Leptin prevents hippocampal synaptic disruption and neuronal cell death induced by amyloid β.

Doherty, Gayle H., Beccano-Kelly, Dayne ORCID: https://orcid.org/0000-0003-3592-8354, Yan, Shi Du, Gunn-Moore, Frank J. and Harvey, Jenni 2012. Leptin prevents hippocampal synaptic disruption and neuronal cell death induced by amyloid β. Neurobiology of Aging 34 (1) , pp. 226-237. 10.1016/j.neurobiolaging.2012.08.003

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Abstract

Accumulation of amyloid-β (Aβ) is a key event mediating the cognitive deficits in Alzheimer's disease (AD) as Aβ promotes synaptic dysfunction and triggers neuronal death. Recent evidence has linked the hormone leptin to AD as leptin levels are markedly attenuated in AD patients. Leptin is also a potential cognitive enhancer as it facilitates the cellular events underlying hippocampal learning and memory. Here we show that leptin prevents the detrimental effects of Aβ1–42 on hippocampal long-term potentiation. Moreover leptin inhibits Aβ1–42-driven facilitation of long-term depression and internalization of the 2-amino-3-(5-methyl-3-oxo-1,2- oxazol-4-yl)propanoic acid (AMPA) receptor subunit, GluR1, via activation of PI3-kinase. Leptin also protects cortical neurons from Aβ1–42-induced cell death by a signal transducer and activator of transcription-3 (STAT-3)-dependent mechanism. Furthermore, leptin inhibits Aβ1–42-mediated upregulation of endophilin I and phosphorylated tau in vitro, whereas cortical levels of endophilin I and phosphorylated tau are enhanced in leptin-insensitive Zucker fa/fa rats. Thus leptin benefits the functional characteristics and viability of neurons that degenerate in AD. These novel findings establish that the leptin system is an important therapeutic target in neurodegenerative conditions.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Publisher:	Elsevier
ISSN:	0197-4580
Date of Acceptance:	2 August 2012
Last Modified:	10 Nov 2022 11:20
URI:	https://orca.cardiff.ac.uk/id/eprint/150129

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