Leptin promotes rapid dynamic changes in hippocampal dendritic morphology.
Recent studies have implicated the hormone leptin in synaptic plasticity associated with neuronal development and learning and memory. Indeed, leptin facilitates hippocampal long-term potentiation and leptin-insensitive rodents display impaired hippocampal synaptic plasticity suggesting a role for endogenous leptin. Structural changes are also thought to underlie activity-dependent synaptic plasticity and this may be regulated by specific growth factors. As leptin is reported to have neurotrophic actions, we have examined the effects of leptin on the morphology and filopodial outgrowth in hippocampal neurons. Here, we demonstrate that leptin rapidly enhances the motility and density of dendritic filopodia and subsequently increases the density of hippocampal synapses. This process is dependent on the synaptic activation of NR2A-containing NMDA receptors and is mediated by the MAPK (ERK) signaling pathway. As dendritic morphogenesis is associated with activity-dependent changes in synaptic strength, the rapid structural remodeling of dendrites by leptin has important implications for its role in regulating hippocampal synaptic plasticity and neuronal development.
O'Malley
Dervla
D
Neurosciences Institute, Division of Pathology and Neuroscience, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK.
MacDonald
Neil
N
Mizielinska
Sarah
S
Connolly
Christopher N
CN
Irving
Andrew J
AJ
Harvey
Jenni
J
D000199:Actins / Q000378:metabolism; D000730:Androstadienes / Q000378:metabolism; D000818:Animals; D048430:Cell Shape; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure*; D006624:Hippocampus / Q000166:cytology*; D020738:Leptin / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009024:Morphogenesis; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism; D054411:Receptors, Leptin; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure; D016704:Synapsins / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D000077191:Wortmannin
D000199:Actins; D000730:Androstadienes; D020738:Leptin; D047428:Protein Kinase Inhibitors; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D016194:Receptors, N-Methyl-D-Aspartate; D016704:Synapsins; D020928:Mitogen-Activated Protein Kinases; D000077191:Wortmannin