RESUMO
Nucleotides and nucleosides play an important role in neurodevelopment acting through specific receptors. Ectonucleotidases are the major enzymes involved in controlling the availability of purinergic receptors ligands. ATP is co-released with several neurotransmitters and is the most important source of extracellular adenosine by catabolism exerted by ectonucleotidases. The main ectonucleotidases are named NTPDases (1-8) and 5'-nucleotidase. Adenosine is a powerful modulator of neurotransmitter release. Caffeine blocks adenosine receptor activity as well as adenosine-mediated neuromodulation. Considering the susceptibility of the immature brain to caffeine and the need for correct purinergic signaling during fetal development, we have analyzed the effects of caffeine exposure during gestational and lactational periods on nucleotide degradation and ectonucleotidase expression from the hippocampi of 7-, 14- and 21-days-old rats. Nucleotides hydrolysis was assessed by colorimetric determination of inorganic phosphate released. Ectonucleotidases expression was performed by RT-PCR. ATP and ADP hydrolysis displayed parallel age-dependent decreases in both control and caffeine-treated groups. AMP hydrolysis increased with caffeine treatment in 7-days-old rats (75%); although there was no significant difference in AMP hydrolysis between control (non caffeine-treated) rats and 14- or 21-days caffeine-treated rats. ADP hydrolysis was not affected by caffeine treatment. Caffeine treatment in 7- and 14-days-old rats decreased ATP hydrolysis when compared to the control group (19% and 60% decrease, respectively), but 21-days-treated rats showed an increase in ATP hydrolysis (39%). Expression levels of NTPDase 1 and 5 decreased in hippocampi of caffeine-treated rats. The expression of 5'-nucleotidase was not affected after caffeine exposure. The changes observed in nucleotide hydrolysis and ectonucleotidases expression could promote subtle effects on normal neural development considering the neuromodulatory role of adenosine.
Assuntos
Cafeína/administração & dosagem , Hipocampo/metabolismo , Nucleotidases/metabolismo , Nucleotídeos/metabolismo , Animais , Animais Recém-Nascidos , Sequência de Bases , Primers do DNA , Feminino , Hipocampo/enzimologia , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Pollution is a world problem with immeasurable consequences. Heavy metal compounds are frequently found as components of anthropogenic pollution. Here we evaluated the effects of the treatment with cadmium acetate, lead acetate, mercury chloride, and zinc chloride in acetylcholinesterase activity and gene expression pattern, as well as the effects of these treatments in antioxidant competence in the brain of an aquatic and well-established organism for toxicological analysis, zebrafish (Danio rerio, Cyprinidae). Mercury chloride and lead acetate promoted a significant decrease in acetylcholinesterase activity whereas they did not alter the gene expression pattern. In addition, the antioxidant competence was decreased after exposure to mercury chloride. The data presented here allowed us to hypothesize a signal transmission impairment, through alterations in cholinergic transmission, and also in the antioxidant competence of zebrafish brain tissue as some of the several effects elicited by these pollutants.
Assuntos
Acetilcolinesterase/metabolismo , Antioxidantes/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Exposição Ambiental/efeitos adversos , Metais Pesados/toxicidade , Animais , Encéfalo/metabolismo , Inibidores da Colinesterase/administração & dosagem , Inibidores da Colinesterase/toxicidade , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Feminino , Masculino , Metais Pesados/administração & dosagem , Peixe-ZebraRESUMO
Demographic aging gives rise to a growing population with age-associated behavioral and cognitive deficits that may be associated at least partially to the increasing prevalence of neurodegenerative disorders, such as Alzheimer's disease (AD). In this disease, it has been observed a decrease in the cholinergic system, which is crucial to memory formation. Scopolamine-induced amnesic effect, through the disruption of the cholinergic neurotransmission, is one of the approaches used to investigate the mechanisms involved in cognitive impairment observed in AD. The aim of our study was to investigate the potential protective role of quercetin and rutin against scopolamine-induced inhibitory avoidance memory deficits in zebrafish. Scopolamine (200 µM dissolved in the tank water for 1h) given pre-training hindered memory formation while both quercetin and rutin pretreatments (50mg/kg, single injection, i.p.) prevented the scopolamine-induced amnesia. None of the compounds affected zebrafish general locomotor activity. Together, these results contribute to the increase of the knowledge about plant compounds applicability as medicines to prevent and treat neurodegenerative diseases, like Alzheimer's disease.