RESUMO
Detecting neurodevelopµental disorders of cognition at the earliest possible stages could assist in understanding them mechanistically and ultimately in treating them. Finding early physiological predictors that could be visualized with functional neuroimaging would represent an important advance in this regard. We hypothesized that one potential source of physiological predictors is the spontaneous local network activity prominent during specific periods in development. To test this we used calcium imaging in brain slices and analyzed variations in the frequency and intensity of this early activity in one area, the entorhinal cortex (EC), in order to correlate early activity with level of cognitive function later in life. We focused on EC because of its known role in different types of cognitive processes and because it is an area where spontaneous activity is prominent during early postnatal development in rodent models of cortical development. Using rat strains (Long-Evans, Wistar, Sprague-Dawley and Brattleboro) known to differ in cognitive performance in adulthood we asked whether neonatal animals exhibit corresponding strain-related differences in EC spontaneous activity. Our results show significant differences in this activity between strains: compared to a high cognitive-performing strain, we consistently found an increase in frequency and decrease in intensity in neonates from three lower performing strains. Activity was most different in one strain considered a model of schizophrenia-like psychopathology. While we cannot necessarily infer a causal relationship between early activity and adult cognition our findings suggest that the pattern of spontaneous activity in development could be an early predictor of a developmental trajectory advancing toward sub-optimal cognitive performance in adulthood. Our results further suggest that the strength of dopaminergic signaling, by setting the balance between excitation and inhibition, is a potential underlying mechanism that could explain the observed differences in early spontaneous activity patterns.
Assuntos
Córtex Cerebral/crescimento & desenvolvimento , Cognição/fisiologia , Rede Nervosa/crescimento & desenvolvimento , Fatores Etários , Animais , Animais Recém-Nascidos/anatomia & histologia , Animais Recém-Nascidos/crescimento & desenvolvimento , Córtex Entorrinal/anatomia & histologia , Córtex Entorrinal/crescimento & desenvolvimento , Rede Nervosa/anatomia & histologia , Rede Nervosa/fisiologia , Ratos , Ratos Brattleboro/crescimento & desenvolvimento , Ratos Brattleboro/fisiologia , Ratos Long-Evans/crescimento & desenvolvimento , Ratos Long-Evans/fisiologia , Ratos Sprague-Dawley/crescimento & desenvolvimento , Ratos Sprague-Dawley/fisiologia , Ratos Wistar/crescimento & desenvolvimento , Ratos Wistar/fisiologia , Receptores de Dopamina D1/fisiologia , Receptores de Dopamina D5/fisiologia , Receptores de GABA-A/fisiologia , Especificidade da EspécieRESUMO
Early mother-infant relationships exert important long-term effects in offspring and are disturbed by factors such as postpartum depression. We aimed to clarify if lack of vasopressin influences maternal behavior paralleled by the development of a depressive-like phenotype. We compared vasopressin-deficient Brattleboro mothers with heterozygous and homozygous normal ones. The following parameters were measured: maternal behavior (undisturbed and separation-induced); anxiety by the elevated plus maze; sucrose and saccharin preference and forced swim behavior. Underlying brain areas were examined by c-fos immunocytochemistry among rest and after swim-stress. In another group of rats, vasopressin 2 receptor agonist was used peripherally to exclude secondary changes due to diabetes insipidus. Results showed that vasopressin-deficient rats spend less time licking-grooming their pups through a centrally driven mechanism. There was no difference between genotypes during the pup retrieval test. Vasopressin-deficient mothers tended to explore more the open arms of the plus maze, showed more preference for sucrose and saccharin and struggled more in the forced swim test, suggesting that they act as less depressive. Under basal conditions, vasopressin-deficient mothers had more c-fos expression in the medial preoptic area, shell of nucleus accumbens, paraventricular nucleus of the hypothalamus and amygdala, but not in other structures. In these areas the swim-stress-induced activation was smaller. In conclusion, vasopressin-deficiency resulted in maternal neglect due to a central effect and was protective against depressive-like behavior probably as a consequence of reduced activation of some stress-related brain structures. The conflicting behavioral data underscores the need for more sex specific studies.
