NT-3 facilitates hippocampal plasticity and learning and memory by regulating neurogenesis

Section on Neural Development and Plasticity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Learning &amp Memory (Impact Factor: 3.66). 05/2006; 13(3):307-15. DOI: 10.1101/lm.76006
Source: PubMed


In the adult brain, the expression of NT-3 is largely confined to the hippocampal dentate gyrus (DG), an area exhibiting significant neurogenesis. Using a conditional mutant line in which the NT-3 gene is deleted in the brain, we investigated the role of NT-3 in adult neurogenesis, hippocampal plasticity, and memory. Bromodeoxyuridine (BrdU)-labeling experiments demonstrated that differentiation, rather than proliferation, of the neuronal precursor cells (NPCs) was significantly impaired in DG lacking NT-3. Triple labeling for BrdU, the neuronal marker NeuN, and the glial marker GFAP indicated that NT-3 affects the number of newly differentiated neurons, but not glia, in DG. Field recordings revealed a selective impairment in long-term potentiation (LTP) in the lateral, but not medial perforant path-granule neuron synapses. In parallel, the NT-3 mutant mice exhibited deficits in spatial memory tasks. In addition to identifying a novel role for NT-3 in adult NPC differentiation in vivo, our study provides a potential link between neurogenesis, dentate LTP, and spatial memory.

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    • "BDNF plays various roles in regulating neuronal structure, function, and long-term survival in the developing and adult brain and also in plasticity-related changes in long-term drug exposure or abuse (Akbarian et al., 2001; Bolanõs and Nestler, 2004; Hatami et al., 2007). There is also substantial evidence documenting the role of BDNF in synaptic plasticity in the hippocampus , neurogenesis, and improvement of learning and memory (Johnston et al., 1999; Johnston and Rose, 2001; Alonso et al., 2002; Shimazu et al., 2006). Direct hippocampal infusion of BDNF produces anxiolytic and antidepressant effects (Siuciak et al., 1997; Shimizu et al., 2003; Cirulli et al., 2004). "
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    ABSTRACT: Prenatal morphine exposure throughout pregnancy can induce a series of neurobehavioral and neurochemical disturbances by affecting central nervous system development. This study was designed to investigate the effects of an enriched environment on behavioral deficits and changes in hippocampal brain-derived neurotrophic factor (BDNF) levels induced by prenatal morphine in rats. On pregnancy days 11–18, female Wistar rats were randomly injected twice daily with saline or morphine. Offspring were weaned on postnatal day (PND) 21. They were subjected to a standard rearing environment or an enriched environment on PNDs 22–50. On PNDs 51–57, the behavioral responses including anxiety and depression-like behaviors, and passive avoidance memory as well as hippocampal BDNF levels were investigated. The light/dark (L/D) box and elevated plus maze (EPM) were used for the study of anxiety, forced swimming test (FST) was used to assess depression-like behavior and passive avoidance task was used to evaluate learning and memory. Prenatal morphine exposure caused a reduction in time spent in the EPM open arms and a reduction in time spent in the lit side of the L/D box. It also decreased step-through latency and increased time spent in the dark side of passive avoidance task. Prenatal morphine exposure also reduced immobility time and increased swimming time in FST. Postnatal rearing in an enriched environment counteracted with behavioral deficits in the EPM and passive avoidance task, but not in the L/D box. This suggests that exposure to an enriched environment during adolescence period alters anxiety profile in a task-specific manner. Prenatal morphine exposure reduced hippocampal BDNF levels, but enriched environment significantly increased BDNF levels in both saline- and morphineexposed groups. Our results demonstrate that exposure to an enriched environment alleviates behavioral deficits induced by prenatal morphine exposure and up-regulates the decreased levels of BDNF. BDNF may contribute to the beneficial effects of an enriched environment on prenatal morphine-exposed to rats.
    Neuroscience 10/2015; 305(1):372-383. DOI:10.1016/j.neuroscience · 3.36 Impact Factor
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    • "New granule cell neurons arise from the neural progenitors of the subgranular zone of the dentate gyrus (Song et al., 2002) and many factors including both intracellular and extracellular contribute towards the different stages of neurogenesis. Trophic factors such as FGF-2 (Zhao et al., 2007) and NT-3 (Shimazu et al., 2006) along with growth factors such as IGF-1 (Aberg et al., 2000) and VEGF (Jin et al., 2002) have been shown to have an effect on different phases of neurogenesis in the dentate gyrus. We have previously shown that neuropeptide TLQP-62 increases adult neurogenesis (Thakker-Varia et al., 2007) and in this study using markers of different stages of proliferation we have deciphered the exact stage of neuronal development at which TLQP-62 has the most effect. "
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    Stem Cell Research 03/2014; 12(3):762-777. DOI:10.1016/j.scr.2014.03.005 · 3.69 Impact Factor
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    • "In LR rats, the FST induced the transcriptional activation of genes that positively regulate neurogenesis in the adult hippocampus. Notably, Ntf3 (neurotrophin 3; +2.469) facilitates hippocampal plasticity by promoting neurogenesis in the dentate gyrus [26], Nog (noggin; +2.177) is a BMP antagonist that diverts stem cells from a glial to a neuronal fate [27], and Sox2 (SRY (sex-determining region Y)-box 2; +2.201) maintains neural stem cell properties, including proliferation/survival, self-renewal, and neurogenesis [28]. Moreover, FST exposure led to overexpression of Tgfb1 (transforming growth factor, beta 1; +2.219) and Smad7 (SMAD family member 7; +2.443) mRNA in the hippocampus of LR rats. "
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    Human genomics 02/2014; 8(1):4. DOI:10.1186/1479-7364-8-4 · 2.15 Impact Factor
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