RESUMO
KEY POINTS: Perioral tactile signals are transmitted via the infraorbital nerve (ION) to trigeminal nuclei. Each cerebellar Purkinje cell (PC) receives this signal as complex spikes (CSs) via a climbing fibre (CF) emerging from the inferior olive (IO). The anatomical pathway from trigeminal nuclei to the IO is not clearly identified. In the present study, we examined candidate anatomical pathways for perioral sensory signalling by analysing CSs recorded from PCs in male mice by single unit recording. CS generation by ION stimulation was inhibited by injection of a GABAA receptor agonist, muscimol, into the contralateral mesodiencephalic junction, which is referred to as the area parafascicularis prerubralis (PfPr). The number of CSs evoked by mechanical whisker stimulation was also decreased by contralateral PfPr inhibition. These results suggest the existence of a sensory signalling pathway to the IO via the PfPr in mice. ABSTRACT: Perioral tactile signals are transmitted via the infraorbital nerve (ION) to trigeminal nuclei. Each cerebellar Purkinje cell receives this signal as complex spikes (CSs) via a climbing fibre emerging from the inferior olive (IO). However, the anatomical pathway from the trigeminal nuclei to the IO is not clearly identified. In the present study, we recorded CSs from Purkinje cells in male mice by single unit recording, and examined the signal transduction pathway. CSs were evoked by electrical stimulation of the ipsilateral or contralateral ION with a latency of 20-70 ms. CS generation by ipsilateral ION stimulation was inhibited by injection of a GABAA receptor agonist, muscimol, into the contralateral mesodiencephalic junction, ranging from around the fasciculus retroflexus to the interstitial nucleus of Cajal, which is referred to as the area parafascicularis prerubralis (PfPr). CSs evoked by contralateral ION stimulation were also suppressed by muscimol injection into the PfPr, although the effective area was more restricted. Furthermore, CSs evoked by mechanical stimulation around the whisker region were suppressed by PfPr inhibition. We also found that the primary motor cortex plays a role to suppress this signalling pathway. These results indicate the existence of an anatomical pathway for conducting perioral sensory signals to the IO via the PfPr.
Assuntos
Cerebelo/fisiologia , Diencéfalo/fisiologia , Mesencéfalo/fisiologia , Boca/fisiologia , Núcleo Olivar/fisiologia , Células de Purkinje/fisiologia , Células Receptoras Sensoriais/fisiologia , Animais , Células Cultivadas , Cerebelo/citologia , Cerebelo/efeitos dos fármacos , Diencéfalo/citologia , Diencéfalo/efeitos dos fármacos , Agonistas de Receptores de GABA-A/farmacologia , Masculino , Mesencéfalo/citologia , Mesencéfalo/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Boca/citologia , Boca/efeitos dos fármacos , Muscimol/farmacologia , Núcleo Olivar/citologia , Núcleo Olivar/efeitos dos fármacos , Células de Purkinje/citologia , Células de Purkinje/efeitos dos fármacos , Receptores de GABA-A/química , Células Receptoras Sensoriais/citologia , Células Receptoras Sensoriais/efeitos dos fármacosRESUMO
Most wrasses are protogynous species that swim to feed, reproduce during the daytime, and bury themselves under the sandy bottom at night. In temperate and subtropical wrasses, low temperature influences emergence from the sandy bottom in the morning, and induces a hibernation-like state in winter. We cloned and characterized the prohormone complementary DNAs (cDNAs) of arginine vasotocin (AVT) and isotocin (IT) in a temperate wrasse (Halichoeres tenuispinis) and examined the effects of day/night and temperature on their expression in the diencephalon, because these neurohypophysial peptides are related to the sex behavior of wrasses. The full-length cDNAs of pro-AVT and pro-IT were 938 base pairs (154 amino acids) and 759 base pairs (156 amino acids) in length, respectively. Both pro-peptides contained a signal sequence followed by the respective hormones and neurophysin connected by a Gly-Lys-Arg bridge. Reverse-transcription polymerase chain reaction (RT-PCR) revealed that pro-AVT mRNA expression was specifically observed in the diencephalon, whereas pro-IT mRNA expression was seen in the whole brain. Quantitative RT-PCR revealed that the mRNA abundance of pro-AVT and pro-IT was higher at midday (zeitgeber time 6; ZT6) than at midnight (ZT18) under 12 h light and 12 h darkness (LD 12:12) conditions, but not under constant light. Intraperitoneal injection of melatonin decreased the mRNA abundance of pro-AVT, but not of pro-IT. When fish were reared under LD 12:12 conditions at 25, 20, and 15 °C, day high and night low mRNA expressions of pro-AVT and pro-IT were maintained. A field survey revealed seasonal variation in the number of swimming fish at observatory sites; many fish emerged from the sandy bottom in summer, but not in winter, suggesting a hibernation-like state under the sandy bottom under low temperature conditions. We conclude that the day-night fluctuation of pro-AVT and pro-IT mRNA abundance in the brain is not affected by temperature and repeated under the sandy bottom in winter.