Assuntos
Comportamento Animal/fisiologia , Comportamento Materno/fisiologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos Brattleboro , Vasopressinas/fisiologia , Animais , Mapeamento Encefálico , Sistema Nervoso Central/metabolismo , Depressão/metabolismo , Depressão/fisiopatologia , Depressão/psicologia , Feminino , Comportamento Materno/psicologia , Aprendizagem em Labirinto , Modelos Biológicos , Mães/psicologia , Ratos , Ratos Brattleboro/metabolismo , Ratos Brattleboro/fisiologia , Ratos Transgênicos , Natação/fisiologia , Vasopressinas/genética , Vasopressinas/metabolismoRESUMO
BACKGROUND: Brattleboro rats (BRATs) have natural deficits in prepulse inhibition (PPI) of the startle response similar to those exhibited by schizophrenia patients, which are reversed by antipsychotics. We sought to determine whether they also have increases in striatal dopamine-2 (D2) receptors found in some studies examining the brains of schizophrenia patients. METHODS: Several days after startle testing, the brains of BRAT and Long Evans (LE) rats were removed, and D1 and D2 receptor levels were measured by autoradiography. RESULTS: PPI was lower in BRATs consistent with previous reports. D2, but not D1, receptor binding was significantly higher in the nucleus accumbens shell and the dorsomedial caudate of BRAT compared with LE rats, consistent with some findings in schizophrenia patients. Furthermore, individual rat PPI was inversely correlated with D2 binding density. CONCLUSIONS: These findings suggest that the dopamine system in BRATs is dysregulated and these abnormalities may contribute to the PPI deficits observed in these rats.
Assuntos
Corpo Estriado/metabolismo , Inibição Neural/fisiologia , Ratos Brattleboro/fisiologia , Receptores de Dopamina D2/metabolismo , Reflexo de Sobressalto/fisiologia , Regulação para Cima/fisiologia , Estimulação Acústica/métodos , Análise de Variância , Animais , Comportamento Animal , Relação Dose-Resposta à Radiação , Inibição Neural/efeitos da radiação , Ratos , Ratos Long-Evans , Receptores de Dopamina D1/metabolismoRESUMO
In puromycin aminonucleoside (PAN)-treated nephrotic rats, sodium retention is associated with increased (Na+/K+)-ATPase activity in the cortical collecting ducts (CCD). This study was undertaken to determine whether stimulation of (Na+/K+)-ATPase in the CCD is a feature of other experimental nephrotic syndromes, whether it might be responsible for renal sodium retention, and whether it is mediated by increased plasma vasopressin levels or activation of calcineurin. For this purpose, the time courses of urinary excretion of sodium and protein, sodium balance, ascites, and (Na+/K+)-ATPase activities in microdissected CCD were studied in rats with PAN or adriamycin nephrosis or HgCl2 nephropathy. The roles of vasopressin and calcineurin in PAN nephrosis were evaluated by measuring these parameters in Brattleboro rats and in rats treated with cyclosporin or tacrolimus. Despite different patterns of changes in urinary sodium and protein excretion in the three nephrotic syndrome models, there was a linear relationship between CCD (Na+/K+)-ATPase activities and sodium excretion in all three cases. The results also indicated that there was no correlation between proteinuria and sodium retention, but ascites was present only when proteinuria was associated with marked reduction of sodium excretion. Finally, the lack of vasopressin in Brattleboro rats or the inhibition of calcineurin by administration of either cyclosporin or tacrolimus did not prevent development of the nephrotic syndrome in PAN-treated rats or stimulation of CCD (Na+/K+)-ATPase. It is concluded that stimulation of Na(+/K+)-ATPase in the CCD of nephrotic rats might be responsible for sodium retention and that this phenomenon is independent of proteinuria and vasopressin and calcineurin activities.
Assuntos
Túbulos Renais Coletores/enzimologia , Natriurese , Síndrome Nefrótica/fisiopatologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Animais , Calcineurina/fisiologia , Doxorrubicina , Glomerulonefrite Membranosa/induzido quimicamente , Glomerulonefrite Membranosa/enzimologia , Glomerulonefrite Membranosa/fisiopatologia , Masculino , Cloreto de Mercúrio , Nefrose/induzido quimicamente , Nefrose/enzimologia , Nefrose/fisiopatologia , Síndrome Nefrótica/induzido quimicamente , Síndrome Nefrótica/enzimologia , Puromicina Aminonucleosídeo , Ratos , Ratos Brattleboro/fisiologia , Ratos Endogâmicos BN , Ratos Long-Evans/fisiologia , Ratos Sprague-Dawley/fisiologia , Fatores de TempoRESUMO
Arginine vasopressin (AVP) plays an important role in the expression of aquaporin (AQP-2) in the collecting duct. The present study was undertaken to determine whether there is an AVP-independent regulation of AQP-2 gene expression in homozygous Brattleboro rats in which endogenous AVP is absent. Exogenous administration of 1-deamino-8-D-AVP produced an antidiuresis and expressed AQP-2 mRNA and AQP-2 protein in the renal medulla of the homozygous Brattleboro rats. Twelve hours of water deprivation produced severe dehydration in the homozygous Brattleboro rats, such that urinary osmolality increased from 200 to 649 mosmol/kgH(2)O. However, no increase in AQP-2 mRNA expression was observed after this dehydration, and the medullary tissue content and urinary excretion of AQP-2 also remained unchanged. Increases in AQP-2 mRNA expression and AQP-2 protein were evident in Long-Evans rats after 64 h of water deprivation, with a severity of dehydration almost equal to the 12-h dehydrated, homozygous Brattleboro rats. These results indicate the lack of an AVP-independent mechanism for upregulating AQP-2 mRNA expression in renal collecting duct cells.
