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1.
Neurotherapeutics ; 15(2): 377-390, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29442286

RESUMO

The hypothalamus is involved in the regulation of homeostatic mechanisms and migraine-related trigeminal nociception and as such has been hypothesized to play a central role in the migraine syndrome from the earliest stages of the attack. The hypothalamus hosts many key neuropeptide systems that have been postulated to play a role in this pathophysiology. Such neuropeptides include but are not exclusive too orexins, oxytocin, neuropeptide Y, and pituitary adenylate cyclase activating protein, which will be the focus of this review. Each of these peptides has its own unique physiological role and as such many preclinical studies have been conducted targeting these peptide systems with evidence supporting their role in migraine pathophysiology. Preclinical studies have also begun to explore potential therapeutic compounds targeting these systems with some success in all cases. Clinical efficacy of dual orexin receptor antagonists and intranasal oxytocin have been tested; however, both have yet to demonstrate clinical effect. Despite this, there were limitations in these cases and strong arguments can be made for the further development of intranasal oxytocin for migraine prophylaxis. Regarding neuropeptide Y, work has yet to begun in a clinical setting, and clinical trials for pituitary adenylate cyclase activating protein are just beginning to be established with much optimism. Regardless, it is becoming increasingly clear the prominent role that the hypothalamus and its peptide systems have in migraine pathophysiology. Much work is required to better understand this system and the early stages of the attack to develop more targeted and effective therapies aimed at reducing attack susceptibility with the potential to prevent the attack all together.


Assuntos
Hipotálamo/metabolismo , Transtornos de Enxaqueca/metabolismo , Nociceptividade/fisiologia , Orexinas/uso terapêutico , Animais , Ensaios Clínicos como Assunto , Humanos , Transtornos de Enxaqueca/tratamento farmacológico , Neuropeptídeo Y/metabolismo , Neuropeptídeo Y/uso terapêutico , Ocitocina/metabolismo , Ocitocina/uso terapêutico , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/uso terapêutico , Resultado do Tratamento
2.
Peptides ; 31(12): 2193-9, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20863864

RESUMO

Neuropeptide Y (NPY) is a 36-amino-acid neuromodulator that is distributed throughout the central nervous system and has been implicated in a wide range of neurobiological responses including the integration of emotional behavior. The anxiolytic properties of NPY are modulated by NPY signaling in the hippocampus and in the central (CeA) and basolateral (BLA) nuclei of the amygdala. Recently, the neurotoxin saporin, when conjugated to NPY (NPY-SAP), was shown to selectively kill NPY receptor-expressing neurons and has been used as a tool to study the central NPY neurocircuitry involved with feeding behaviors. Here we determined if NPY-SAP can be used as a tool to study the central NPY neurocircuitry that modulates anxiety-like behaviors. BALB/cJ mice were given injection of either NPY-SAP or a control blank saporin (B-SAP) into the CeA or the basomedial hypothalamus (BMH) as a control injection site. The elevated zero maze test was used to assess anxiety-like behavior and NPY-SAP-induced lesions were verified using NPY Y1 receptor (Y1R) immunoreactivity (IR). Results showed that injection of NPY-SAP into the CeA site-specifically blunted Y1R IR in the CeA which was associated with a significant increase in anxiety-like behavior. Injection of NPY-SAP into the BMH, while locally blunting Y1R IR, promoted a compensatory increase of Y1R IR in the BLA and the CA3 region of the hippocampus which was associated with a significant reduction of anxiety-like behavior. The present set of experiments suggest that the NPY-SAP neurotoxin may be a useful tool for studying the NPY neurocircuitry that modulates anxiety-like behaviors.