Assuntos
Diencéfalo/metabolismo , Peixes/genética , Melatonina/farmacologia , Ocitocina/análogos & derivados , Temperatura , Vasotocina/genética , Animais , Diencéfalo/efeitos dos fármacos , Ocitocina/genética , Periodicidade , RNA Mensageiro/metabolismoRESUMO
BACKGROUND: Antioxidants such as the green tea polyphenol epigallocatechin gallate (EGCG) are neuroprotective under many conditions in mature nervous systems; however, their impact has rarely been explored in developing nervous systems, in which a critical step is the formation of connections between neurons. Axons emerge from newly formed neurons and are led by a dynamic structure found at their tip called a growth cone. Here we explore the impact of EGCG on the development of retinal ganglion cell (RGC) axons, which connect the eye to the brain. RESULTS: EGCG acts directly on RGC axons to increase the number of growth cone filopodia, fingerlike projections that respond to extrinsic signals, in vitro and in vivo. Furthermore, EGCG exposure leads to a dramatic defect in the guided growth of RGC axons where the axons fail to make a key turn in the mid-diencephalon required to reach their target. Intriguingly, at guidance points where RGCs do not show a change in direction, EGCG has no influence on RGC axon behavior. CONCLUSIONS: We propose that EGCG stabilizes filopodia and prevents normal filopodial dynamics required for axons to change their direction of outgrowth at guidance decision points. Developmental Dynamics 245:667-677, 2016. © 2016 Wiley Periodicals, Inc.
Assuntos
Axônios/efeitos dos fármacos , Axônios/metabolismo , Catequina/análogos & derivados , Cones de Crescimento/efeitos dos fármacos , Pseudópodes/efeitos dos fármacos , Células Ganglionares da Retina/citologia , Células Ganglionares da Retina/efeitos dos fármacos , Animais , Orientação de Axônios/efeitos dos fármacos , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Catequina/farmacologia , Gonadotropina Coriônica/farmacologia , Diencéfalo/citologia , Diencéfalo/efeitos dos fármacos , Embrião não Mamífero/citologia , Embrião não Mamífero/efeitos dos fármacos , Feminino , Humanos , Hibridização In Situ , Neurogênese/efeitos dos fármacos , Retina/citologia , Retina/efeitos dos fármacos , XenopusRESUMO
Histone deacetylases (HDACs) are key epigenetic enzymes and emerging drug targets in cancer and neurodegeneration. Pan-HDAC inhibitors provided neuroprotection in Parkinson's Disease (PD) models, however, the HDAC isoforms with highest neuroprotective potential remain unknown. Zebrafish larvae (powerful pharmacological testing tools bridging cellular and in vivo studies) have thus far been used in PD modelling with limited phenotypic characterization. Here we characterize the behavioural and metabolic phenotypes of a zebrafish PD model induced with MPP(+), assess the feasibility of targeting zebrafish HDAC1 and HDAC6 isoforms, and test the in vivo effects of their selective inhibitors MS-275 and tubastatin A, respectively. MPP(+) induced a concentration-dependent decrease in metabolic activity and sensorimotor reflexes, and induced locomotor impairments rescuable by the dopaminergic agonist apomorphine. Zebrafish HDAC1 and HDAC6 isoforms show high sequence identity with mammalian homologues at the deacetylase active sites, and pharmacological inhibition increased acetylation of their respective histone and tubulin targets. MS-275 and tubastatin rescued the MPP(+)-induced decrease in diencephalic tyrosine hydroxylase immunofluorescence and in whole-larvae metabolic activity, without modifying mitochondrial complex activity or biogenesis. MS-275 or tubastatin alone modulated spontaneous locomotion. When combined with MPP(+), however, neither MS-275 nor tubastatin rescued locomotor impairments, although tubastatin did ameliorate the head-reflex impairment. This study demonstrates the feasibility of pharmacologically targeting the zebrafish HDAC1 and HDAC6 isoforms, and indicates that their inhibition can rescue cellular metabolism in a PD model. Absence of improvement in locomotion, however, suggests that monotherapy with either HDAC1 or HDAC6 inhibitors is unlikely to provide strong benefits in PD. This study highlights parameters dependent on the integrity of zebrafish neuronal circuits as a valuable complement to cell-based studies. Also, the demonstrated feasibility of pharmacologically targeting HDAC1 and HDAC6 in this organism paves the way for future studies investigating HDAC inhibitors in other diseases modelled in zebrafish.