Assuntos
Aquaporinas/genética , Arginina Vasopressina/fisiologia , Regulação da Expressão Gênica , Homozigoto , Ratos Brattleboro/genética , Animais , Aquaporina 2 , Aquaporina 6 , Aquaporinas/metabolismo , Desamino Arginina Vasopressina/farmacologia , Desidratação/urina , Diurese/efeitos dos fármacos , Medula Renal/metabolismo , Masculino , Concentração Osmolar , RNA Mensageiro/metabolismo , Ratos , Ratos Brattleboro/fisiologia , Ratos Long-Evans , Fármacos Renais/farmacologia , Privação de Água/fisiologiaRESUMO
Behavioral neuroscience is using more and more gene knockout techniques to produce animals with a specific deletion. These studies have their precedent in nature. A mutation may result in a limited genetic defect, as seen in the vasopressin (VP) deficiency in the Brattleboro rat. The mutation is in a single pair of autosomal loci, and the sequences of VP gene from wild-type and homozygous Brattleboro rats are identical except for a single nucleotide deletion in the second exon. The deletion results in the synthesis of an altered VP precursor that is unable to enter the secretory pathway. The genetic disturbance results in a central diabetes insipidus comparable to that found in humans. Starting with our work during the early 1970s we found that the genetic defect in the availability of VP causes deficits in central nervous system (CNS) functions. Behavioral processes from cognition to drug tolerance appeared to be disturbed by the absence of VP, but not all behaviors are affected. The specificity of the absence of VP in causing behavioral deficits is shown in many cases. However, certain deficits are due to genetic factors other than the deletion of the VP gene. The picture is further complicated by differences in testing conditions, the absence of proper controls, i.e. heterozygous and wild-type Brattleboro rats, sex, compensation phenomena, and the absence of neuropeptides co-localized with VP. Interestingly, an age dependent spontaneous shunt to a heterozygous phenotype in vasopressinergic neurons might also compensate for the disturbance. Accordingly, findings in knockout animals should be interpreted with caution. One should realize that brain functions are modulated by multiple neuropeptides and that neuropeptides possess multiple CNS effects.
Assuntos
Química Encefálica/genética , Deleção de Genes , Sistemas Neurossecretores/fisiopatologia , Ratos Brattleboro/fisiologia , Vasopressinas/genética , Animais , RatosRESUMO
Regulation of the number of pituitary vasopressin (VP) receptors plays an important role in controlling pituitary responsiveness during alterations of the hypothalamic pituitary adrenal axis. The mechanisms regulating these VP receptors were studied by analysis of the effects of adrenalectomy and glucocorticoid administration on V1b receptor (V1b-R) messenger RNA (mRNA) by Northern blot and by in situ hybridization in the rat. Adrenalectomy transiently decreased V1b-R mRNA levels by 18 h (77% and 62% for the 3.7-kb and 3.2-kb bands in the Northern blots, and 50% by in situ hybridization), returning to basal levels after 6 days. The decrease in V1b-R mRNA after 18 h adrenalectomy was fully prevented by dexamethasone (100 microg s.c.) but not by elimination of hypothalamic CRH and VP by paraventricular nucleus lesions or median eminence deafferentation. In sham-operated rats, dexamethasone increased receptor mRNA by 50% after 6 days. In contrast to Sprague-Dawley rats, in Brattleboro rats (di/di), which lack hypothalamic VP, adrenalectomy caused a sustained decrease in V1b-R mRNA levels (<50% of controls by 6 days). The data show that pituitary V1b-R mRNA is positively regulated by glucocorticoids and that the recovery of V1b-R mRNA levels after prolonged adrenalectomy is probably mediated by VP. In addition, the data suggest that the down-regulation of VP binding after long-term adrenalectomy is due to posttranscriptional events rather than to changes in V1b-R mRNA.
