Protective role of noradrenaline in benzo[a]pyrene-induced learning impairment in developing rat
- 30 August 2013
- journal article
- research article
- Published by Wiley in Journal of Neuroscience Research
- Vol. 91 (11), 1450-1462
- https://doi.org/10.1002/jnr.23265
Abstract
Benzo[a]pyrene (B[a]P), a carcinogen, affects brain development, learning, and memory. Isolated studies have reported that B[a]P elevates noradrenaline (NA) level that may modulate neuronal growth, learning, and memory. Therefore, we investigated in vivo and in vitro the effects of B[a]P on learning and memory and its possible mechanism of action. Intracisternal administration of B[a]P on postnatal day 5 significantly reduced learning and memory in adolescent rats as observed by probe test using the Morris water maze. The density of both the subunits of the N‐methyl‐D‐aspartate (NMDA) receptor, NMDAR1 and NMDAR2B, significantly increased in the hippocampus. In vitro, B[a]P significantly increased NMDAR1 in both C6 and Neuro2a cell lines, whereas NMDAR2B was significantly increased in C6 but was significantly decreased in Neuro2a. Pretreatment with NA prevented the B[a]P‐induced effect on NMDAR1 expression in both cell lines. However, although NA prevented the B[a]P‐mediated increase in NMDAR2B expression in C6, it further potentiated the decrease of NMDAR2B in Neuro2a cells. Also, NA prevented the B[a]P‐induced increase in intracellular Ca2+ both in C6 and in Neuro2a. Our findings show that postnatal exposure of developing rats to B[a]P impairs learning and memory even when the rats became adolescent. We also observed that the effects were mediated by elevated intracellular Ca2+ levels and increased expression of NMDAR; furthermore, NA exerted a protective effect by modulating those factors. NA differentially affects neurons and glia, which may have a compensatory role during toxic insults, especially from B[a]P.Keywords
This publication has 51 references indexed in Scilit:
- Early Postnatal Benzo(a)pyrene Exposure in Sprague-Dawley Rats Causes Persistent Neurobehavioral Impairments that Emerge Postnatally and Continue into Adolescence and AdulthoodToxicological Sciences, 2011
- Effects of lactational exposure to benzo[α]pyrene (B[α]P) on postnatal neurodevelopment, neuronal receptor gene expression and behaviour in miceToxicology, 2009
- Understanding memory through hippocampal remappingTrends in Neurosciences, 2008
- Stimulatory role of calcium in rapid eye movement sleep deprivation–induced noradrenaline-mediated increase in Na-K-ATPase activity in rat brainNeuroscience, 2008
- Down-regulation of early ionotrophic glutamate receptor subunit developmental expression as a mechanism for observed plasticity deficits following gestational exposure to benzo(a)pyreneNeuroToxicology, 2007
- The hippocampus, space, and viewpoints in episodic memoryThe Quarterly Journal of Experimental Psychology Section A, 2002
- NMDA receptor subunits: diversity, development and diseaseCurrent Opinion in Neurobiology, 2001
- A synaptic model of memory: long-term potentiation in the hippocampusNature, 1993
- Calcium-mediated neurotoxicity: relationship to specific channel types and role in ischemic damageTrends in Neurosciences, 1988
- Developmental characteristics of brain catecholamines and tyrosine hydroxylase in the rat: effects of 6‐hydroxydopamineBritish Journal of Pharmacology, 1972