Assuntos
Benzamidas/farmacologia , Histona Desacetilase 1/antagonistas & inibidores , Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Indóis/farmacologia , Doença de Parkinson Secundária , Piridinas/farmacologia , Proteínas de Peixe-Zebra/antagonistas & inibidores , 1-Metil-4-fenilpiridínio , Animais , Comportamento Animal/efeitos dos fármacos , Diencéfalo/efeitos dos fármacos , Diencéfalo/metabolismo , Modelos Animais de Doenças , Histona Desacetilase 1/genética , Desacetilase 6 de Histona , Histona Desacetilases/genética , Larva , Locomoção/efeitos dos fármacos , Neurotoxinas , Oxazinas/metabolismo , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/tratamento farmacológico , Doença de Parkinson Secundária/metabolismo , Doença de Parkinson Secundária/fisiopatologia , RNA Mensageiro/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo , Xantenos/metabolismo , Peixe-Zebra , Proteínas de Peixe-Zebra/genéticaRESUMO
In sheep as in rat, it has been highly suggested that neuronal histamine (HA) participates to the estradiol (E2)-induced GnRH and LH surges, through H1 receptor. With the aim of determining if E2 could act directly on HA neurons, we examined here whether HA neurons express estrogen receptor alpha (ERα) in the ewe diencephalon during the breeding season. We first produced a specific polyclonal antibody directed against recombinant ovine histidine decarboxylase (oHDC), the HA synthesizing enzyme. Using both this anti-oHDC antibody and an anti-ERα monoclonal antibody in double label immunohistochemistry, we showed that HA neurons do not express ERα in diencephalon of ewes with different hormonal status. This result diverges from those obtained in rat, in which around three quarters of HA neurons express ERα in their nucleus. This discrepancy between these two mammal species may reflect difference in their neuronal network.
Assuntos
Cruzamento , Diencéfalo/metabolismo , Receptor alfa de Estrogênio/metabolismo , Histamina/metabolismo , Neurônios/metabolismo , Estações do Ano , Ovinos/metabolismo , Animais , Anticorpos/metabolismo , Especificidade de Anticorpos/imunologia , Diencéfalo/citologia , Diencéfalo/efeitos dos fármacos , Diencéfalo/enzimologia , Eletroforese em Gel de Poliacrilamida , Estradiol/farmacologia , Feminino , Histidina Descarboxilase/imunologia , Imuno-Histoquímica , Masculino , Neurônios/efeitos dos fármacos , Ratos , Proteínas Recombinantes/isolamento & purificaçãoRESUMO
The first studies that identified leptin and its receptor (LepR) in mammals were based on mutant animals that displayed dramatic changes in body-weight and regulation of energy homeostasis. Subsequent studies have shown that a deficiency of leptin or LepR in homoeothermic mammals results in hyperphagia, obesity, infertility and a number of other abnormalities. The physiological roles of leptin-mediated signaling in ectothermic teleosts are still being explored. Here, we produced medaka with homozygous LepR gene mutation using the targeting induced local lesions in a genome method. This knockout mutant had a point mutation of cysteine for stop codon at the 357th amino acid just before the leptin-binding domain. The evidence for loss of function of leptin-mediated signaling in the mutant is based on a lack of response to feeding in the expression of key appetite-related neuropeptides in the diencephalon. The mutant lepr−/− medaka expressed constant up-regulated levels of mRNA for the orexigenic neuropeptide Ya and agouti-related protein and a suppressed level of anorexigenic proopiomelanocortin 1 in the diencephalon independent of feeding, which suggests that the mutant did not possess functional LepR. Phenotypes of the LepR-mutant medaka were analyzed in order to understand the effects on food intake, growth, and fat accumulation in the tissues. The food intake of the mutant medaka was higher in post-juveniles and adult stages than that of wild-type (WT) fish. The hyperphagia led to a high growth rate at the post-juvenile stage, but did not to significant alterations in final adult body size. There was no additional deposition of fat in the liver and muscle in the post-juvenile and adult mutants, or in the blood plasma in the adult mutant. However, adult LepR mutants possessed large deposits of visceral fat, unlike in the WT fish, in which there were none. Our analysis confirms that LepR in medaka exert a powerful influence on the control on food intake. Further analyses using the mutant will contribute to a better understanding of the role of leptin in fish. This is the first study to produce fish with leptin receptor deficiency.