Assuntos
Adrenalectomia , Glucocorticoides/farmacologia , Hipófise/metabolismo , RNA Mensageiro/fisiologia , Receptores de Vasopressinas/genética , Vias Aferentes/fisiologia , Animais , Denervação , Diabetes Mellitus/genética , Diabetes Mellitus/fisiopatologia , Masculino , Núcleo Hipotalâmico Paraventricular/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Brattleboro/genética , Ratos Brattleboro/fisiologia , Ratos Sprague-DawleyRESUMO
Defects in peptide processing are associated with several disorders, including central diabetes insipidus (CDI). In the Brattleboro (BB) rat with CDI, the mRNA and protein of arginine vasopressin (AVP) are present in the hypothalamus, but no circulating AVP is detectable, thus suggesting a processing defect. The present study examined AVP secretion in cultured COS cells transfected with various constructs from wild-type and mutated Brattleboro AVP gene precursors. The precursor contains three exons encoding for vasopressin (VP), neurophysin (NP), and glycopeptide (GP). The Brattleboro rat has a deletion of a single base, guanine (G), in the NP coding region that leads to a frameshift, resulting in the loss of normal stop codon. The wild-type pcVP (22.0 +/- 5.2 pg/10[-2] U beta-galactosidase [beta-gal]), but not the mutated BB AVP gene pcBB (1.2 +/- 0.4 pg/10[-2] U beta-gal), was associated with AVP secretion from the COS cells as measured by RIA. The wild-type AVP gene without the GP coding region was associated with AVP release greater (47.4 +/- 13.5 pg/10[-2] U beta-gal, n = 5, P < 0.05, versus pcVP) than the pcVP with intact VP, NP, and GP coding regions. However, the wild-type AVP gene with VP coding region alone was not processed and secreted. Normalizing the pcBB total length with the insertion of a stop codon at the site of the normal stop codon was not associated with AVP secretion (3.0 +/- 1.4 pg/10[-2] U beta-gal). However, insertion of a stop codon so that the pcBB length equaled the length of VP and NP coding regions of the wild type was associated with AVP secretion (13.5 +/- 4.0 pg/10[-2] U beta-gal). When a stop codon was inserted into the wild-type NP coding region at the same site as the G deletion in the pcBB, the AVP secretion was significantly lower (15.1 +/- 5.0 pg/10[-2] U beta-gal) than pcVP with VP + NP but no GP coding regions (47.4 +/- 13.5 pg/10[-2] U beta-gal, n = 5, P < 0.05). In summary, (1) both VP and intact NP, but not GP, coding regions are necessary for AVP processing and secretion; (2) decreasing the length of the NP coding region diminishes but does not abolish AVP processing and secretion; and (3) shortening of the pcBB length with a stop codon at a site comparable to wild-type VP + NP allows AVP secretion, albeit less than with wild-type gene precursor. Thus, the CDI in BB rats is caused by the G deletion in NP coding region. This defect leads to abnormalities that contribute to the abnormal AVP processing. Specifically, the frameshift and absence of a stop codon cause a mutated extended C terminus, which, along with the mutated NP, contribute to the abnormal steps of AVP processing, transport, and secretion in the BB rat. These defects no doubt impair the folding and configuration necessary for normal processing of the AVP gene precursor.
