Melatonin ameliorates neocortical neuronal dendritic impairment induced by toluene inhalation in the rat

Solvent inhalation (toluene and n‐hexane) during the brain growth spurt impairs the maturation of frontal, parietal and occipital cerebrocortical neurons in rats

“…The present study showed that the inhalation of volatile solvents during the first 3 postnatal weeks causes cortical cell impairments that are more dramatic than those observed in postweaning "sniffer" rats. For example, in animals exposed the toluene fumes between P21 and P31, the mean number of dendritic branches/neuron was reduced ∼30% (Pascual et al, 2010); in the present study, however, dendritic branching was reduced ∼50% relative to age-matched control rats. Although the studies are not entirely comparable, the increased neurotoxic effect of solvent inhalation in weanling rats could be partially explained by the higher rate of dendritic outgrowth that occurs during this critical ontogenetic stage (Chien et al, 2005;Miller, 1981;Takashima et al, 1980).…”

“…but also reduces the expression of enzymes that counteract oxidative stress (i.e., glutathione peroxidase, catalase and reductase; Edelfors et al, 2002). The oxidative stress hypothesis is supported by studies showing that the administration of antioxidants such as melatonin can counter the neurotoxic effects of toluene (Baydas et al, 2003;Pascual et al, 2010). In addition, because glutamatergic NMDA receptors play an important role in neural development and plasticity (Cull-Candy et al, 2001) and because toluene administered during the preweaning period significantly altered NMDA receptor expression and function (Chen et al, 2005;Chien et al, 2005;Lee et al, 2005), it is possible that NMDA dysfunction may significantly contribute to the structural cell impairments observed in this and previous developmental studies.…”

“…This is the first study to assess the impact of organic solvents on neocortical pyramidal cells during the brain growth spurt in rats. In our previous studies, we demonstrated that toluene exposure during the early postweaning period (P22–P32) can alter dendritic outgrowth and branching in layer II/III pyramidal cells (Pascual et al, 2010). The present study showed that the inhalation of volatile solvents during the first 3 postnatal weeks causes cortical cell impairments that are more dramatic than those observed in postweaning “sniffer” rats.…”

“…In previous studies, we have demonstrated that weanling rats exposed to a mixture of solvent vapors commonly found in glues (75% toluene and 18% n ‐hexane) displayed significant morphological impairments in cerebellar Purkinje cells (Pascual et al, 1996). In addition, the neocortical pyramidal cells of postweaning rats exposed to toluene vapors exhibited significantly impaired dendritic branching relative to age‐matched control animals (Pascual et al, 2010). However, no previous studies have investigated the effect of solvent inhalation on cerebrocortical dendritic development during the brain growth spurt.…”

Persistent cognitive and morphological alterations induced by repeated exposure of adolescent rats to the abused inhalant toluene

“…Chronic toluene exposure has been reported to decrease dendritic complexity in superficial cortical layers following 48 h of abstinence (Pascual et al, 2011; Pascual & Bustamante, 2010, 2011). The present findings add to these data by showing that protracted abstinence from toluene exposure (7 weeks) is associated with increases in long-thin spines in the NAc.…”