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Front. Cell. Neurosci. | doi: 10.3389/fncel.2018.00340

Regulation of hippocampal synaptic function by the metabolic hormone, leptin: Implications for health and neurodegenerative disease

 Jenni Harvey1* and Gemma McGregor1
  • 1University of Dundee, United Kingdom

The role of the endocrine hormone leptin in regulating food intake and body weight in the hypothalamus are well documented. However the CNS targets for leptin are not restricted to the hypothalamus as high levels of leptin receptor expression are evident in several brain regions involved in higher cognitive functions including the hippocampus. Numerous studies have identified a cognitive enhancing role for leptin in the hippocampus as exogenous application of this hormone facilitates hippocampal-dependent learning and memory, whereas lack or insensitivity to leptin results in significant memory deficits. Leptin also markedly influences the key cellular events that are implicated in learning and memory including activity-dependent hippocampal synaptic plasticity and glutamate receptor trafficking. Like other metabolic hormones, there is a significant decline in neuronal sensitivity to leptin with age as the ability of leptin to regulate hippocampal synaptic function is substantially reduced in aged compared to adult. Clinical studies have also identified a link between leptin and neurodegenerative disorders such as Alzheimer’s disease (AD). Thus the leptin system may be a novel target for developing therapies to treat AD. In support of this, accumulating evidence indicates that leptin has cognitive enhancing and neuroprotective actions in various models of AD. Here we review the evidence that leptin is a potent regulator of hippocampal synaptic function, and discuss how age-related alterations in this hormonal system influences neurodegenerative disease.

Keywords: Leptin, Hippocampus, synaptic plasticity, Alzheimer's disease, Amyloid

Received: 12 Jul 2018; Accepted: 13 Sep 2018.

Edited by:

Marco Mainardi, Scuola Normale Superiore di Pisa, Italy

Reviewed by:

Laura M. Frago, Universidad Autónoma de Madrid, Spain
Jong-Woo Sohn, Korea Advanced Institute of Science & Technology (KAIST), South Korea
Salvatore Fusco, Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore, Italy  

Copyright: © 2018 Harvey and McGregor. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Jenni Harvey, University of Dundee, Dundee, United Kingdom,