Assuntos
Arginina Vasopressina/genética , Diabetes Insípido/genética , Precursores de Proteínas/metabolismo , Processamento de Proteína Pós-Traducional , Ratos Brattleboro/fisiologia , Animais , Arginina Vasopressina/química , Arginina Vasopressina/deficiência , Arginina Vasopressina/metabolismo , Células COS/metabolismo , Códon/genética , DNA Complementar/genética , Mutação da Fase de Leitura , Conformação Proteica , RNA Mensageiro/genética , Ratos , Ratos Brattleboro/genética , Proteínas Recombinantes de Fusão/metabolismo , Taxa Secretória , Regiões Terminadoras Genéticas , TransfecçãoRESUMO
Brain natriuretic peptide (BNP) messenger RNA was measured with a semiquantitative method from heart auricles and ventricles of vasopressin-deficient Brattleboro rats (DI) and from desmopressin treated Brattleboro rats (DI + DDAVP). Desmopressin had been injected peripherally and Long-Evans rats (LE) served as controls. The 3-day substitution treatment had shifted the fluid balance of DI almost to that of LE. In the present study, the amount of BNP mRNA, normalized to the glyceraldehyde-3-phosphate dehydrogenase mRNA content, was constant in all three groups in the right auricle. No changes were when the right auricular and left auricular mRNA levels were compared within each group. In the left auricle, desmopressin treatment increased significantly (P < 0.05) the amount of BNP mRNA compared with that of LE rats (from 1.09 +/- 0.21, n = 7 to 1.72 +/- 0.17, n = 8, arbitrary units). In all groups, the left ventricle had significantly (P < 0.05) higher mRNA content than the right ventricle (LE: 2.24 +/- 0.23 vs. 0.67 +/- 0.13, n = 6; DI: 2.30 +/- 0.60 vs. 0.33 +/- 0.05, n = 8; DI + DDAVP: 2.36 +/- 0.29 vs. 0.37 +/- 0.07, n = 10). In the right ventricle, both DI and DI + DDAVP rats had significantly (P < 0.05) lower mRNA content than LE rats (0.33 +/- 0.5 vs. 0.67 +/- 0.13 and 0.37 +/- 0.07 vs. 0.67 +/- 0.13, respectively). To conclude, these findings suggest that brain natriuretic peptide gene expression dissociates from, or rapidly adapts to, the chronic effects of peripheral desmopressin treatment which have shifted the fluid balance to almost normal in Brattleboro rats. The left ventricular pressure appears to regulate the brain natriuretic peptide gene expression.
Assuntos
Miocárdio/química , Proteínas do Tecido Nervoso/genética , Ratos Brattleboro/fisiologia , Vasopressinas/genética , Animais , Desamino Arginina Vasopressina/farmacologia , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/fisiologia , Immunoblotting , Masculino , Miocárdio/metabolismo , Peptídeo Natriurético Encefálico , RNA Mensageiro/análise , Ratos , Fármacos Renais/farmacologia , Vasopressinas/deficiência , Equilíbrio Hidroeletrolítico/fisiologiaRESUMO
There is increasing evidence that ovarian steroids inhibit vascular responsiveness to the neurohypophysial hormone vasopressin. The present study examined the recovery of the arterial blood pressure following a single (2 ml/100 g body weight) haemorrhage in ovariectomized (OVX) Brattleboro rats with hereditary hypothalamic diabetes insipidus (BDI) and rats of the parent Long Evans (LE) strain. Some groups of OVX rats received subcutaneous implants of either 17 beta-oestradiol (E2) or progesterone 7 days prior to haemorrhage. The arterial blood pressure recovery immediately following haemorrhage was significantly impaired in both groups of steroid-treated OVX LE rats compared with the OVX controls (both comparisons P < 0.05). The impairment in blood pressure recovery seen in the steroid-replaced OVX LE rats was similar to that seen in pro-oestrous rats (when ovarian steroid levels are raised) compared with male rats of this strain (P < 0.05). In contrast, ovariectomy with or without steroid replacement in BDI rats had no further effect on the already attenuated recovery of arterial blood pressure after haemorrhage in this strain. Heart rate responses to haemorrhage also showed strain differences, which were dependent on steroid treatment. Pro-oestrous female LE rats showed a small decrease in heart rate after haemorrhage, followed by a recovery process, and this initial bradycardia was markedly enhanced in the OVX steroid-treated animals. In contrast, untreated OVX LE rats showed an initial and sustained increase in heart rate which was significantly higher than in the steroid-treated OVX animals (P < 0.05). All BDI rats, irrespective of treatment, consistently showed an increased heart rate after haemorrhage. In conclusion, ovarian steroid replacement in OVX LE, but not vasopressin-deficient BDI, rats was associated with an attenuated pressor recovery after haemorrhage. This provides further evidence for the existence of an important inhibitory interaction between ovarian steroids and vasopressin. The initial decrease in heart rate observed in pro-oestrous and steroid-treated OVX LE rats after haemorrhage also appears to be related to an ovarian steroid-vasopressin interaction.