Leptin Increases Adult Hippocampal Neurogenesis in Vivo and in Vitro

Department of Pharmacology, University of Texas Health Science Center, San Antonio, TX 78229, USA.
Journal of Biological Chemistry (Impact Factor: 4.57). 07/2008; 283(26):18238-47. DOI: 10.1074/jbc.M800053200
Source: PubMed


Leptin, an adipose-derived hormone, has been implicated in several physiological processes involving the hippocampus. However,
the role of leptin in adult hippocampal neurogenesis remains unknown. Here we show that leptin regulates neurogenesis in the
dentate gyrus of adult mice as well as in cultured adult hippocampal progenitor cells. Chronic administration of leptin to
adult mice increased cell proliferation without significant effects on the differentiation and the survival of newly proliferated
cells in the dentate gyrus. The expression of the long form leptin receptor, LepRb, was detected in hippocampal progenitor
cells by reverse transcription-PCR and immunohistochemistry. Leptin treatment also increased proliferation of cultured adult
hippocampal progenitor cells. Analysis of signal transduction pathways revealed that leptin stimulated phosphorylation of
Akt and STAT3 but not ERK1/2. Furthermore, pre-treating the cells with specific inhibitors of Akt or STAT3 attenuated leptin-induced
cell proliferation in a dose-dependent manner. Taken together, our results support a role for leptin in adult hippocampal
neurogenesis and suggest the involvement of the Akt and STAT3 signaling pathways in mediating the actions of leptin on neurogenesis.

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    • "mice increases neurogenesis in the dentate gyrus (Garza et al. 2008). Epidemiological studies also show an inverse relationship between leptin levels and risk of developing dementia of the Alzheimer type (Lieb et al. 2009). "
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    ABSTRACT: Leptin, identified as an antiobesity hormone, also has important role in responses to stress and processing of memory. This study was designed to determine effects of academic examination stress-induced changes in serum leptin and its impact on academic performance. Eighty five healthy female students (age 19-21 years; BMI 21.9 ± 1.6) were recruited for the study. Serum leptin and cortisol were monitored at base line (beginning of academic session) and on the day of examination; using a standardized ELISA kit. Acute perception of academic examination stress was determined with the help of a questionnaire derived from Hamilton Anxiety Scale and self report of stress perception. Academic performance was evaluated by the percentage of marks obtained in the examination. Serum cortisol levels were positively correlated (p < 0.01) with the subjective perception of examination stress but not with academic performance. There was an inverted U-shape relationship between level of stress and academic performance. Leptin increased in all stress groups and correlated (p < 0.01) positively with academic performance. There was an inverted U-shape relationship between level of stress and circulating leptin. The findings suggest the peptide hormone, leptin, is a biomarker of stress perception and a mediator of facilitating effects of stress on cognition.
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    • "survival and neurogenesis (Garza et al., 2008; Moon et al., 2009; Spasic et al., 2009; Decressac et al., 2010). In recent experiments we showed that NPY infusion in the basolateral amygdala normalized the anxiety of the animals subjected to inescapable footshock (IFS) (Hendriksen et al., 2012). "
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    ABSTRACT: We used the inescapable foot shock paradigm (IFS) in rats as an animal model for post-traumatic stress disorder (PTSD). Previously we showed that exercise reversed the enhanced stress sensitivity induced by IFS. From literature it is known that food restriction has antidepressant and anxiolytic effects. Since both treatments influence energy expenditure, we questioned whether food restriction reduces anxiety in the IFS model via a comparable, NPY dependent mechanism as enrichment. Anxiety of IFS-exposed animals was measured as change in locomotion and freezing after sudden silence in an open field test, before and after two weeks of food restriction. In addition a forced swim test (FST) was performed. Next, using qPCR, the expression of neuropeptide Y (NPY) and the neuropeptide Y1 receptor (Y1 receptor) was measured in the amygdala. Food restriction increased locomotion and decreased freezing behavior both in control and IFS animals. These effects were small. IFS-induced anxiety was not abolished after two weeks of food restriction. IFS did not influence immobility or the duration of swimming in the FST of animals fed ad libitum. However, food restriction increased swimming and decreased the duration of immobility in IFS-exposed animals. Y1 receptor expression in the basolateral amygdala decreased after both IFS and food restriction. Although food restriction seems to induce a general anxiolytic effect, it does not operate via enhanced Y1 receptor expression and has no effect on the more pathogenic anxiety induced by IFS. Copyright © 2014. Published by Elsevier B.V.
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    • "Irf3 and Irf7 have been shown to induce type 1 interferons, which subsequently stimulate Jak-Stat signal transduction pathways leading to upregulated transcription of various interferon-stimulated genes [54–56]. Leptin and its receptor, Lepr, have been shown to be involved in leptin-dependent adult hippocampal neurogenesis [57] and mediated neuroprotection of dopaminergic cells via activation of Jak-Stat, mitogen-activated protein kinases (MEK)/extracellular signal-regulated kinases (ERK) and growth factor receptor-bound protein 2 (GRB2) signaling pathways in a mouse model of Parkinson’s disease [58]. The role of the Jak-Stat signaling pathway in the brain, however, is unclear. "
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