Dendritic Morphology of Developing Hippocampal Neurons in <i>Cyp11a1</i> Null Mice

Abstract

<b><i>Introduction:</i></b> Neurosteroids have a variety of neurological functions, such as neurite growth, neuroprotection, myelination, and neurogenesis. P450scc, encoded by <i>CYP11A1</i> gene, is the cholesterol side chain cleavage enzyme that catalyzes the first and rate-limiting step in steroidogenesis. In this study, we examine the dendritic morphology in developing hippocampal neurons of <i>Cyp11a1</i> null mice at P15, a critical period for synapse formation and maturation. <b><i>Methods:</i></b> Knockout mice were maintained until P15 with hormone administration. The Golgi-Cox method stained CA1 and CA3 pyramidal neurons in the hippocampus to reveal dendritic morphology. <b><i>Results:</i></b> We demonstrated that <i>Cyp11a1</i> null mice usually die within 7 days after birth and thus collected brain samples at postnatal day 5 (P5) for examination. There was significant shrinkage of dendrite size and diminishment of dendritic branching in CA1 and CA3 pyramidal neurons in the hippocampus of <i>Cyp11a1</i> null mice, suggesting a developmental delay. We wonder if this delay may catch up later in life. Since the age of P15 is a critical period for synapse formation and maturation, the <i>Cyp11a1</i> null mice were rescued by receiving hormone administration until P15 that the dendritic morphology in the developing hippocampal neurons could be examined. The results indicated that the total dendritic length, the number of dendritic branches, as well as dendritic arborization in the CA1 and CA3 pyramidal neurons are significantly decreased in P15 knockout mice when compared to the wild type. The spine densities were also significantly decreased. In addition, the Western blot analysis revealed decreased PSD-95 expression levels in the knockout mice compared to the wild type at P15. <b><i>Conclusion:</i></b> These results suggested that <i>Cyp11a1</i> deficiency impairs the dendritic structures in the developing hippocampal pyramidal neurons.