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Diabetes Insípido/fisiopatologia , Estradiol/farmacologia , Hemorragia/fisiopatologia , Ovariectomia , Progesterona/farmacologia , Ratos Brattleboro/fisiologia , Animais , Feminino , Frequência Cardíaca , Masculino , Ratos , Ratos Endogâmicos , Ratos Mutantes , Vasopressinas/deficiênciaRESUMO
A sexual dimorphism in the pressor responsiveness to the neurohypophysial hormone vasopressin may be associated with a peripheral interaction between ovarian steroids and the neurohypophysial hormone. Indeed, the ovarian steroids may inhibit the vasopressin-dependent component of the pressor response to haemorrhage. The present study examined the recovery of the arterial blood pressure following it single large (2% v/w) haemorrhage in anaesthetized male Long Evans (LE) rats and females of the same strain during either pro-oestrous or di-oestrous phases of the reproductive cycle. In addition the same recovery process was examined in Brattleboro rats with diabetes insipidus (BDI) lacking circulating vasopressin. All BDI rats had an impaired blood pressure recovery following haemorrhage compared with male rats of the parent LE strain, and this was irrespective of sex or stage of the oestrous cycle. While the blood pressure recovery was more impaired in both groups of BDI female rats than in the males of the same strain during the first 20 min after haemorrhage (both comparisons p < 0.001; ANOVA), there was no difference between the recoveries of the female rats in pro-oestrus or di-oestrus. In contrast a significantly impaired blood pressure recovery was observed in female LE rats at pro-oestrus, when circulating ovarian steroid concentrations are raised, compared with male (p < 0.001: ANOVA) and di-oestrous (p < 0.02: ANOVA) rats of the same strain. Heart rate responses to haemorrhage showed strain differences, with LE rats having initial decreased heart rates followed by a recovery process, while the heart rate responses of BDI rats increased immediately. The novel use of the female Brattleboro rat in this study provides evidence for the existence of an important inhibitory interaction between ovarian steroids and vasopressin during the blood pressure recovery phase following haemorrhage, and indicates a possible direct influence of gonadal steroids on the recovery process.
Assuntos
Pressão Sanguínea , Estro , Hemorragia/fisiopatologia , Ratos Brattleboro/fisiologia , Animais , Diestro , Feminino , Frequência Cardíaca , Hematócrito , Hemorragia/sangue , Masculino , Concentração Osmolar , Proestro , Ratos , Ratos EndogâmicosRESUMO
In addition to the stimulating influence of the sympathetic system on the function of the mammalian pineal gland, neuropeptides such as neuropeptide Y, vasoactive intestinal polypeptide and arginine-vasopressin (AVP) are thought to function as modulators. Since AVP has been shown to influence pineal melatonin synthesis, the aim of the present study was to investigate the possible effects of the second hypothalamic nonapeptide oxytocin (OT), which likewise has been detected in the pineal gland. We therefore studied "synaptic" ribbon (SR) numbers, N-acetyltransferase (NAT) activity and the intracellular concentration of cyclic guanosine monophosphate (cGMP) following in vitro incubation of rat pineals in media containing OT (10(-5) M), noradrenaline (NA, 10(-5) M) or both NA and OT. Pineal glands were derived from rats of three different strains (Sprague-Dawley, Long-Evans and the AVP-deficient strain Brattleboro). Neither morphological nor biochemical analyses showed a difference between control and OT-incubated organs in any of the strains tested. In Brattleboro rats, but not in the other strains, noradrenaline slightly increased the number of SR which was not observed when NA and OT were combined. The addition of NA resulted in distinct augmentation of NAT activity and cGMP content, which were not affected by additional OT application. These results suggest that oxytocin is not crucially involved in the regulation of pineal gland function.
