Cell proliferation and neuroblast differentiation in the dentate gyrus of high-fat diet-fed mice are increased after rosiglitazone treatment

In this study, we determined how rosiglitazone (RSG) differentially affected hippocampal neurogenesis in mice fed a low-fat diet (LFD) or high-fat diet (HFD; 60% fat). LFD and HFD were given to the mice for 8 weeks. Four weeks after initiating the LFD and HFD feeding, vehicle or RSG was administered orally once a day to both groups of mice. We measured cell proliferation and neuroblast differentiation in the subgranular zone of the dentate gyrus using Ki67 and doublecortin (DCX), respectively, as markers. In addition, we monitored the effects of RSG on the levels of DCX and brain-derived neurotrophic factor (BDNF) in hippocampal homogenates. At 8 weeks after the LFD feeding, the numbers of Ki67- and DCX-positive cells as well as hippocampal levels of DCX and BDNF were significantly decreased in the RSG-treated group compared to the vehicle-treated animals. In contrast, the numbers of Ki67- and DCX-positive cells along with hippocampal levels of DCX and BDNF in the HFD fed mice were significantly increased in the RSG-treated mice compared to the vehicle-treated group. Our data demonstrate that RSG can modulate the levels of BDNF, which could play a pivotal role in cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus.

Structurally conserved C-RFa revealed prolactin releasing activity in vitro and gene expression changes in pituitary of seasonally acclimatized carp

Here we show the cloning and characterization of a novel homolog of prepro C-RFa cDNA from Cyprinus carpió. The deduced preprohormone precursor of 115 amino acids leads to a mature bioactive peptide of 20 amino acids with identical sequence to other teleost C-RFa. Modeling of the mature C-RFa peptide highlighted significant similarity to homologous human PrRP20, specifically the conserved amphipathic system defined by the C-terminal alpha-helix. Clearly, the synthetic C-RFa peptide stimulated prolactin release from primary cultured fish pituitary cells. For the first time, significant variation was shown in C-RFa mRNA and protein levels in the hypothalamus and pituitary between summer- and winter-acclimatized carp. Furthermore, C-RFa protein distribution in carp central nervous tissue was visualized by immunodetection in fibers and cells in hypothalamus, olfactory tract, cerebellum and pituitary stalk. In conclusion, we demonstrated the structure conservation of C-RFa in teleosts and mammals and immunopositive cells and fibers for C-RFa in brain areas. Finally, the increase of C-RFa expression suggests the participation of this hypothalamic factor in the mechanism of modulation in PRL expression in carp.

Fast neutron irradiation deteriorates hippocampus-related memory ability in adult mice

Object recognition memory and contextual fear conditioning task performance in adult C57BL/6 mice exposed to cranial fast neutron irradiation (0.8 Gy) were examined to evaluate hippocampus-related behavioral dysfunction following acute exposure to relatively low doses of fast neutrons. In addition, hippocampal neurogenesis changes in adult murine brain after cranial irradiation were analyzed using the neurogenesis immunohistochemical markers Ki-67 and doublecortin (DCX). In the object recognition memory test and contextual fear conditioning, mice trained 1 and 7 days after irradiation displayed significant memory deficits compared to the sham-irradiated controls. The number of Ki-67- and DCX-positive cells decreased significantly 24 h post-irradiation. These results indicate that acute exposure of the adult mouse brain to a relatively low dose of fast neutrons interrupts hippocampal functions, including learning and memory, possibly by inhibiting neurogenesis.

Estradiol-induced hypophagia is associated with the differential mRNA expression of hypothalamic neuropeptides

Estradiol participates in the control of energy homeostasis, as demonstrated by an increase in food intake and in body weight gain after ovariectomy in rats. In the present study, female Wistar rats (200-230 g, N = 5-15 per group), with free access to chow, were individually housed in metabolic cages. We investigated food intake, body weight, plasma leptin levels, measured by specific radioimmunoassay, and the hypothalamic mRNA expression of orexigenic and anorexigenic neuropeptides, determined by real-time PCR, in ovariectomized rats with (OVX+E) and without (OVX) estradiol cypionate treatment (10 µg/kg body weight, sc, for 8 days). Hormonal and mRNA expression were determined at pre-feeding and 4 h after food intake. OVX+E rats showed lower food intake, less body weight gain and lower plasma leptin levels. In the OVX+E group, we also observed a reduction of neuropeptide Y (NPY), agouti-related protein (AgRP) and cocaine- and amphetamine-regulated transcript (CART) mRNA expression in the arcuate nucleus and a decrease in orexin A in the lateral hypothalamic area (LHA). There was an increase in leptin receptor (LepRb), melanocortin-4 receptor (MC4-R), CART, and mainly corticotropin-releasing hormone (CRH) mRNA in the paraventricular nucleus and LepRb and CART mRNA in the LHA. These data show that hypophagia induced by estradiol treatment is associated with reduced hypothalamic expression of orexigenic peptides such as NPY, AgRP and orexin A, and increased expression of the anorexigenic mediators MC4-R, LepRb and CRH. In conclusion, estradiol decreases food intake, and this effect seems to be mediated by peripheral factors such as leptin and the differential mRNA expression of neuropeptides in the hypothalamus.

