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Recent studies indicate that bone morphogenetic protein-4 (BMP4) and Noggin not only play an important role in the early development of the nervous system, but may also play a role in postnatal central nervous system (CNS) development. In this study, we examined the relative levels and localization of Noggin and BMP4 mRNA in the hippocampus of rats of different developmental stages with reverse transcriptase–polymerase chain reaction (RT–PCR) and in situ hybridization (ISH). RT–PCR showed that the temporal changes in the levels of expression of Noggin and BMP4 were different. The peak level of expression of Noggin mRNA was observed at embryonic day 13 (E13), subsequently gradually declined at 1–3 months (P1–3M) postnatal, and was detected only at a low level at P18M. In contrast, the expression of BMP4 mRNA increased gradually during embryonic development, reached a maximal level at 3 weeks (W) postnatal, and declined only slightly through P18M. In situ hybridization revealed that at embryonic stages, Noggin mRNA was localized throughout all hippocampal regions, whereas at early postnatal ages, Noggin mRNA was primarily localized in the anterior subiculum. At embryonic and early postnatal stages, no significant BMP4 mRNA expression was detectable in the hippocampus. At later postnatal ages, however, Noggin and BMP4 mRNA expression was observed in similar patterns. At 1–3 months postnatal, expression of BMP4 was observed mainly in the dentate gyrus and in the CA1–CA3 pyramidal cell layers. Lower hybridization signals were observed in the hilus and subiculum. Taken together, our results demonstrate that Noggin and BMP4 are expressed in embryonic and postnatal hippocampus, and that the temporal and spatial patterns of their expression are developmentally regulated. These data suggest that Noggin and BMP4 play important roles in hippocampal development. [Copyright &y& Elsevier]

Abstract: Recent human studies suggest that abnormal development of oligodendrocytes (OLs) is an important component in the pathophysiology of schizophrenia. However, less information is available regarding effects of antipsychotics on OLs'' development. In the present study, young adult C57BL/6 mice were given haloperidol (HAL; 2mg/kg/day) in their drinking water for three or six weeks. At the conclusion of the drug treatment, mice were sacrificed and the numbers of NG2- and Olig2-expressing cells in the brain regions of the corpus callosum, hippocampus and cerebral cortex were quantified. NG2 is a specific marker for oligodendroglia precursor cells (OPCs); Olig2 marks glial progenitors. HAL treatment for three weeks increased the number of NG2-expressing cells in the corpus callosum; HAL treatment for three and six weeks increased the numbers of Olig2-expressing cells in all three brain regions and increased the levels of Olig2 expression in the same brain regions. These results suggest that HAL treatment activates adult OPCs, which divide infrequently under normal conditions but respond to a variety of insulting factors by proliferation and differentiation. However, our further observations showed no changes in the number of mature OLs and the amount of myelin basic protein in HAL-treated mice, suggesting the drug treatment has no effect on the maturation of OLs. In addition, HAL treatment did not increase the numbers of GFAP- and CD68-expressing cells, suggesting that no gliosis and inflammatory responses occurred while the drug activated the quiescent OPCs in adult brain. These results suggest that HAL treatment may target the development of OLs. [Copyright &y& Elsevier]

Recent studies indicate that Noggin not only plays an important role in the early development of the nervous system, but may also plays a role in postnatal central nervous system (CNS) development. In this study, we examined the relative levels and localization of Noggin mRNA in the hippocampus of rats of different developmental stages with reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization. RT-PCR showed that the peak level of expression of Noggin mRNA was observed at embryonic day 13 (E13), subsequently gradually declined at 1–3 months (P1-3M) postnatal, and was detected only at a low level at P18M. In situ hybridization revealed that at embryonic stages, Noggin mRNA was localized throughout all hippocampal regions, whereas at early postnatal ages, Noggin mRNA was primarily localized in the anterior subiculum. At later postnatal ages, Noggin mRNA expression was obviously observed in the dentate gyrus and in the CA1-CA3 pyramidal cell layers. Taken together, our results demonstrate that Noggin is expressed in embryonic and postnatal hippocampus, and that the temporal and spatial patterns of its expression is developmentally regulated. [Copyright &y& Elsevier]