Assuntos
Arilamina N-Acetiltransferase/análise , Ritmo Circadiano/efeitos dos fármacos , GMP Cíclico/análise , Organelas/efeitos dos fármacos , Ocitocina/farmacologia , Glândula Pineal/efeitos dos fármacos , Ratos Brattleboro/fisiologia , Ratos Endogâmicos/fisiologia , Animais , Arginina Vasopressina/deficiência , Comunicação Celular , Masculino , Norepinefrina/farmacologia , Técnicas de Cultura de Órgãos , Organelas/ultraestrutura , Ocitocina/fisiologia , Glândula Pineal/fisiologia , Glândula Pineal/ultraestrutura , Ratos , Ratos Sprague-Dawley/fisiologiaAssuntos
Aprendizagem/fisiologia , Memória/fisiologia , Hormônios Neuro-Hipofisários/fisiologia , Medula Suprarrenal/metabolismo , Amnésia/tratamento farmacológico , Tonsila do Cerebelo/fisiologia , Animais , Aprendizagem da Esquiva/fisiologia , Epinefrina/fisiologia , Hormônios/fisiologia , Ratos , Ratos Brattleboro/fisiologia , Vasopressinas/farmacologia , Vasopressinas/fisiologiaAssuntos
Angiotensina II/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Encéfalo/fisiologia , Ratos Brattleboro/fisiologia , Vasopressinas/farmacologia , Animais , Diabetes Insípido/líquido cefalorraquidiano , Diabetes Insípido/fisiopatologia , Ratos , Ratos Endogâmicos , Valores de Referência , Fatores de Tempo , Vasopressinas/líquido cefalorraquidianoRESUMO
In the present study we examined the influence of arginine vasopressin (AVP) on conditioned freezing behavior to aversive shock treatment by comparing the responses of Brattleboro homozygous (DI) rats, Brattleboro heterozygous (HZ) rats, and Long-Evans (LE) rats. Each animal was placed in a sound-attenuated shock chamber on the training day and given a series of 3 footshocks. On the following 4 consecutive days the rats were placed in the chambers where they had received their shock and levels of spontaneous freezing were evaluated. Levels of circulating vasopressin-associated neurophysin (NP) were subsequently determined in each rat strain. For each of the 4 test days, DI rats displayed significantly less freezing behavior when compared with LE rats and HZ rats. HZ rats displayed trends towards attenuated freezing responses when compared with LE rats. The data indicate that a relationship exists between the levels of central nervous system (CNS) and circulating AVP, and the amount of freezing displayed by each strain. These preliminary results suggest that vasopressin may be involved in appropriate autonomic and emotional responses to fearful stimuli in fear conditioning paradigms.
Assuntos
Condicionamento Psicológico , Medo , Homozigoto , Atividade Motora/fisiologia , Ratos Brattleboro/fisiologia , Animais , Arginina Vasopressina/fisiologia , Aprendizagem da Esquiva , Diabetes Insípido/genética , Eletrochoque , Feminino , Heterozigoto , Masculino , Neurofisinas/sangue , Ratos , Ratos Brattleboro/sangue , Ratos Brattleboro/genética , Ratos EndogâmicosRESUMO
Hypothalamic neurosecretory neurons transcribe, translate, store, and secrete a large number of chemical messengers. The neurons contain hypothalamic signal substances that regulate the secretion of anterior pituitary hormones as well as the neurohypophysial peptides vasopressin and oxytocin. In addition to the classical hypophysiotropic hormones, a large number of neuropeptides and classical transmitters of amine and amino acid nature are present in the same cells. This is particularly evident in the magnocellular neurons of the supraoptic and paraventricular nuclei, and in parvocellular neurons of the arcuate and paraventricular nuclei. The changes in gene expression induced by experimental manipulations and the colocalization chemical messengers in hypothalamic neurosecretory neurons and its possible significance is summarized in this review.
Assuntos
Regulação da Expressão Gênica , Hormônios Hipotalâmicos/genética , Hipotálamo/metabolismo , Neurônios/metabolismo , Neuropeptídeos/genética , Neurotransmissores/biossíntese , Animais , Ácido Aspártico/fisiologia , Glutamatos/fisiologia , Ácido Glutâmico , Humanos , Hipofisectomia , Hormônios Hipotalâmicos/biossíntese , Hormônios Hipotalâmicos/metabolismo , Sistema Hipotálamo-Hipofisário/fisiologia , Hipotálamo/anatomia & histologia , Hipotálamo/citologia , Neuropeptídeos/biossíntese , Neuropeptídeos/metabolismo , Neurotransmissores/metabolismo , Concentração Osmolar , Ratos , Ratos Brattleboro/fisiologia , Glutamato de Sódio/toxicidadeRESUMO
Mice selected for differences in nest-building behavior differ in the number of arginine-vasopressin (AVP)-immunoreactive neurons in the suprachiasmatic nuclei (SCN). Although previous efforts to link AVP-immunoreactive neurons in the SCN to clock function have failed, we show that differences in several circadian parameters are associated with differences in the number of AVP-immunoreactive neurons between the selected lines. Although an alternative interpretation is discussed, we hypothesize that these neurons may relay timing information from the circadian pacemaker in the SCN for wheel-running activity. In addition, phase-response curves (PRCs) to 15-min light pulses in constant darkness also differ between the selected lines. However, these differences are not associated with the number of the AVP-immunoreactive neurons in the SCN, but are associated with the level of nest-building behavior. Compared to the Brattleboro rat, in which homozygous rats are deficient for AVP in the entire brain, our system, exhibiting a wide range of variability, has more specific utility for studying the role of the output pathways of the SCN in circadian rhythm control.
