RESUMO
Neuroprotective effects of short prolactin (PRL) pre-treatment against kainic acid (KA)-induced damage include neuron loss avoidance in all hippocampal regions and attenuation of seizures. Recent evidence points PRL receptor (PRL-R) as mediator of such neuroprotective effects and seizures as regulators of neuronal marker transcript expression in the hippocampus. Here, we investigated if a daily PRL dose of 100 µg or vehicle for 14 days in ovariectomized rats (OVX) prevents neuron loss induced by KA administered on the third day of PRL treatment in a systemic single dose of 7.5 mg/kg or vehicle, and promotes PRL-R, vesicular glutamate transporter 1 (VGLUT1) and glutamic acid decarboxylase 65 (GAD65) expression changes in the hippocampus of sacrificed rats 27 days after the KA administration. Immunostaining for Neu-N and PRL-R revealed significant neuron number and PRL-R expression reduction induced by KA that was prevented and turned into overexpression respectively in all hippocampal regions when PRL was added; while VGLUT1,and GAD65 immunostaining displayed expression decrease in the CA1 of injured rats, prevented in the last case and turned into VGLUT1, overexpression when administered PRL. These data indicate that chronic PRL administration before damage induces hippocampal neuroprotection associated with PRL-R and VGLUT1 overexpression, the latter in a regiondependent way.
Assuntos
Hipocampo/efeitos dos fármacos , Ácido Caínico/toxicidade , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Prolactina/administração & dosagem , Receptores da Prolactina/metabolismo , Proteína Vesicular 1 de Transporte de Glutamato/metabolismo , Animais , Agonistas de Aminoácidos Excitatórios/toxicidade , Feminino , Glutamato Descarboxilase/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Neurônios/metabolismo , RatosRESUMO
Cryptorchidism is a frequent genitourinary malformation considered as an important risk factor for infertility and testicular malignancy. The aetiology of cryptorchidism is multifactorial in which certain SNPs, capable of inhibiting the development of the gubernaculum, are implicated. We analysed 16 SNPs by allelic discrimination and automated sequencing in 85 patients and 99 healthy people, with the objective to identify the association between these variants and isolated cryptorchidism. In two different patients with unilateral cryptorchidism, we found the variants rs121912556 and p.R105R of INSL3 gene in a heterozygous form associated with cryptorchidism, so we could considered them as risk factors for cryptorchidism. On the other hand, SNPs rs10421916 of INSL3 gene, as well as the variants rs1555633 and rs7325513 in the RXFP2 gene, and rs3779456 variant of the HOXA10 gene were statistically significant, when the patients and controls were compared and could be considered as protective factors since are predominantly present in controls. The genotype-phenotype correlation did not show statistical significance. With these results, we could conclude that these polymorphisms can be considered as important variants in our population and would contribute in the future knowledge of the aetiology and physiopathology of cryptorchidism.
Assuntos
Criptorquidismo/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Adolescente , Alelos , Criança , Pré-Escolar , Estudos de Associação Genética , Haplótipos , Proteínas Homeobox A10 , Proteínas de Homeodomínio/genética , Humanos , Lactente , Insulina/sangue , Insulina/genética , Desequilíbrio de Ligação , Masculino , México , Proteínas/genética , Receptores Acoplados a Proteínas G/genéticaRESUMO
Pyrimethamine (PYR) is a drug used in the treatment of newborn with congenital Toxoplasmosis. Even when PYR is highly specific against parasites, it may provoke neutropenia in the patients apart from other affectations, conditions that usually justify its suspension. Moreover, medication against congenital toxoplasmosis coincides with the proliferation stage of Sertoli and germ cells. Although, there are several reports on the effect of this drug on mature testes, records of its effects on the testes of young individuals yet in the process of growth are still lacking. This work was aimed to study the effects of in vivo administration of PYR in the first 21 days of life of male rat pups by evaluating their testicular alterations and its long-term sequels on fertility. Through the determination of the levels of seminiferous epithelium maturity, apoptotic index and cell proliferation index at 7, 14, 35 and 90 days post-natal using immunocytochemical studies. The fertility of the treated rats was evaluated at 90 days. PYR-treated animals were found to undergo some kind of delays in seminiferous epithelium maturity, decreased cell proliferation index and an increase in apoptosis when compared with the control (p < 0.05). Epididymal sperm counts were also affected (p < 0.05). The application of folic acid (FA) in newborns treated with PYR decreased the severity of the problem (p < 0.05). This study provides strong evidence that the effect of PYR on testicular development is specific. It reinforces the importance of FA application in neonates treated with PYR to prevent the effect of the later on spermatogenesis.
Assuntos
Fertilidade/efeitos dos fármacos , Antagonistas do Ácido Fólico/efeitos adversos , Pirimetamina/efeitos adversos , Epitélio Seminífero/efeitos dos fármacos , Testículo/patologia , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ácido Fólico/farmacologia , Antagonistas do Ácido Fólico/farmacologia , Masculino , Pirimetamina/farmacologia , Ratos , Ratos Wistar , Células de Sertoli/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Testículo/citologia , Toxoplasmose/tratamento farmacológicoRESUMO
UNLABELLED: The small intestine of the rat shows morphologic and enzymatic changes that are associated with the weaning and may be alternated by the early weaning, however, the morphometric criteria have been disregarded. MATERIAL AND METHODS: In this study, the effects of precocious weaning (15 days) and prolonged weaning (32 days), on the size and number of villi; and crypts of small intestine, were analyzed in rats from 16 to 70 days of age. RESULTS: Precocious weaning increased the size of villi, depth and number of crypts in the duodenum and jejunum, while the number of villi decreased. Pups nursed up to 32 days showed no alterations in the analyzed parameters. However, the ileum showed no alterations with the precocious weaning or prolonged. CONCLUSIONS: These data support the concept of an intrinsic biologic program as control of intestinal development while the change of diet seem to have a modifying role in duodenum and jejunum.