Distribution of neuronal apoptosis inhibitory protein-like immunoreactivity in the rat central nervous system

Abstract

We have recently shown that spinal muscular atrophy (SMA), an autosomal recessive disorder characterized by motor neuron loss, is associated with deletion of a gene that encodes the neuronal apoptosis inhibitory protein (NAIP). In the present study, we have examined the distribution of NAIP-like immunoreactivity (NAIP-LI) in the rat central nervous system (CNS) by using an affinity-purified polyclonal antibody against NAIP. In the forebrain, immunoreactive neurons were detected in the cortex, the hippocampus (pyramidal cells, dentate granule cells, and interneurons), the striatum (cholinergic interneurons), the basal forebrain (ventral pallidum, medial septal nucleus, and diagonal band), the thalamus (lateral and ventral nuclei), the habenula, the globus pallidus, and the entopenduncular nucleus. In the midbrain, NAIP-LI was located 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 nerve nuclei (trigeminal, facial, vestibular, cochlear, vagus, and hypoglossal nerves) and in relay nuclei (pontine, olivary, lateral reticular, cuneate, gracile nucleus, and locus coeruleus). In the cerebellum, NAIP-LI was found within both Purkinje and nuclear cells (interposed and lateral nuclei). Finally, within the spinal cord, NAIP-LI was detected in Clarke's column and in motor neurons. Taken together, these results indicate that NAIP-LI is distributed broadly in the CNS. However, high levels of NAIP-LI were restricted to those neuronal populations that have been reported to degenerate in SMA. This anatomical correspondence provides additional evidence for NAIP involvement in the neurodegeneration observed in acute SMA.

The inhibitors of apoptosis (IAPs) and their emerging role in cancer

“…This autosomal recessive condition is caused by Roy et al, 1995;Chen et al, 1998;mNAIP1-6, mouse NAIP-1 through 6 (AF007769) Yaraghi et al, 1998; NAIP-rs 1 through 6, NAIP related sequence 1 (U66324), 2 (U66325), 3 (U66326), 4 (U66327), 5 (U66328), 6 (U66329) Scharf et al, 1996; rNAIP, Rat NAIP (partial cDNA) Korneluk et al, (unpublished); HIAP1, human IAP1 (U45878) Liston et al, 1996; cIAP2, cellular IAP2 (L49432) Rothe et al, 1995; MIHC, mammalian IAP homolog C (U37546) Uren et al, 1996; hITA, human inhibitor of T-cell apoptosis, Nicholl et al, 1996; MIAP1, mouse IAP1 (U88908) Liston et al, 1997;RIAP1, rat IAP1 Holcik et al, (unpublished); PIAP, porcine IAP (U79142) Stehlik et al, 1998b; ITA, inhibitor of T-cell apoptosis (U27466) Digby et al, 1996;ch-IAP1, chicken a severe loss of motor neurons which results in fatal accid paralysis (Dubowitz, 1995). While the contiguous SMN gene has been found to be causative of SMA , the tissue expression of NAIP (Xu et al, 1997a) combined with its strong in vitro (Liston et al, 1996) and in vivo (Xu et al, 1997b) neuroprotective eect make it a likely candidate for modi®cation of the SMA phenotype. It is postulated that motor neurons missing NAIP withstand the low cellular levels of SMN protein poorly and dying earlier than they would have otherwise resulting in more severe disease (MacKenzie, 1998).…”

Distribution of Neuronal Apoptosis Inhibitory Protein in Human Tissues

“…The first discovered mammalian IAP, neuronal apoptosis inhibitory protein (NAIP), or baculoviral IAP repeat-containing protein 1 (BIRC1), was cloned as a candidate gene for the childhood disorder spinal muscular atrophy (SMA) (Roy et al 1995). The expression of NAIP has thus been studied extensively in the central nervous system (CNS) (Xu et al 1997b;Pari et al 2000) and during development (IngramCrooks et al 2002). The distribution of NAIP-like immunoreactivity was examined in the rat CNS by using an affinity-purified polyclonal antibody (E1.0) against human NAIP (Xu et al 1997b).…”

“…The expression of NAIP has thus been studied extensively in the central nervous system (CNS) (Xu et al 1997b;Pari et al 2000) and during development (IngramCrooks et al 2002). The distribution of NAIP-like immunoreactivity was examined in the rat CNS by using an affinity-purified polyclonal antibody (E1.0) against human NAIP (Xu et al 1997b). This investigation demonstrated a wide distribution of NAIP-like species in the rat CNS.…”

“…This investigation demonstrated a wide distribution of NAIP-like species in the rat CNS. Although low-to-moderate levels of NAIP-like immunoreactivity were observed in the cortex and hippocampus, intense staining was detected within a wide variety of subcortical brain regions (Xu et al 1997b). These included the thalamus, cranial nerve nuclei, brainstem relay nuclei, cerebellum, and Clarke's column of the spinal cord.…”

The hippocampal neurons of neuronal apoptosis inhibitory protein 1 (NAIP1)-deleted mice display increased vulnerability to kainic acid-induced injury

“…We have shown that the neuronal apoptosis inhibitory protein (NAIP) is deleted in a significant proportion of SMA patients (2). Full-length functional NAIP is absent in most individuals with type I SMA, and there exists a close correlation between the regional distribution of NAIP in the CNS and the neurodegenerative alterations in SMA (3). These observations are consistent with the neurodegenerative character of SMA.…”