Assuntos
Animais Geneticamente Modificados/crescimento & desenvolvimento , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Técnicas de Inativação de Genes , Gordura Intra-Abdominal/efeitos dos fármacos , Neuropeptídeos/farmacologia , Receptores para Leptina/fisiologia , Proteína Relacionada com Agouti/metabolismo , Animais , Animais Geneticamente Modificados/metabolismo , Apetite/efeitos dos fármacos , Apetite/fisiologia , Diencéfalo/efeitos dos fármacos , Diencéfalo/metabolismo , Ingestão de Alimentos/efeitos dos fármacos , Hiperfagia/genética , Hiperfagia/patologia , Leptina/metabolismo , Mutação/genética , Obesidade/metabolismo , Oryzias/genética , Oryzias/crescimento & desenvolvimento , Oryzias/metabolismo , Regulação para CimaRESUMO
The effects of original Russian preparations, derivatives of 3-hydroxypyridine and succinic acid (emoxipin, reamberin, mexidol), on the cellular composition of the cerebrocortical and diencephalic structures were studied and correlations of shifts in the cellular composition with changes in the severity of hyperglycemia in rats with alloxan diabetes were analyzed. The efficiency of 3-hydroxypyridine and succinic acid derivatives was evaluated in comparison with α-lipoic acid. Seven injections of the optimal doses of all the studied drugs prevented the neuron loss in layers I-III of the primary somatosensory cortex. In addition, emoxipin, reamberin, and α-lipoic acid prevented astrocyte loss in the neocortical surface layers and of neurons in the hypothalamic paraventricular nucleus. Reamberin limited microglial infiltration of the hippocampal field CA1. Injection of α-lipoic acid augmented the increase in astrocyte count in the paraventricular nucleus and potentiated the reduction of tigroid granularity of CA1 field neurons. Emoxipin and mexidol caused an increase in the counts of neurons and oligodendrocytes in CA1 field. By contrast, reamberin and α-lipoic acid reduced the counts of neurons and oligodendrocytes, respectively, in this hippocampal zone. More favorable effects of emoxipin and mexidol vs. reamberin and α-lipoic acid on the cellular composition of the hippocampus of rats with alloxan diabetes were explained by more effective correction of hyperglycemia under the effect of 3-hydroxypyridine derivatives.
Assuntos
Córtex Cerebral/efeitos dos fármacos , Diabetes Mellitus Experimental/patologia , Hipocampo/efeitos dos fármacos , Meglumina/análogos & derivados , Fármacos Neuroprotetores/farmacologia , Picolinas/farmacologia , Succinatos/farmacologia , Aloxano , Animais , Astrócitos/efeitos dos fármacos , Córtex Cerebral/patologia , Diencéfalo/efeitos dos fármacos , Diencéfalo/patologia , Feminino , Hipocampo/patologia , Hiperglicemia/tratamento farmacológico , Masculino , Meglumina/farmacologia , Neurônios/efeitos dos fármacos , Oligodendroglia/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/patologia , Ratos , Ácido Tióctico/farmacologiaRESUMO
Chronic nicotine produces up-regulation of α4ß2* nicotinic acetylcholine receptors (nAChRs) (* denotes that an additional subunit may be part of the receptor). However, the extent of up-regulation to persistent ligand exposure varies across brain regions. The aim of this work was to study the cellular distribution and function of nAChRs after chronic nicotine treatment in primary cultures of mouse brain neurons. Initially, high-affinity [(125)I]epibatidine binding to cell membrane homogenates from primary neuronal cultures obtained from diencephalon and hippocampus of C57BL/6J mouse embryos (embryonic days 16-18) was measured. An increase in α4ß2*-nAChR binding sites was observed in hippocampus, but not in diencephalon, after 24 h of treatment with 1 µM nicotine. However, a nicotine dose-dependent up-regulation of approximately 3.5- and 0.4-fold in hippocampus and diencephalon, respectively, was found after 96 h of nicotine treatment. A significant fraction of total [(125)I]epibatidine binding sites in both hippocampus (45%) and diencephalon (65%) was located on the cell surface. Chronic nicotine (96 h) up-regulated both intracellular and surface binding in both brain regions without changing the proportion of those binding sites compared with control neurons. The increase in surface binding was not accompanied by an increase in nicotine-stimulated Ca(2+) influx, suggesting persistent desensitization or inactivation of receptors at the plasma membrane occurred. Given the differences observed between hippocampus and diencephalon neurons exposed to nicotine, multiple mechanisms may play a role in the regulation of nAChR expression and function.
Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Nicotina/farmacologia , Piridinas/metabolismo , Receptores Nicotínicos/metabolismo , Alquilação/efeitos dos fármacos , Animais , Sítios de Ligação , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Cálcio/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Células Cultivadas , Diencéfalo/efeitos dos fármacos , Diencéfalo/metabolismo , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Radioisótopos do Iodo/análise , Camundongos , Camundongos Endogâmicos C57BL , Piridinas/farmacologia , Regulação para Cima/efeitos dos fármacosRESUMO
BACKGROUND: Higher aluminum (Al) content in infant formula and its effects on neonatal brain development are a cause for concern. This study aimed to evaluate the distribution and concentration of Al in neonatal rat brain following Al treatment, and oxidative stress in brain tissues induced by Al overload. METHODS: Postnatal day 3 (PND 3) rat pups (n =46) received intraperitoneal injection of aluminum chloride (AlCl3), at dosages of 0, 7, and 35 mg/kg body wt (control, low Al (LA), and high Al (HA), respectively), over 14 d. RESULTS: Aluminum concentrations were significantly higher in the hippocampus (751.0 ± 225.8 ng/g v.s. 294.9 ± 180.8 ng/g; p < 0.05), diencephalon (79.6 ± 20.7 ng/g v.s. 20.4 ± 9.6 ng/g; p < 0.05), and cerebellum (144.8 ± 36.2 ng/g v.s. 83.1 ± 15.2 ng/g; p < 0.05) in the HA group compared to the control. The hippocampus, diencephalon, cerebellum, and brain stem of HA animals displayed significantly higher levels of lipid peroxidative products (TBARS) than the same regions in the controls. However, the average superoxide dismutase (SOD) activities in the cerebral cortex, hippocampus, cerebellum, and brain stem were lower in the HA group compared to the control. The HA animals demonstrated increased catalase activity in the diencephalon, and increased glutathione peroxidase (GPx) activity in the cerebral cortex, hippocampus, cerebellum, and brain stem, compared to controls. CONCLUSION: Aluminum overload increases oxidative stress (H2O2) in the hippocampus, diencephalon, cerebellum, and brain stem in neonatal rats.
