DISTRIBUTION OF NEURONAL APOPTOSIS INHIBITORY PROTEIN-LIKE IMMUNOREACTIVITY IN THE RAT CENTRAL-NERVOUS-SYSTEM

We have recently shown that spinal muscular atrophy (SMA), an autosoma l recessive disorder characterized by motor neuron loss, is associated with deletion of a gene that encodes the neuronal apoptosis inhibitor y protein (NAIP). In the present study, we have examined the distribut ion of NAIP-like immunoreactivity (NAIP-LI) in the rat central nervous system (CNS) by using an affinity-purified polyclonal antibody agains t NAIP. In the forebrain, immunoreactive neurons were detected in the cortex, the hippocampus (pyramidal cells, dentate granule cells, and i nterneurons), the striatum (cholinergic interneurons), the basal foreb rain (ventral pallidum, medial septal nucleus, and diagonal band), the thalamus (lateral and ventral nuclei), the habenula, the globus palli dus, and the entopenduncular nucleus. In the midbrain, NAIP-LI was loc ated primarily within neurons of the red nucleus, the substantia nigra pars compacta, the oculomotor nucleus, and the trochlear nucleus. In the brainstem, neurons containing NAIP-LI were observed in cranial ner ve nuclei (trigeminal, facial, vestibular, cochlear, vagus, and hypogl ossal nerves) and in relay nuclei (pontine, olivary, lateral reticular , cuneate, gracile nucleus, and locus coeruleus). In the cerebellum, N AIP-LI was found within both Purkinje and nuclear cells (interposed an d lateral nuclei). Finally, within the spinal cord, NAIP-LI was detect ed in Clarke's column and in motor neurons. Taken together, these resu lts indicate that NAIP-LI is distributed broadly in the CNS. However, high levels of NAIP-LI were restricted to those neuronal populations t hat have been reported to degenerate in SMA. This anatomical correspon dence provides additional evidence for NAIP involvement in the neurode generation observed in acute SMA. (C) 1997 Wiley-Liss, Inc.