Inhibitor‐of‐apoptosis proteins (IAPs), including neuronal apoptosis inhibitory protein (NAIP), inhibit cell death. Other IAPs inhibit key caspase proteases which effect cell death, but the mechanism by which NAIP acts is unknown. Here we report that NAIP, through its third baculovirus inhibitory repeat domain (BIR3), binds the neuron‐restricted calcium‐binding protein, hippocalcin, in an interaction promoted by calcium. In neuronal cell lines NSC‐34 and Neuro‐2a, over‐expression of the BIR domains of NAIP (NAIP‐BIR1–3) counteracted the calcium‐induced cell death induced by ionomycin and thapsigargin. This protective capacity was significantly enhanced when NAIP‐BIR1–3 was co‐expressed with hippocalcin. Over‐expression of the BIR3 domain or hippocalcin alone did not substantially enhance cell survival, but co‐expression greatly increased their protective effects. These data suggest synergy between NAIP and hippocalcin in facilitating neuronal survival against calcium‐induced death stimuli mediated through the BIR3 domain. Analysis of caspase activity after thapsigargin treatment revealed that caspase‐3 is activated in NSC‐34, but not Neuro‐2a, cells. Thus NAIP, in conjunction with hippocalcin, can protect neurons against calcium‐induced cell death in caspase‐3‐activated and non‐activated pathways.

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BRCA-1 is a tumor suppressor gene that plays a role in DNA repair and cellular growth control. Here we show that BRCA-1 mRNA is expressed by embryonic rat brain and is localized to the neuroepithelium containing neuronal precursor cells. The expression of BRCA-1 decreases during rat brain development, but BRCA-1 is expressed postnatally by proliferating neuronal precursor cells in the developing cerebellum. Neural stem cells (NSC) prepared from embryonic rat brain and cultured in the presence of epidermal growth factor were positive for BRCA-1. Induction of NSC differentiation resulted in down-regulation of BRCA-1 expression as shown by RNA and protein analyses. In addition to embryonic cells, BRCA-1 is also present in NSC prepared from adult rat brain. In adult rats, BRCA1 was expressed by cells in the walls of brain ventricles and in choroid plexus. The results show that BRCA-1 is present in embryonic and adult rat NSC and that the expression is linked to NSC proliferation.

The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is present in many regions of the adult and developing brain as are receptors for PACAP. PACAP stimulates different signalling cascades in neurons, involving cAMP, MAP kinase, and calcium. These characteristics suggest that PACAP may influence neuronal development. Here we have studied the effects of PACAP on mesencephalic dopaminergic neurons using primary cultures from embryonic rats. PACAP increased the number of tyrosine hydroxylase (TH)-immunoreactive neurons, elevated TH protein, and enhanced tritiated dopamine uptake in these cultures. Moreover, PACAP counteracted the effects of 6-hydroxydopamine treatments, which induce cell death of dopaminergic neurons. In situ hybridisation showed that both PACAP and PACAP receptor type 1 are present in developing and adult rat mesencephalon. These results show that PACAP has a neurotrophic action on dopaminergic neurons and partially protects them against 6-OHDA induced neurotoxicity.