Protective role of noradrenaline in benzo[a]pyrene-induced learning impairment in developing rat

Patri, Manorama ; Singh, Abhishek ; Mallick, Birendra Nath (2013) Protective role of noradrenaline in benzo[a]pyrene-induced learning impairment in developing rat Journal of Neuroscience Research, 91 (11). pp. 1450-1462. ISSN 0360-4012

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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.

Item Type:Article
Source:Copyright of this article belongs to John Wiley and Sons.
Keywords:Brain Development; Calcium; Carcinogen; Intracisternal Injection; Neuron–glia Interaction; Neurotoxicity; NMDA Receptor Subunits
ID Code:99376
Deposited On:21 Apr 2016 08:06
Last Modified:21 Apr 2016 08:06

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