Assuntos
Alumínio/administração & dosagem , Desenvolvimento Embrionário/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Alumínio/metabolismo , Animais , Mapeamento Encefálico , Tronco Encefálico/efeitos dos fármacos , Tronco Encefálico/metabolismo , Cerebelo/efeitos dos fármacos , Cerebelo/metabolismo , Diencéfalo/efeitos dos fármacos , Diencéfalo/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Ratos , Distribuição TecidualRESUMO
Fipronil (FIP) is a highly effective insecticide that has been used in agriculture and veterinary medicine. Its neurotoxic effect to insects and to non-target organisms, after nonintentional exposure, was reported. Many studies were conducted to evaluate FIP effects on mammals. However, slight is known about its effect on the brain stem and diencephalon. The current study was designed to investigate the ability of FIP to induce oxidative stress as a molecular mechanism of FIP neurotoxicity that resulted in apoptosis and neural tissue reactivity in these regions. Ten adult male rats received 10 mg/kg of FIP technical grade by oral gavage, daily for 45 days. Brain stem and diencephalon were processed to examine oxidative stress-induced macromolecular alteration (MDA, PCC and DNA fragmentation). Also, the histopathological assessment and immunoreactivity for caspase-3 (active form), iNOS and GFAP were performed on the thalamus, hypothalamus and medulla oblongata. Our results revealed that FIP significantly raised MDA, PCC and DNA fragmentation (p ≤ 0.05). In addition, significantly increased immunoreactivity to GFAP, iNOS and caspase-3 (active form) in the FIP-treated group was noticed (p ≤ 0.05). Moreover, alterations in the histoarchitecture of the neural tissue of these regions were observed. We conclude that FIP can induce oxidative stress, leading to apoptosis and tissue reaction in brain stem and diencephalon.
Assuntos
Apoptose , Tronco Encefálico/patologia , Diencéfalo/patologia , Estresse Oxidativo , Pirazóis/toxicidade , Animais , Apoptose/efeitos dos fármacos , Tronco Encefálico/efeitos dos fármacos , Diencéfalo/efeitos dos fármacos , Inseticidas/toxicidade , Masculino , Estresse Oxidativo/efeitos dos fármacos , RatosRESUMO
Mutations in the human PTEN-induced kinase 1 (PINK1) gene are linked to recessive familial Parkinson's disease. Animal models of altered PINK1 function vary greatly in their phenotypic characteristics. Drosophila pink1 mutants exhibit mild dopaminergic neuron degeneration and locomotion defects. Such defects are not observed in mice with targeted null mutations in pink1, although these mice exhibit impaired dopamine release and synaptic plasticity. Here, we report that in zebrafish, morpholino-mediated knockdown of pink1 function did not cause large alterations in the number of dopaminergic neurons in the ventral diencephalon. However, the patterning of these neurons and their projections are perturbed. This is accompanied by locomotor dysfunction, notably impaired response to tactile stimuli and reduced swimming behaviour. All these defects can be rescued by expression of an exogenous pink1 that is not a target of the morpholinos used. These results indicate that normal PINK1 function during development is necessary for the proper positioning of populations of dopaminergic neurons and for the establishment of neuronal circuits in which they are implicated.
