Toluene disrupts synaptogenesis in cultured hippocampal neurons.
Prenatal toluene exposure may lead to significant developmental neurotoxicity known as fetal solvent syndrome. Emerging evidence suggests that toluene embryopathy may arise from an elusive deviation of the neurogenesis process. One key event during neural development is synaptogenesis, which is essential for the progression of neuronal differentiation and the establishment of neuronal network. We therefore aim to test the hypothesis that toluene may interfere with synaptogenesis by applying toluene to cultured hippocampal neurons dissected from embryonic rat brains. In the presence of toluene, hippocampal neurons displayed a significant loss of the immunostaining of synapsin and densin-180 punctas. Notably, a dramatic reduction was also discerned for the colocalization of the two synaptic markers. Moreover, Western blotting analyses revealed that toluene exposure resulted in considerable down-regulation of the expression of synapse-specific proteins. None of the preceding observations can be attributed to toluene-induced cell death effects, since toluene treatments failed to affect the viability of hippocampal neurons. Overall, our data are consistent with the idea that toluene may alter the expression and localization of essential synaptic proteins, thereby leading to a disruption of synapse formation and maintenance.
Lin
Huei-Min
HM
Department of Physiology, National Taiwan University, Taipei, Taiwan.
Liu
Chih-Yang
CY
Jow
Guey-Mei
GM
Tang
Chih-Yung
CY
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000196:embryology; D015151:Immunoblotting; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000378:metabolism; D012997:Solvents / Q000633:toxicity*; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism; D016704:Synapsins / Q000378:metabolism; D014050:Toluene / Q000633:toxicity*
C504463:Lrrc7 protein, rat; D012795:Sialoglycoproteins; D012997:Solvents; D016704:Synapsins; D014050:Toluene