Neuroscience
-
Bisphenol-A (BPA), one of the most common environmental endocrine disrupters, has been extensively evaluated for toxicity in a variety of tests in rodents, including developmental and reproductive toxicity, and carcinogenicity. However, little is known about its action on the CNS. In this report, we show that prenatal and neonatal exposure to BPA in mice leads to the enhancement of the dopamine D1 receptor-dependent rewarding effect induced by a psychostimulant methamphetamine. ⋯ Additionally, chronic BPA exposure produced a significant increase in levels of the dopamine D1 receptor mRNA in the whole brain. In contrast, no change in protein levels of methamphetamine-targeted proteins, dopamine transporter or the type 2 vesicle monoamine transporter in the brain was observed by prenatal and neonatal exposure to BPA. The present data provide the first evidence that prenatal and neonatal exposure to BPA can potentiate the central dopamine D1 receptor-dependent neurotransmission, resulting in supersensitivity of methamphetamine-induced pharmacological actions related to psychological dependence on psychostimulants.
-
The neural cell adhesion molecule (NCAM) plays a key role in synaptic plasticity and memory formation. We have recently developed a synthetic peptide, termed C3d, which, through the binding to the first, N-terminal immunoglobulin-like (Ig) module in the extracellular portion of NCAM, has been shown to promote neurite outgrowth and synapse formation in vitro, and to interfere with passive avoidance memory in rats in vivo. In this study, we investigated whether the i.c.v. administration of C3d, either 5.5 h after or 2 days before training, could be effective to modulate the strength at which emotional memory for aversive situations is established into a long-term memory. ⋯ Furthermore, hippocampal levels of microtubule-associated protein 2 (MAP2), Synaptophysin and NCAM were found unchanged when evaluated by enzyme-linked immunosorbent assay in crude synaptosomal preparations 2 days after peptide i.c.v. injection. Therefore, post-training injection of this synthetic peptide was efficient to attenuate the strength at which memory for contextual fear conditioning was enduringly stored, whilst it did not affect the acquisition of new memories. In addition to further support the view that NCAM is critically involved in memory consolidation, the current findings suggest that the NCAM IgI module is a potential target for the development of therapeutic drugs capable to reduce the cognitive impact induced by exposure to intensive stress experiences.
-
N-Acetyl-L-aspartyl-L-glutamate (NAAG) is one of the most abundant neuroactive compounds in the mammalian CNS. Our recent observations have suggested that NAAG administered into rat cerebral ventricles can cause neuronal death by apparently excitotoxic mechanisms that can be antagonized by the N-methyl-D-aspartate-receptor blockers and by ligands of metabotropic glutamate receptor of Group II. Therefore, the principal aim of the present study has been to use quantitative morphology, electron microscopy and terminal deoxynucleotidyl transferase-mediated biotin dUTP nick-end labeling to study a dose- and time-dependence as well as regional distribution of neurodegeneration in hippocampi of rats after the intraventricular infusion of 0.25 micromol NAAG/ventricle and of equimolar doses of L-glutamate (L-GLU) and N-acetyl-L-aspartate (NAA), breakdown products of NAAG. ⋯ The degeneration was characterized on the basis of ultrastructural appearance and DNA-fragmentation. The morphological changes caused by L-glutamate and NAA were much smaller than those observed after the administration of NAAG and displayed a different pattern of regional distribution. The present findings suggest that NAAG can cause a loss of hippocampal neurons in vivo, apparently resulting from the neurotoxicity of NAAG itself.
-
The distribution of N-methyl-D-aspartate- (NMDA) and kainic acid- (KA) sensitive ionotropic glutamate receptors (iGluR) in the zebrafish olfactory bulb was assessed using an activity-dependent labeling method. Olfactory bulbs were incubated with an ion channel permeant probe, agmatine (AGB), and iGluR agonists in vitro, and the labeled neurons containing AGB were visualized immunocytochemically. Preparations exposed to 250 microM KA in the presence of a NMDA receptor antagonist (D-2-amino-5-phosphono-valeric acid) and an alpha-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist (sym 2206), revealed KA receptor-mediated labeling of approximately 60-70% of mitral cells, juxtaglomerular cells, tyrosine hydroxylase-positive cells and granule cells. ⋯ Application of 333 microM NMDA in the presence of an AMPA/KA receptor antagonist (6-cyano-7-nitroquinoxaline-2,3-dione) resulted in NMDA receptor-mediated labeling of almost all neurons. The concentrations eliciting 50% of the maximal response (effective concentration: EC(50)s) for NMDA-stimulated labeling of different cell types were not significantly different and ranged from 148 microM to 162 microM. These results suggest that while NMDA receptors with similar binding affinities are widely distributed in the neurons of the zebrafish olfactory bulb, KA receptors are heterogeneously expressed among these cells and may serve unique roles in different regions of the olfactory bulb.
-
Since metabolic neural activity is accompanied by heat release, measurement of local brain temperature offers a method for assessing alterations in neural activity. This approach, continuous monitoring of local brain (ventral tegmental area, ventral striatum, and hippocampus) and body (temporal muscle) temperature, was used to study intravenous cocaine self-administration in trained rats. The first self-administration of a session was preceded by a strong temperature increase that continued after the drug infusion. ⋯ These data suggest a generalized brain activation associated with cocaine-seeking and cocaine-taking behavior with its phasic fluctuations around individual drug self-injections. While the initial component of brain activation preceding the first lever-press for cocaine is internally determined and closely related to behavioral search, subsequent biphasic fluctuations in neural activity associated with repeated drug intakes appear to be drug-mediated. Cocaine-induced potentiation of monoamine transmission is a possible factor for gradual increases in neural activity that drive cocaine seeking, while a rapid, brain concentration-dependent action on Na(+) transport (local anesthetic action) is the most probable factor determining an abrupt, transient cessation of neural activation associated with cocaine reward.