Repeated binge-like ethanol administration during adolescence cause decreased C-Fos immunoreactivity in amygdala and arcuate nucleus in adult Sprague-Dawley rats / La administración repetida de etanol, tipo atracón, durante la adolescencia provoca descenso en la expresión de C-Fos en la amígdala y núcleo arqueado de ratas Sprague-Dawley adultas

Binge alcohol drinking during adolescence has been associated with neurotoxicity and increased risk for the development of alcohol use disorders. There is evidence that acute and chronic ethanol administration alters c-fos expression, an indirect index of cellular activity, in different brain regions in adult rats. We evaluate here if a binge-like pattern of ethanol exposure during adolescence has a relevant impact on basal and/or ethanol-stimulated regional c-fos activity during adulthood. For that aim, Sprague-Dawley rats PND 25 were saline pre-treated, (SP group) or binge-ethanol pre-treated (BEP group) for two­consecutive days, at 48-h intervals, over a 14-day period (PND 25 to PND 38). At adult stage (PND 63) and following 25 ethanol-free days, we evaluated c-fos immunoreactivity in response to saline or acute ethanol (1.5 or 3.0 g/kg) in the hypothalamus and amygdala. We found that acute ethanol administration dose-dependently increased c-fos activity in the the Paraventricular nucleus of the hypothalamus (PVN). Interestingly, binge-ethanol exposure during adolescence significantly reduced basal c-fos activity during adulthood in the Central nucleus of the amygdala (CeA) and the Arcuate nucleus of hypothalamus (Arc). We conclude that binge-like ethanol administration during adolescence causes long-term disturbances in basal neural activity in brain areas critically involved with ethanol consumption.

El consumo en atracón durante la adolescencia está asociado con neurotoxicidad y con el riesgo de desarrollar un trastorno en el uso de alcohol. Diversos estudios muestran que la administración aguda y crónica de alcohol en ratas adultas altera la expresión de c-fos, un marcador indirecto de actividad celular, en diferentes áreas cerebrales. Nosotros evaluamos si el patrón de consumo de alcohol en atracón durante la adolescencia tiene un impacto en la actividad basal de c-fos en esas regiones activadas por el alcohol. Utilizamos ratas Sprague-Dawley en su día post-natal 25 (PND25) tratadas con suero salino (grupo SP) o con etanol tipo atracón (grupo BEP) durante dos días consecutivos, en intervalos de 48 h, durante 14 días (PND25- PND38). En la edad adulta (PND63) y después de 25 días sin etanol, evaluamos la inmunorreactividad para c-fos en respuesta a una administración aguda de suero salino o etanol (1,5 ó 3,0 g/kg) en diferentes regiones cerebrales. La administración de alcohol incrementó de manera dosis-dependiente la actividad de c-fos en el núcleo paraventricular del hipotálamo. Además la exposición a etanol tipo atracón durante la adolescencia disminuyó la actividad basal de c-fos en la adultez en el núcleo central de la amígdala y en el núcleo arqueado del hipotálamo. Concluimos que el consumo de alcohol en atracón durante la adolescencia causa problemas a largo plazo en la actividad basal de regiones cerebrales implicadas en el consumo de alcohol.

A single high dose of chlorpyrifos reduces long-term basal c-fos expression in the rat arcuate hypothalamic nucleus / La administración de una dosis aguda de clorpirifós reduce a largo plazo la expresión basal de c-fos en el núcleo arqueado del hipotálamo

Chlorpyrifos (CPF) is an organophosphate compound used worldwide as a pesticide in agriculture that, after subcutaneous injection, keeps acetylcholinesterase (AChE) activity inhibited within an organism for months. Ample clinical and experimental evidence shows that CPF exposure induces relevant and persistent neurobehavioral deficits in humans and animals, even after one single episode/injection. Additionally, clinical and epidemiological studies evidence that a significant percentage (60%) of Gulf War veterans as well as agricultural workers suffering from acute OP intoxication may have developed intolerance to nicotine and ethanol-containing beverages. Consistent with it, administration of a single high dose of CPF to adult Wistar rats elicited long-lasting reduced voluntary ethanol drinking and increased sedation to ethanol without evidence of altered ethanol metabolism, which indicates that CPF-ethanol neurobiological interactions may exist. In this study, we explore whether CPF exposure induces significant disturbances in basal and/or ethanol-evoked neural activity in a set of cholinoceptive brain regions critically involved with neurobiological responses to ethanol. For this aim, brain regional c-fos expression in response to acute ethanol (1.5 or 3.0 g/kg, i.p.) or saline was assessed in adult male Wistar rats previously injected with either a single high dose of CPF (250 mg/kg, sc) or vehicle. We found that CPF administration reduces long-term basal, but not ethanol-evoked, c-fos expression in the arcuate hypothalamic nucleus. Because independent brain pathways may modulate acute responses to ethanol and voluntary ethanol consumption, we do not rule out the contribution of basal neural disturbances observed in the Arc to CPF-elicited ethanol avoidance.

