma/rehabilitation , Hypersensitivity/immunology , Antibodies/immunology , Neuropeptides/administration & dosage , Neuropeptides/metabolism , Autonomic Nervous System , Autonomic Nervous System/metabolismABSTRACT
The possible role of centrally administered tetrapeptide FMRFamide (Phe-Met-Arg-Phe-NH2) on gastric acid secretion in pylorus ligated rats was investigated. Intracerebroventricularly administered FMRFamide stimulated the gastric acid secretion in a dose-dependent manner. This stimulatory effect was abolished by vagotomy and atropine pretreatment. The presence of FMRFamide in rat brain and the ability of FMRFamide to stimulate gastric acid secretion suggest that FMRFamide plays a physiological role in brain modulation of gastric acid secretion.