Reduced size of the dendritic tree does not protect Purkinje cells from excitotoxic death.
Purkinje cell loss by excitotoxic damage is a typical finding in many cerebellar diseases. One important aspect of this high sensitivity of Purkinje cells to excitotoxic death might be the enormous size of their dendritic tree, with a high load of excitatory glutamate receptors. We have studied whether reduction in the size of the dendritic tree might confer resistance against excitotoxic death to Purkinje cells. We have grown Purkinje cells in organotypic cerebellar slice cultures under chronic activation of metabotropic glutamate receptors or of protein kinase C. Both treatments strongly reduced dendritic tree size. After this treatment, cells were exposed to the glutamate receptor agonist AMPA, which has a strong excitotoxic effect on Purkinje cells. We found that Purkinje cells with small dendritic trees were as sensitive to AMPA exposure as untreated control cells with large dendritic trees. Immunostaining against vesicular glutamate transporter 1 revealed that the small dendritic trees were densely covered by glutamatergic terminals. Our results indicate that the expansion of the dendritic tree and the total number of AMPA receptors per neuron do not play a major role in determining the susceptibility of Purkinje cells to excitotoxic death.
Anatomical Institute, Department of Biomedicine, University of Basel, Basel, Switzerland.
Olivia S
OS
Gugger
Josef P
JP
Kapfhammer
D000818:Animals; D000831:Animals, Newborn; D064026:Calbindins; D016923:Cell Death / Q000187:drug effects; D002531:Cerebellum / Q000166:cytology; D003712:Dendrites / Q000187:drug effects / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D066298:In Vitro Techniques; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D011689:Purkinje Cells / Q000166:cytology* / Q000187:drug effects*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013569:Synapses / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000633:toxicity*
D064026:Calbindins; D018690:Excitatory Amino Acid Agonists; D064030:S100 Calcium Binding Protein G; C493477:Slc17a6 protein, mouse; D050599:Vesicular Glutamate Transport Protein 2; D008734:Methoxyhydroxyphenylglycol; C020922:4-O-methyl-12-O-tetradecanoylphorbol 13-acetate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D013755:Tetradecanoylphorbol Acetate; C010117:3,4-dihydroxyphenylglycol