Neurotoxic effect induced by quinolinic acid in dissociated cell culture of mouse hippocampus

Abstract

Quinolinic acid (QUIN), an endogenous convulsant that is a product of tryptophan metabolism, is suggested to belong to the pathogenic factors in some neurodegenerative disorders of the central nervous system (CNS). The aim of the present study was to evaluate the effect of QUIN on hippocampal nerve cells in dissociated cell culture at different periods of its development in vitro. The neurodegenerative effect of QUIN in vitro was found 1.5 to 2 hr after exposure to QUIN (500 microM) in differentiated hippocampal culture 20-21 days in vitro (DIV). The cytotoxic action depended on the nature of the interneuronal relations established in culture and on the period of neuronal development in vitro. Neurons in 11-DIV cultures were undamaged even 10 days after exposure to QUIN; nor were the individual, isolated neurons probably not connected synaptically with the other ones in 20-21 DIV cultures. Ultrastructural analysis of 20-21 DIV cultures exposed to QUIN showed acute swelling and destruction of postsynaptic elements and severe degeneration of individual nerve cells located in cellular aggregates, whereas presynaptic axon terminals remained intact. The results emphasize the utility of QUIN as a tool to model degenerative changes of CNS and confirm the participation of mature synaptic junctions in QUIN neurotoxicity.

Somatic Drugs for Psychiatric Diseases: Aspirin or Simvastatin for Depression?

“…Some TRYCATs, such as quinolinic acid and kynurenine, are extremely neurotoxic [127, 128], as quinolinic acid causes acute tumefaction and the destruction of post-synaptic elements, induces nerve cell degeneration, including hippocampal cell death and selective necrosis of granular cells, among others. Quinolinic acid causes a dose-dependent decrease in cholinergic circuits and may empty dopamine, choline, GABA and encephalin deposits [129-133]. The areas most affected by the neurotoxic effects of quinolinic acid would be the striatum, the pallidal formation and the hippocampus [134].…”

Hypoxic and Posthypoxic Neuronal Injury in Hippocampal Cell Culture: Attenuation by Lipophylic Antioxidant U-18 and Superoxide Dismutase

“…Hippocampal cell cultures were prepared from fetal mice C57 Black at 17-19 days gestation as previously described (Khaspekov, Kida, Victorov & Mossakowski, 1989). Briefly, trypsin dissociated hippocampal cells were resuspended in nutrient medium (Eagle's minimal essential medium supplemented with 5% fetal bovine serum, 5% human placentar serum, 600 mg/% glucose, 0.2 U/ml insulin, 2 mM glutamine and 10 mM HEPES) and plated on 22 x 22 mm glass coverslips (about 2.0-2.5 x 105 cells in 150 p1 of suspension per coverslip), coated, by modified Hawrot's method (Hawrot, 1980), with bilayer supporting substratum, consisting of collagen and covalently bounded poly-L-lysine.…”

Dramatic effects of external alkalinity on neuronal calcium recovery following a short‐duration glutamate challenge: the role of the plasma membrane Ca2+/H+ pump

“…The hippocampi from C57/Bl mouse embryos of 17-19 day gestatIOnal age were dissected. dissociated and cultivated as prevIOusly descnbed [6]. The expenments With cultured hippocampal neurons were performed on days 18-22 of cultivatIOn.…”