Differential vulnerabilities of substantia nigra catecholamine neurons to excitatory amino acid-induced degeneration in rat midbrain slices

Although differential vulnerability in different regions of the central ner vous system is a characteristic feature of neurodegenerative disorders in v ivo its cellular basis is not well understood In the present study ave inve stigated whether catecholamine neurons in. different regions of the substan tia nigra (SN) are differentially vulnerable to excitatory amino acid-induc ed damage in a midbrain slice preparation. Rats were anesthetized by haloth ane inhalation and killed, the brain was rapidly removed, and 300-mu m-thic k mid-brain slices were cut horizontally on at vibratome. The slices were i ncubated at 35 degrees C: for 2 h in saline buffer containing either kainic acid (RA) or N-methyl-D-aspartate (NMDA) (10-50 mu M). They were then fixe d and cut into 30-mu m sections that were coplanar with the horizontal slic e. Individual catecholamine neurons were identified in these thin sections using an antibody to tyrosine hydroxylase coupled to diaminobenzidine. Cate cholaminergic neurons in the dorsal and ventral tiers of the SN were readil y identified by reference to an atlas of the distribution of catecholamine neurons in the horizontal plane. Using dendritic degeneration as a sensitiv e index of damage, and submaximal concentrations of KA and NMDA, we found t hat catecholamine neurons in the dorsal tier were more vulnerable than thos e in the ventral tier. For example, KA (10 mu M) caused a significant reduc tion in the proportion of neurons with dendrites in the dorsal tier (from 6 0 to 34%) without altering the dendritic arbor of ventral tier neurons, Aft er treatment with 50 mu M KA, only 11% of dorsal tier neurons retained any dendrites while 45% of ventral tier neurons retained their dendrites, These differences were statistically significant (P < 0.001). A similar differen tial vulnerability was apparent in slices treated with NMDA; neurons in the dorsal tier lost dendrites before detectable damage in the ventral tier. A n understanding of the comparative anatomical, neurochemical, and physicolo gical properties of vulnerable (dorsal tier) and resistant (ventral tier) c atecholamine neurons in rat SN may provide significant insights into the me chanisms and treatment of neurodegenerative disorders involving catecholami ne neurons. (C) 2000 Academic Press.