Assuntos
Diencéfalo/crescimento & desenvolvimento , Proteínas Quinases/genética , Natação/fisiologia , Percepção do Tato/fisiologia , Peixe-Zebra , Sequência de Aminoácidos , Animais , Diencéfalo/anatomia & histologia , Diencéfalo/efeitos dos fármacos , Diencéfalo/metabolismo , Dopamina/metabolismo , Larva/efeitos dos fármacos , Larva/fisiologia , Dados de Sequência Molecular , Neurônios/metabolismo , Neurônios/fisiologia , Oligonucleotídeos Antissenso/farmacologia , Proteínas Quinases/metabolismoRESUMO
Goldfish (Carassius auratus) use reproductive hormones as endocrine signals to synchronize sexual behavior with gamete maturation and as exogenous signals (pheromones) to mediate spawning interactions between conspecifics. We examined the differential effects of two hormonal pheromones, prostaglandin F(2alpha) (PGF(2alpha)) and 17alpha,20beta-dihydroxy-4-pregnen-3-one (17,20beta-P) on neurogenesis, neurotransmission, and neuronal activities, and on plasma androstenedione (AD) levels. Exposure to waterborne PGF(2alpha) induced a multitude of changes in male goldfish brain. Histological examination indicated an increase in the number of dividing cells in male diencephalon (p < 0.05, Kruskal-Wallis test). Real-time quantitative PCR tests showed elevated levels of transcripts for the salmon gonadotropin-releasing hormone (GnRH) in the male telencephalon and cerebellum (p < 0.005, one-way ANOVA) and for ChAT (choline acetyltransferase) in the male vagal lobe and the brainstem underneath the vagal lobe (p < 0.05, one-way ANOVA). Therefore, PGF(2alpha) seemed to modulate male brain plasticity that coincided with behavioral changes during spawning season. Exposure to waterborne 17,20beta-P, however, increased circulatory levels of immunoreactive AD in males and the transcripts of androgen receptor and cGnRH-II (chicken-II GnRH) in the female cerebellum (p < 0.05, one-way ANOVA). PGF(2alpha) and 17,20beta-P thereby seemed to act through distinct pathways to elicit different responses in the neuroendocrine system. This is the first finding that links a specific pheromone molecule (PGF(2alpha)) to neurogenesis in a vertebrate animal.
Assuntos
Dinoprosta/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/metabolismo , Hidroxiprogesteronas/farmacologia , Neurogênese/efeitos dos fármacos , Análise de Variância , Androstenodiona/sangue , Animais , Química Encefálica/efeitos dos fármacos , Colina O-Acetiltransferase/genética , Colina O-Acetiltransferase/metabolismo , Diencéfalo/citologia , Diencéfalo/efeitos dos fármacos , Glutamato Descarboxilase/genética , Glutamato Descarboxilase/metabolismo , Carpa Dourada/fisiologia , Hormônio Liberador de Gonadotropina/genética , Masculino , Neurotransmissores/genética , Neurotransmissores/metabolismo , RNA Mensageiro/metabolismo , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismoRESUMO
Injection of 6 micrograms of aqueous norepinephrine elicits eating only when it takes place at sites within a limited region of the rat brain. The distribution of effective sites coincides with that of systems connected to an extrahypothalamic pathway between the limbic forebrain and tegmental motor systems. It does not correspond to those parts of the lateral hypothalamus thought to control normal feeding.
Assuntos
Diencéfalo/fisiologia , Fome , Norepinefrina/farmacologia , Sistema Nervoso Simpático/fisiologia , Animais , Comportamento Animal , Diencéfalo/efeitos dos fármacos , Ingestão de Alimentos , Estimulação Elétrica , RatosRESUMO
Adrenergic and cholinergic stimulation of several interrelated limbic and diencephalic areas causes the animal to eat and drink, respectively. The brain areas involved may be organized in terms of "Papez circuit" and, more generally, " Nauta circuit" neuroanatomy. However, it is proposed that separate synaptic nets, one for the control of hunger and one for the control of thirst, are deployed throughout the brain at all levels, including neocortical.
Assuntos
Carbacol/farmacologia , Diencéfalo/fisiologia , Hipocampo/fisiologia , Hipotálamo/fisiologia , Sistema Límbico/fisiologia , Norepinefrina/farmacologia , Tálamo/fisiologia , Animais , Diencéfalo/efeitos dos fármacos , Ingestão de Líquidos , Ingestão de Alimentos , Sistema Límbico/efeitos dos fármacos , Masculino , Ratos , Técnicas EstereotáxicasRESUMO
Naloxone hydrochloride, an opioid antagonist, was applied to several discrete brain regions of morphine-dependent rats to precipitate abstinence. Severe withdrawal signs were elicited after administration in the thalamus but not in neocortical, hippocampal, hypothalamic, or tegmental areas of the brain.
