Spatiotemporal expression of MANF in the developing rat brain.

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PloS one, ISSN: 1932-6203, Vol: 9, Issue: 2, Page: e90433

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10.1371/journal.pone.0090433; 10.1371/journal.pone.0090433.g009; 10.1371/journal.pone.0090433.g007; 10.1371/journal.pone.0090433.g001; 10.1371/journal.pone.0090433.g006; 10.1371/journal.pone.0090433.g005; 10.1371/journal.pone.0090433.g002; 10.1371/journal.pone.0090433.g008; 10.1371/journal.pone.0090433.g003; 10.1371/journal.pone.0090433.g004
PMC3938758; 3938758
Haiping Wang; Zunji Ke; Alexander Alimov; Mei Xu; Jacqueline A. Frank; Shengyun Fang; Jia Luo; Xianglin Shi
Public Library of Science (PLoS); Figshare
Biochemistry, Genetics and Molecular Biology; Agricultural and Biological Sciences; Biological Sciences; Anatomy and physiology; Computational biology; Molecular genetics; gene expression; developmental biology; histology; Model organisms; Animal models; rat; Molecular cell biology; Signal transduction; Signaling in selected disciplines; Developmental signaling; neuroscience; Developmental neuroscience; manf; cerebral; cortex; immunohistochemistry; immunoblotting; olfactory; Medical Nutrition; Medical Pharmacology; Pharmacology, Toxicology and Environmental Health
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Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an evolutionarily conserved neurotrophic factor which exhibited neuroprotective properties. Recent studies suggested that MANF may play a role in the neural development of Drosophila and zebra fishes. In this study, we investigated the spatiotemporal expression of MANF in the brain of postnatal and adult rats. MANF expression appeared wide spread and mainly localized in neurons. In the cerebral cortex, neurons in layer IV and VI displayed particularly strong MANF immunoreactivity. In the hippocampus, intensive MANF expression was observed throughout the subfields of Cornu Amonis (CA1, CA2, and CA3) and the granular layer of the dentate gyrus (DG). In the substantia nigra, high MANF expression was shown in the substantia nigra pars compacta (SNpc). In the thalamus, the anterodorsal thalamic nucleus (ADTN) exhibited the highest MANF immunoreactivity. In the hypothalamus, intensive MANF immunoreactivity was shown in the supraoptic nucleus (SON) and tuberomammillary nucleus (TMN). In the cerebellum, MANF was localized in the external germinal layer (EGL), Purkinje cell layer (PCL), internal granule layer (IGL) and the deep cerebellar nuclei (DCN). We examined the developmental expression of MANF on postnatal day (PD) 3, 5, 7, 9, 15, 21, 30 and adulthood. In general, the levels of MANF were high in the early PDs (PD3 and PD5), and declined gradually as the brain matured; MANF expression in the adult brain was the lowest among all time points examined. However, in some structures, such as PCL, IGL, SON, TMN and locus coeruleus (LC), high expression of MANF sustained throughout the postnatal period and persisted into adulthood. Our results indicated that MANF was developmentally regulated and may play a role in the maturation of the central nervous system (CNS).