El clorpirifós (CPF) es un compuesto organofosforado utilizado como plaguicida en todo el mundo. Después de ser inyectado de manera subcutánea, mantiene la actividad de la enzima acetilcolinesterasa (AChE) inhibida durante meses. Estudios clínicos y experimentales muestran que la exposición al CPF induce déficits neuroconductuales persistentes en seres humanos y animales, incluso después de un solo episodio/inyección. Además, estudios epidemiológicos evidencian que un porcentaje significativo (60%) de los veteranos de la Guerra del Golfo, así como los agricultores que sufren una intoxicación aguda por organofosforados, desarrollan intolerancia a la nicotina y las bebidas que contienen etanol. Datos experimentales mostraron que la administración de una sola dosis alta de CPF en ratas Wistar adultas provoca una reducción a largo plazo del consumo voluntario de etanol y un incremento en la sedación provocada por etanol sin evidencias de alteración del metabolismo de esta sustancia, lo que indica que pueden existir interacciones neurobiológicas entre CPF-etanol. En este estudio, se explora si la exposición a CPF induce alteraciones significativas en la actividad neuronal basal o evocada por el etanol en un conjunto de regiones colinoceptivas del cerebro involucradas en las respuestas neurobiológicas al etanol. Para ello, se evaluó la expresión de c-fos en respuesta a una dosis de etanol aguda (1.5 o 3.0 g/kg, ip) o solución salina en ratas Wistar macho adultas previamente inyectados con dosis aguda de CPF (250 mg/kg, sc) o un vehículo. Encontramos que la administración de CPF redujo la expresión basal de c-fos a largo plazo, pero no la evocada por el etanol en el núcleo arqueado del hipotalámo. Debido a que vías cerebrales independientes podrían modular las respuestas agudas al etanol y el consumo voluntario del mismo, no se descarta la contribución de las alteraciones neuronales basales observadas en el Arc en la evitación del consumo de etanol provocado por CPF.

Hypothalamic regulation of food intake and clinical therapeutic applications: [review] / Regulação hipotalâmica da ingestão alimentar e suas aplicações terapêuticas clínicas: [revisão]

Current estimates suggest that over 1 billion people are overweight and over 300 million people are obese. Weight gain is due to an imbalance between energy expenditure and dietary intake. This review discusses the hypothalamic control of appetite and highlights key developments in research that have furthered our understanding of the complex pathways involved. Nuclei within the hypothalamus integrate peripheral signals such as adiposity and caloric intake to regulate important pathways within the central nervous system controlling food intake and energy expenditure. Firmly established pathways involve the orexigenic NPY/AgRP and the anorexigenic POMC/CART neurons in the arcuate nucleus (ARC) of the hypothalamus. These project from the ARC to other important hypothalamic nuclei, including the paraventricular, dorsomedial, ventromedial and lateral hypothalamic nuclei. In addition there are many projections to and from the brainstem, cortical areas and reward pathways, which modulate food intake.

As estimativas atuais sugerem que mais de 1 bilhão de pessoas apresentam sobrepeso e 300 milhões são obesas. O ganho de peso representa um desequilíbrio entre o gasto energético e o consumo alimentar. Esta revisão discute o controle hipotalâmico do apetite e destaca os pontos-chave no desenvolvimento de pesquisas para ampliar o nosso entendimento dos complexos mecanismos envolvidos nesta regulação. Núcleos situados no hipotálamo integram uma série de sinais com o sistema nervoso central controlando a ingestão alimentar e o gasto energético. As vias mais estabelecidas envolvem os neurônios orexigênicos NPY/AgRP e os neurônios anorexigênicos POMC/CART no núcleo arqueado (ARC) do hipotálamo. Esses neurônios se projetam do ARC para outros importantes núcleos hipotalâmicos, tais quais: paraventricular, dorsomedial, ventromedial e lateral. Além disso, existem várias projeções que vão e vem do tronco cerebral, das áreas corticais e das vias de retroalimentação que modulam o consumo alimentar.

Glycogenolysis response to adrenergic agonists in the liver of rats treated with monosodium glutamate (MSG)

Administração de glutamato monossódico (MSG) em ratos neonatos causa lesão no núcleo arqueado (NA), seguido por uma síndrome de disfunção neuroendócrina caracterizada por obesidade e reduzida atividade simpática. O objetivo da presente investigação foi examinar a resposta da glicogenólise hepática a agonistas adrenérgico em ratos tratados com MSG. Ratos Wistar machos receberam injeções subcutâneas de MSG (4 mg g-1 de peso corporal) ou salina equimolar (controles) durante cinco dias após o nascimento. Noventa dias após o tratamento, os fígados de ratos-MSG ou controles foram perfundidos in situ com epinefrina e agonistas alfa- e beta-adrenérgico. Isoproterenol, fenilefrina e epinefrina aumentaram a glicogenólise em ratos-MSG, comparados aos controles (50 ± 2,8 Vs 17 ± 0,89 µmol min-1 g-1 de fígado, p < 0,0001; 64 ± 0,15 Vs 37 ± 0,39, p < 0,0001; 35 ± 2,48 Vs 27 ± 0,98, p < 0,05, respectivamente). Concluiu-se que a lesão do NA aumentou o catabolismo do glicogênio aos agonistas adrenérgicos, possivelmente devido à reduzida atividade do eixo simpático - medula adrenal.

Administration of MSG to neonate rats causes lesions in the arcuate nucleus (AN), followed by a syndrome of neuroendocrine dysfunction characterized by obesity and decreased sympathetic activity. The aim of the present investigation was to examine the responses of hepatic glycogenolysis to alpha and beta-adrenergic agonists in rats? treatment with MSG. Male Wistar rats received subcutaneous injections of MSG (4 mg g-1 body weight) or hyperosmotic saline (controls) during five days after birth. Ninety days after treatment, the livers of the MSG or controls rats were perfused in situ with epinephryne and alpha- and beta-adrenergic agonists. Epinephryne, Isoproterenol and phenylephrine increased glycogenolysis in the MSG-treated rats, compared to the controls (50 ± 2.8 Vs 17 ± 0.89 µmol min-1 g-1 of liver, p < 0.0001; 64 ± 0.15 Vs 37 ± 0.39, p < 0.0001; 35 ± 2.48 Vs 27 ± 0.98, p < 0.05, respectively). Results indicated that the lesion in the AN increased glycogen catabolism to adrenergic agonists, possibly, due to the reduced activity of the sympathetic-adrenal axis.