Assuntos
Arginina Vasopressina/fisiologia , Ritmo Circadiano , Camundongos Endogâmicos/fisiologia , Atividade Motora , Neurônios/fisiologia , Núcleo Supraquiasmático/fisiologia , Análise de Variância , Animais , Escuridão , Luz , Camundongos , Ratos , Ratos Brattleboro/fisiologiaRESUMO
Chronic prophylactic exogenous insulin treatment commenced in young diabetes susceptible BB rats has been shown to prevent type I diabetes. This study was undertaken to examine whether this diabetes protection resulted from inhibition of beta-cell insulin secretion by exogenous insulin administration or from either a metabolic (chronic hypoglycemia) or immune effect of this treatment. We compared the effects of prophylactic exogenous insulin treatment with those of an insulin secretion inhibitor, diazoxide, an oral hypoglycemic agent, glyburide, and, water alone as controls in randomly divided BB diabetes-prone littermates treated from age 30 to 150 days. These experiments confirmed that exogenous insulin can prevent type I diabetes in the BB rat. Diazoxide, which inhibits endogenous insulin secretion while causing hyperglycemia (rather than hypoglycemia with insulin), also offered protection from diabetes. In contrast, the oral hypoglycemic agent glyburide, which increased insulin secretion, but decreased plasma glucose during the early part of the experiment, did not affect the incidence of diabetes. The lymphocyte subpopulations were unaffected by these treatments. These data support the hypothesis that decreased beta-cell activity is responsible for the protection against the immune beta-cell destruction.
Assuntos
Diabetes Mellitus/prevenção & controle , Antagonistas da Insulina/farmacologia , Ratos Brattleboro/fisiologia , Análise de Variância , Animais , Glicemia/análise , Diazóxido/farmacologia , Teste de Tolerância a Glucose , Glibureto/farmacologia , Insulina/sangue , Insulina/metabolismo , Insulina/farmacologia , Pâncreas/metabolismo , Pâncreas/patologia , RatosRESUMO
Vasopressin (VP) was administered in the lateral cerebral ventricles of homozygous rats with congenital diabetes insipidus of Brattleboro (BB) strain as well as of normal animals of Long Evans strain (LE). The following parameters were studied: the latent period for achievement of maximal pressor response in seconds (LP), absolute value of the increase in arterial pressure in comparison with the initial V mmHg (delta AP) and cardiac frequency (CF). The initial values of AP in BB were lower than those values found in LE (BB-9, 10 +/- 0.57 kPa; LE-11, 31 +/- 0.53 kPa; p less than 0.01, while CF showed higher values in BB (350 +/- 8.5 min-1); LE (321 +/- 10 min-1); p less than 0.05. VP, administered intraventricularly, induced quick transitory elevation of AP in both groups, which did not differ substantially both in respect to LP (BB-55 +/- 11 s; LE-43 +/- 6.9) and also in respect to delta AP (BB-3.64 +/- 0.34; LE-3.14 +/- 0.62). CF was not changed in BB (347 +/- 8.9), while it was slightly increased in LE (334 +/- 11). The data show that exogenously administered VP affect the central VP-dependent mechanisms for regulation of AP in the same way in both groups of rats.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Ratos Brattleboro/fisiologia , Ratos Endogâmicos/fisiologia , Vasopressinas/administração & dosagem , Animais , Pressão Sanguínea/fisiologia , Diabetes Insípido/fisiopatologia , Frequência Cardíaca/fisiologia , Injeções Intraventriculares , Ratos , Estimulação Química , Vasopressinas/farmacologiaRESUMO
Almitrine bismesylate simulates the effects of arterial hypoxia in producing a specific and long-lasting excitation of the peripheral arterial chemoreceptors. Previous work has shown that almitrine produces a diuresis and natriuresis when given intravenously to anaesthetised rats in a stable mannitol induced diuresis. This response is abolished by glossopharyngeal nerve section implying that it is afferently mediated via the carotid body chemoreceptors. We have studied further the efferent limb of this response. The diuresis and natriuresis occurs without significant detectable changes in effective renal plasma flow and glomerular filtration rate suggesting that it is produced mainly by inhibition of renal tubular sodium and water reabsorption. Almitrine produces a diuresis and natriuresis in rats after bilateral nephrectomy and transplantation of a kidney from a donor rat. This effect is not therefore efferently mediated by the renal nerves and probably involves a humoral agent. Almitrine produces a diuresis and natriuresis in rats after bilateral adrenalectomy and in rats with congenital hypothalamic diabetes insipidus indicating that neither adrenal hormones nor changes in antidiuretic hormone levels are implicated.