Ultrastructural localization of nitrotyrosine within the caudate-putamen nucleus and the globus pallidus of normal rat brain

Nitration of protein tyrosine residues by nitric oxide (NO) derived reactiv e species results in the production of stable nitrotyrosine (NT) moieties t hat are immunochemically detectable in many regions of normal brain and enr iched in those areas containing constitutive nitric oxide synthase (cNOS). These include the caudate-putamen nucleus (CPN) and the globus pallidus, wh ich receives major inhibitory input from the CPN. To determine the function al sites for NT production in these critical motor nuclei, we examined the electron microscopic immunocytochemical localization of NT and cNOS in rat brain. In the CPN, NT was localized to the somata and dendrites of cNOS-con taining interneurons and spiny neurons, some of which received input from c NOS-labeled terminals. The NT immunoreactivity was most prevalent on outer mitochondrial membranes and nearby segments of the plasma membranes in dend rites and within asymmetric synapses on dendritic spines. In the CPN and gl obus pallidus, there was also a prominent labeling of NT in astrocytic proc esses, small axons, and tubulovesicles and/or synaptic vesicles in axon ter minals. These terminals formed mainly asymmetric synapses in the CPN and in hibitory-type synapses in the globus pallidus where they often apposed cNOS -containing terminals that also formed asymmetric, excitatory-type synapses . Our results suggest that NT is generated by mechanisms requiring the dual actions of excitatory transmitters and NO derived either from interneurons in the CPN or from excitatory afferents in the globus pallidus. The findin gs also implicate NT in the physiological actions of NO within the striatal circuitry and, particularly, in striatopallidal neurons severely affected in Huntington's disease.