Assuntos
Encéfalo/efeitos dos fármacos , Morfinanos/farmacologia , Dependência de Morfina , Antagonistas de Entorpecentes/farmacologia , Animais , Córtex Cerebral/efeitos dos fármacos , Diencéfalo/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Humanos , Hipotálamo/efeitos dos fármacos , Masculino , Mesencéfalo/efeitos dos fármacos , Morfina/farmacologia , Naloxona/administração & dosagem , Naloxona/farmacologia , Ratos , Técnicas Estereotáxicas , Síndrome de Abstinência a Substâncias/induzido quimicamente , Tálamo/efeitos dos fármacosRESUMO
The discovery of two novel avian neurosteroids in the quail brain, 7alpha- and 7beta-hydroxypregnenolone is described. Intracerebroventricular administration of 7alpha-hydroxypregnenolone, but not 7beta-hydroxypregnenolone was found to stimulate locomotor activity of male quail when spontaneous nocturnal activity is low. Diurnal changes in locomotor activity in male quail were found to be correlated with a diurnal change in the concentration of diencephalic 7alpha-hydroxypregnenolone. This correlation was a not seen in female quail which have a lower amplitude diurnal rhythm of locomotor activity and lower daytime concentrations of diencephalic 7alpha-hydroxypregnenolone. Treatment of male quail with melatonin was found to depress the synthesis of 7alpha-hydroxypregnenolone in the diencephalon. This is a previously undescribed role for melatonin in the regulation of neurosteroid synthesis in the brain of any vertebrate. We therefore deduced in male quail, that the nocturnal depression in locomotory activity is a consequence of a depression in diencephalic 7alpha-hydroxypregnenolone resulting from the inhibitory action of the nocturnal increase in melatonin. This observation may be of widespread significance for the molecular control of rhythmic locomotor activity in all vertebrates.
Assuntos
17-alfa-Hidroxipregnenolona/análogos & derivados , Ritmo Circadiano/fisiologia , Coturnix/fisiologia , Atividade Motora/fisiologia , 17-alfa-Hidroxipregnenolona/metabolismo , Animais , Coturnix/metabolismo , Diencéfalo/efeitos dos fármacos , Diencéfalo/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Melatonina/metabolismo , Melatonina/farmacologiaRESUMO
BACKGROUND: Recent data have demonstrated that treatment with sodium benzoate (SB) leads to significant developmental defects in motor neuron axons and neuromuscular junctions in zebrafish larvae, thereby implying that SB can be neurotoxic. This study examined whether SB affects the development of dopaminergic neurons in the zebrafish brain. METHODS: Zebrafish embryos were exposed to different concentrations of SB for various durations, during which the survival rates were recorded, the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) in the neurons in the ventral diencephalon were detected by in situ hybridization and immunofluorescence, and the locomotor activity of larval zebrafish was measured. RESULTS: The survival rates were significantly decreased with the increase of duration and dose of SB-treatment. Compared to untreated clutch mates (untreated controls), treatment with SB significantly downregulated expression of TH and DAT in neurons in the ventral diencephalon of 3-day post-fertilization (dpf) zebrafish embryos in a dose-dependent manner. Furthermore, there was a marked decrease in locomotor activity in zebrafish larvae at 6dpf in response to SB treatment. CONCLUSIONS: The results suggest that SB exposure can cause significantly decreased survival rates of zebrafish embryos in a time- and dose-dependent manner and downregulated expression of TH and DAT in dopaminergic neurons in the zebrafish ventral diencephalon, which results in decreased locomotor activity of zebrafish larvae. This study may provide some important information for further elucidating the mechanism underlying SB-induced developmental neurotoxicity.
Assuntos
Diencéfalo/efeitos dos fármacos , Proteínas da Membrana Plasmática de Transporte de Dopamina/biossíntese , Conservantes de Alimentos/toxicidade , Neurônios/efeitos dos fármacos , Benzoato de Sódio/toxicidade , Tirosina 3-Mono-Oxigenase/biossíntese , Proteínas de Peixe-Zebra/biossíntese , Peixe-Zebra/embriologia , Animais , Sequência de Bases , DNA Complementar/genética , Diencéfalo/embriologia , Diencéfalo/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Indução Enzimática/efeitos dos fármacos , Hibridização In Situ , Larva/efeitos dos fármacos , Microscopia de Fluorescência , Dados de Sequência Molecular , Neurônios/metabolismo , Distribuição Aleatória , Natação , Tirosina 3-Mono-Oxigenase/genética , Proteínas de Peixe-Zebra/genéticaRESUMO
In mammals, anorexia accompanying infection is thought to be mediated via cytokines including interleukins, interferons (IFNs), and tumor necrosis factor (TNF). However, there is a lack of related knowledge on birds. Therefore, the purpose of the present study was to determine if cytokines are associated with reduced food intake in chicks (Gallus gallus). Specifically, we evaluated the effects of TNF-like cytokine 1A (TL1A), a member of the TNF family, interferon-α (IFN-α), and interferon-γ (IFN-γ) on food intake. Additionally, the effect of lipopolysaccharide (LPS) and polyinosinic:polycytidylic acid (poly I:C) on cytokine mRNA expression in the diencephalon and spleen was also measured. Intracerebroventricular (ICV) injection of 0.05 or 0.5⯵g TL1A, IFN-α, and IFN-γ had no effect on food intake. However, when 1.0⯵g each of these factors was evaluated, TL1A significantly decreased food intake at 180 and 240â¯min after the injection, but IFN-α and IFN-γ had no effect. When chicks received intraperitoneal (IP) injections of 100⯵g LPS or 400⯵g poly I:C, their food intake was reduced. Diencephalic mRNA expression of TL1A was significantly decreased following IP injection of LPS or poly I:C. Additionally, diencephalic mRNA expression of IFN-γ mRNA was significantly increased by IP injection of LPS but decreased by IP injection of poly I:C. For the spleen, IP injection of LPS and poly I:C both significantly increased TL1A and IFN-γ mRNA expression. In sum, we have provided evidence that central TL1A but not IFN-α or IFN-γ are related to reduction of food intake in chicks, but the role of these cytokines for mediating anorexia associated with infections may differ from mammals.