Assuntos
Tonsila do Cerebelo/efeitos dos fármacos , Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Hipotálamo/efeitos dos fármacos , Neuropeptídeo Y/uso terapêutico , Proteínas Inativadoras de Ribossomos Tipo 1/uso terapêutico , Animais , Ansiolíticos/química , Imuno-Histoquímica , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Neuropeptídeo Y/química , Proteínas Inativadoras de Ribossomos Tipo 1/química , Saporinas
3.
Cell Mol Life Sci ; 60(2): 350-77, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12678499

RESUMO

The peptidic neuropeptide Y (NPY) has received great attention because it has been implicated in the regulation of several organ systems. In particular, NPY is involved in the regulatory loops that control food intake in the hypothalamus and appears also to be important for regulating the activity of neuroendocrine axes under poor metabolic conditions. Furthermore, NPY exerts vasoconstrictive action on the vasculature and potentiates the actions of many other vasoconstrictors. In addition, it was demonstrated to have trophic properties and could therefore contribute to cardiovascular remodeling. These various effects plus a number of others make NPY an attractive target for the potential treatment of human diseases, such as obesity, metabolic disorders, hypertension and heart failure.


Assuntos
Neuropeptídeo Y/metabolismo , Receptores de Neuropeptídeo Y/metabolismo , Animais , Anti-Hipertensivos/uso terapêutico , Estimulantes do Apetite/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Sistema Cardiovascular/metabolismo , Previsões , Humanos , Hipotálamo/metabolismo , Modelos Biológicos , Neuropeptídeo Y/uso terapêutico , Sistemas Neurossecretores/metabolismo , Processamento de Proteína Pós-Traducional , Receptores de Neuropeptídeo Y/genética , Transdução de Sinais
4.
Neuropsychopharmacology ; 26(5): 615-24, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-11927186

RESUMO

The present study was undertaken to investigate the possible antidepressant-like effects of neuropeptide Y (NPY) in the mouse forced swimming test, an animal model widely used for the screening of potential antidepressant drugs. In addition, experiments were performed, using agonists and selective antagonists, to assess the potential role of NPY Y(1) and Y(2) receptor subtypes in this model. Complementary studies were performed in an open field apparatus to rule out any changes in locomotor activity that might have interfered with the interpretation of data from the mouse forced swimming test. Intracerebroventricular injections (0.03 nmole-3 nmole) of NPY, [Leu(31)Pro(34)]PYY (Y(1) agonist), NPY(13-36) (Y(2) agonist), BIBP3226, BIBO3304 (Y(1) antagonists) and BIIE0246 (Y(2) antagonist) were performed 30 min prior to testing in the mouse forced swimming test and open field. NPY administration significantly reduced immobility time in a dose dependent manner (p <.01 vs. control group), as did [Leu(31)Pro(34)]PYY (p <.01 vs. control group) and BIIE0246 (p <.05 vs. control group). In contrast, BIBO3304, BIBP3226 and NPY(13-36) did not display any activity at the doses tested. However, pretreatment with BIBO3304 or BIBP3226 significantly blocked the anti-immobility effects of NPY. Data from the open field demonstrated that BIIE0246 increased horizontal ambulation at the dose found to be active in the forced swimming test. Taken together, our results demonstrate that NPY displays antidepressant-like activity in the mouse forced swimming test, and suggest that this activity is mediated by the NPY Y(1) receptor subtype.


Assuntos
Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Arginina/análogos & derivados , Atividade Motora/efeitos dos fármacos , Neuropeptídeo Y/fisiologia , Receptores de Neuropeptídeo Y/fisiologia , Natação , Animais , Arginina/farmacologia , Benzazepinas/farmacologia , Depressão/tratamento farmacológico , Depressão/fisiopatologia , Avaliação Pré-Clínica de Medicamentos/métodos , Imobilização/fisiologia , Masculino , Camundongos , Atividade Motora/fisiologia , Neuropeptídeo Y/farmacologia , Neuropeptídeo Y/uso terapêutico , Fragmentos de Peptídeos/farmacologia , Receptores de Neuropeptídeo Y/agonistas , Receptores de Neuropeptídeo Y/antagonistas & inibidores , Natação/fisiologia , Natação/psicologia
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