Catecholamine neuron groups in rat brain slices differ in their susceptibility to excitatory amino acid induced dendritic degeneration.

Abstract

We investigated whether specific types of catecholamine neurons were differentially vulnerable to damage induced by excitatory amino acids (EAAs) in vitro in a rat brain slice preparation. Brain slices, 300 micro m thick, were cut horizontally, exposed to either N-methyl-D-aspartate (NMDA) or kainic acid (KA) for 2h, fixed and then cut into thin (30 micro m) sections in the same (horizontal) plane as the slice. The sections were immunolabelled for tyrosine hydroxylase to identify different groups of catecholamine neurons (substantia nigra (SN), paranigral (PN), interfascicular (IF) and hypothalamic A11, A13 and A14) which exhibited prominent dendritic projections in the horizontal plane. Loss of dendrites was used as a sensitive index of damage that precedes the loss of the cell body. Catecholamine neurons differed strikingly in their vulnerability of EAA-induced dendrite degeneration. The most vulnerable were those in the dorsal tier of the SN, whereas the most resistant were those in the hypothalamic A11 group. For example, in the dorsal tier of SN, NMDA (50 micro M) reduced the proportion of neurons with dendrites from 64% (+/- 8% SEM) in controls to 13% (+/- 7%) whereas the majority of A11 neurons (69 +/- 10%) retained their dendrites compared to controls (89% +/- 8%). The other groups of catecholamine neurons exhibited intermediate vulnerability. An essentially similar pattern of differential vulnerability was observed with KA. An understanding of the cellular mechanisms that underlie the particular vulnerability of SN neurons in the slice will aid the discovery of pharmacological therapies to prevent or slow the pathological process in neurodegenerative diseases which involve these neurons.