Neuron-specific thresholds of aluminum toxicity in vitro. A comparative analysis of dissociated fetal rabbit hippocampal and motor neuron-enriched cultures.
Mature dissociated motor neuron-enriched and hippocampal neuron cultures derived from fetal New Zealand white rabbits were continuously exposed to 1, 10, 25, 50, or 100 microM AlCl3 in a chemically defined medium for 14 days. Motor neuron-enriched cultures exposed to low concentrations (1 or 10 microM) of AlCl3 remained viable for the entire experiment but developed perikaryal and neuritic inclusions composed of phosphorylated neurofilament. Similar inclusions developed in cultures exposed to 25 and 50 microM AlCl3, but motor neurons did not survive beyond 10 days exposure. The 100 microM AlCl3-supplemented medium induced cell death within 72 hours without development of inclusions. In contrast, hippocampal neurons exposed to 1, 10, or 25 microM AlCl3 developed no morphological changes or inclusions. Although hippocampal cultures exposed to 50 or 100 microM AlCl3 developed perinuclear and proximal neuritic inclusions of phosphorylated neurofilament after 10 days, they remained viable. These in vitro morphological observations demonstrate a 10-fold greater sensitivity of spinal motor neurons to aluminum toxicity when compared with hippocampal neurons and suggest that the earlier observations of neuron-specific thresholds of aluminum toxicity in vivo are related to unique regulatory mechanisms of neurofilament biosynthesis and catabolism within distinct neuronal cell populations.
Strong
M J
MJ
Department of Clinical Neurological Sciences, University of Western Ontario, London, Canada.
Garruto
R M
RM
D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D005333:Fetus / Q000166:cytology; D006624:Hippocampus / Q000166:cytology* / Q000196:embryology; D007150:Immunohistochemistry; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D011817:Rabbits; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology
D000535:Aluminum