Narcolepsy: Clinical features, co-morbidities & treatment.

Narcolepsy is a neurologic illness that typically begins in the second and third decades of life. It is chronic in nature and negatively impacts the quality of life of affected patients. The classic presentation is a tetrad of excessive daytime sleepiness, cataplexy, sleep paralysis, and hypnagogic hallucinations. The exact cause remains unknown, but there is significant evidence that hypocretin deficiency plays an integral role. Some primary conditions that result in secondary narcolepsy include traumatic brain injury, congenital disorders, tumours, and strokes. Some medical and psychiatric disorders share characteristics of narcolepsy, at times leading to diagnostic inaccuracy. Other sleep disorders are commonly co-morbid. Diagnosis relies on patient history and objective data gathered from polysomnography and multiple sleep latency testing. Treatment focuses on symptom relief through medication, education, and behavioural modification. Both classic pharmacological treatments as well as newer options have significant problems, especially because of side effects and abuse potential. Novel modalities are being examined to expand options for treatment.

Rhodnius prolixus Malpighian tubules and control of diuresis by neurohormones

Rhodnius prolixus Malpighian tubules (MTs) are a good model for fluid and ion secretion studies in view of the dramatic postprandial diuresis, which follows its massive blood meals. Ingestion of a blood meal equals to 10-12 times their initial body mass, leads to rapid activation of high output by excretory system, which eliminates 40-50 percent of the fluid mass. Secretion of ions and water is stimulated 1000-fold by serotonin and diuretic hormone. These hormones cooperate synergistically to activate adenylate cyclase activity from MTs cells, which increase the level of intracellular cAMP. The anti-diuretic hormones have also an important role in the fluid maintenance of Rhodnius prolixus. Several hours after insect feeding occurs a reduction in urine flow, that has been thought to result from a decreased diuretic hormone release or from a novel mechanism of anti-diuresis involving insect cardioacceleratory peptide 2b (CAP2b) and cyclic GMP. In this article it is discussed how the hormone regulation of fluid transport is done in Rhodnius prolixus MTs.

Os túbulos de Malpighi (TMs) de Rhodnius prolixus são reconhecidos por serem excelentes modelos para o estudo da secreção de fluidos e íons devido a grande diurese que ocorre quando esses animais se alimentam de sangue. O inseto, após alimentação, pode aumentar seu peso corporal inicial em até 10-12 vezes, o que leva a rápida ativação do sistema excretor, que elimina 40-50 por cento do fluido corporal. A secreção de íons e água é estimulada 1000 vezes pela serotonina e pelos hormônios diuréticos. Esses hormônios agem sinergicamente ativando a adenil ciclase das células dos TMs, aumentando os níveis intracelulares de AMPc. Os hormônios anti-diuréticos também têm um importante papel na manutenção dos fluídos corporais do Rhodnius prolixus. Várias horas após a alimentação do inseto ocorre uma redução do fluxo urinário, o que foi sugerido ser decorrente da diminuição da liberação dos hormônios diuréticos ou da anti-diurese envolvendo o peptídeo cardioaceleratório 2b (CAP2b) e o GMPc. Neste artigo é discutida a regulação hormonal do transporte de fluido nos MTs de Rhodnius prolixus.

Changes in orexin-A and neuropeptide Y expression in the hypothalamus of the fasted and high-fat diet fed rats

This study was aimed to investigate the changes of orexin-A (OXA) and neuropeptide Y (NPY) expression in the hypothalamus of the fasted and high-fat diet fed rats. For the experiments, the male Sprague-Dawley (SD) rats were used as the model of high-fat diet-induced obesity. The mean loss of body weight (MLBW) did not show the linear pattern during the fasting; from 24 h to 84 h of fastings, the MLBW was not significantly changed. The numbers of OXA-immunoreactive (IR) neurons were decreased at 84 h of fasting compared with those in other five fasting subgroups. The NPY immunoreactivities in the arcuate nucleus (ARC) and the suprachiasmatic nucleus (SCN) observed at 84 h of fasting were higher than that observed at 24 h of fasting. The number of OXA-IR neurons of the LHA (lateral hypothalamic area) in the high-fat (HF) diet fed group was more increased than that of the same area in the normal-fat (NF) diet fed group. The NPY immunoreactivities of the ARC and the SCN were higher in HF group than those observed in the same areas of NF group. Based on these results, it is noteworthy that the decrease of the body weight during the fast was not proportionate to the time-course, implicating a possible adaptation of the body for survival against starvation. The HF diet might activate the OXA and the NPY in the LHA to enhance food intake.