Assuntos
Anorexia/imunologia , Ingestão de Alimentos/imunologia , Interferon-alfa/metabolismo , Interferon gama/metabolismo , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo , Animais , Anorexia/etiologia , Galinhas , Diencéfalo/efeitos dos fármacos , Diencéfalo/imunologia , Ingestão de Alimentos/efeitos dos fármacos , Comportamento de Doença/fisiologia , Interferon-alfa/administração & dosagem , Interferon gama/administração & dosagem , Lipopolissacarídeos , Masculino , Poli I-C , RNA Mensageiro/metabolismo , Baço/efeitos dos fármacos , Baço/imunologia , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/administração & dosagemRESUMO
Restless legs syndrome (RLS) is a common neurologic condition involving iron and dopamine systems. We sought to create an animal model consistent with RLS based on current understanding of human pathology. We performed bilateral 6-hydroxydopamine (6-OHDA) lesioning in the A11 nucleus of C57BL/6 mice and deprived a subset of mice from dietary iron to observe whether these manipulations can increase motor activity. Iron levels in serum, brain, and especially spinal cord were significantly decreased after iron deprivation. Interestingly, 6-OHDA lesioning appeared to further reduce CNS iron stores. Pathologic examination demonstrated a 94% reduction in A11 tyrosine hydroxylase staining cells in mice injected with 6-OHDA but minimal effects on other areas. Locomotor activities were significantly increased in both the mice that were iron deprived and the A11-lesioned mice compared with controls. The combination of iron deprivation and A11 lesions further significantly augmented activity. Additionally, the mice in the combined iron-deprived and lesioned group were more aggressive. The increased activity in A11-lesioned mice with or without iron deprivation was normalized after treatment with the D2/D3 agonist ropinirole, as is seen in human RLS but was worsened by the D1 agonist SKF38393. This model could be consistent with human RLS, attention deficit hyperactivity disorder, or akathisia.
Assuntos
Lesões Encefálicas/patologia , Lesões Encefálicas/fisiopatologia , Diencéfalo/patologia , Deficiências de Ferro , Locomoção/fisiologia , Animais , Lesões Encefálicas/induzido quimicamente , Lesões Encefálicas/metabolismo , Diencéfalo/efeitos dos fármacos , Diencéfalo/metabolismo , Modelos Animais de Doenças , Agonistas de Dopamina/farmacologia , Indóis/farmacologia , Ferro/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oxidopamina , Síndrome das Pernas Inquietas , Medula Espinal/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Leptin administration inhibits diencephalic nitric oxide synthase (NOS) activity and increases brain serotonin (5-HT) metabolism in mice. We evaluated food intake, body-weight gain, diencephalic NOS activity, and diencephalic content of tryptophan (TRP), 5-HT, hydroxyindoleacetic acid (5-HIAA), and 5-HIAA/5-HT ratio after intracerebroventricular (ICV) or intraperitoneal (IP) leptin injection in mice. Five consecutive days of ICV or IP leptin injections induced a significant reduction in neuronal NOS (nNOS) activity, and caused a dose-dependent increase of 5-HT, 5-HIAA, and the 5-HIAA/5-HT ratio. Diencephalic 5-HT metabolism showed a significant increase in 5-HT, 5-HIAA, and the 5-HIAA/5-HT ratio 3 hours after a single leptin injection. This effect was maintained for 3 hours and had disappeared by 12 hours after injection. After a single IP leptin injection, the peak for 5-HT, 5-HIAA, and the 5-HIAA/5-HT ratio was achieved at 6 hours. Single injections of ICV or IP leptin significantly increased diencephalic 5-HT content. Leptin-induced 5-HT increase was antagonized by the coadministration of L-arginine only when the latter was ICV injected, whereas D-arginine did not influence leptin effects on brain 5-HT content. Finally, in nNOS-knockout mice, the appetite-suppressant activity of leptin was strongly reduced, and the leptin-induced increase in brain 5-HT metabolism was completely abolished. Our results indicate that the L-arginine/NO pathway is involved in mediating leptin effects on feeding behavior, and demonstrate that nNOS activity is required for the effects of leptin on brain 5-HT turnover.