La interrupción temprana del vínculo social altera la organización citoarquitectónica y expresión de neuropéptidos en la corteza prefrontal / Early disruption of social attachment alters the cytoarchitectonic organization and neuropeptide expression in the prefrontal cortex

En el presente trabajo se evalúa el efecto que produce el entorno social sobre la maduración neuronal y la expresión del péptido intestinal vasoactivo (VIP) en ratas postlactantes. Se emplearon técnicas de Golgi-Cox-Sholl e inmunocitoquímicas para evaluar el patrón de ramificación dendrítica y la expresión de VIP en animales criados en un medio social aislado (SA) versus uno social habitual (SH). Las ratas del grupo SA presentaron un menor porcentaje de dendritas basales asociado a un incremento en la expresión de VIP respecto de los animales SH. Estas alteraciones neuronales no fueron recuperadas a pesar de restituirles su entorno social durante 30 días. Los animales SA mostraron además un deterioro significativo de la conducta exploratoria. Estos hallazgos conjuntamente con antecedentes clínicos previos sugieren que el ambiente social temprano puede ocacionar cambios morfofuncionales notables en la corteza prefrontal

Neuropeptide control of the cardiovascular system in fish and reptiles

Accumulating evidence shows the involvement of neuropeptides in cardiovascular control in mammals as well as non-mammalian species. Our own immunohistochemical studies indicate a sparse innervation only in cyclostomes, holostean fish and lungfish, a more extensive variation and distribution in elasmobranchs and teleosts, and a rich and varied innervation of the cardiovascular system in crocodiles and lizards. Vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), gastrin releasing peptide (GRP) and tachykinins are present in most vertebrate groups. VIP is vasodilatory in the Atlantic cod (Gadus morhua) as in most mammalian species, but increases gut vascular resistance in the spiny dogfish (Squalus acanthias). NPY potentiates the effect of noradrenaline on skate (Raja rhina) coronary vessels, suggesting an interaction between adrenergic mechanisms and NPY early in evolution, but studies in the spiny dogfish and the crocodile also demonstrate different mechanisms for the action of NPY and adrenaline in some species. Bombesin/GRP increases flow to the gut in the spiny dogfish by an increase in somatic vascular resistance, while visceral resistance remains unchanged. In the caiman (Caiman crocodylus crocodylus) bombesin causes a shunting of blood from the lung to the gut. Substance P and other tachykinins in general increase flow to the gut, and on some occasions also increase somatic blood flow. Flow in the anastomosis of the crocodile (Crocodylus porosus) gut is increased by substance P. The results presented here are a review of several published and unpublished studies.

A new fluorometric assay for neutral endopeptidase (EC 3.4.24.11)

An intramolecularly quenched fluorogenic peptide structurally related to Leu-enkephalin, Abz-GGdFLRRV-EDDnp, was selectively hydrolyzed at the R-V bond by neutral endopeptidase (NEP, enkephalinase, neprilysin, EC 3.4.24.11) with kinetic parameters (Km = 3 µM,Kcat = 127 / min and Kcat / Km = 42 / min µM) similar to those of Leu-enkephalin. The specificity of the assay for NEP was demostrated by incubating Abz-GGdFLRRV-EDDnp with a kidney homogenate and with crude membrane preparations of brain and lung. For all three homogenates the complementary fragments Abz-GGdFLRRnp accounted for more than 95 percent of the products wich were totally inhibited by 1 µM thiorphan, a highly specific NEP inhibitor. A continuous fluorometric assay for only 5 min was sufficient to quantify the NEP activity with a minimum sensitivity of 5 ng of purified NEP or the equivalent enzymatic activity in crude tissue preparations.

Asma bronquial II respuesta de anticuerpos (IgE) y sistema nervioso autonomo (neuropeptidos) / Bronchial asthma II; response of antibodies (IgE) and central nervous sistem (neuropeptides)

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.

Fatores psicogênicos em psoríase, estudo caso-controle seccional cruzado de 41 psoriáticos e 88 controles / The contributing evidences of psychological aspects in psoriasis

A psoríase é uma doença de múltiplos aspectos etiopatogênicos näo definitivamente estabelecidos. Sua relaçäo com fatores emocionais é encontrada na maioria das pesquisas sem, contudo, determinar se esta correlaçäo se daria no desencadeamento da doença, em seu curso evolutívo, ou em ambos. Aqui, säo revistas as principais publicaçöes sobre fatores psicológicos e psoríase. Ressalta-se, como resultante da análise crítica desta bibliografia, a necessidade de novas e bem conduzidas investigaçöes prospectivas para a averiguaçäo da possibilidade de atuaçäo de fatores psíquicos e psicossociais no desencademento e/ou curso da doença. Neste estudo foram analizadas 41 fichas de doentes de psoríase e 88 fichas de pacientes de diferentes dermatoses e escolhidas de forma aleatória em fichário do consultório de uma das autoras. Os dados foram submetidos às análises estatísticas e mostraram que o grupo de doentes de psoríase avaliado, tem queixas de fundo emocional significativamente elevadas em relaçäo ao grupo controle. Este aumento ocorre, tanto no início como no curso da psoríase