Age-dependent Regulation of Excitatory Synaptic Transmission at Hippocampal Temporoammonic-CA1 Synapses by Leptin

Overview

Journal Neurobiol Aging

Publisher Elsevier

Specialties Geriatrics
Neurology
Physiology

Date 2018 Jun 4

PMID 29860205

Citations 13

Authors

Gemma McGregor

Leigh Clements

Adham Farah

Andrew J Irving

Jenni Harvey

Affiliations

Soon will be listed here.

Abstract

The hippocampus is a key target for the hormone leptin and leptin regulation of excitatory synaptic transmission at Schaffer-collateral-CA1 synapses during aging are well documented. However, little is known about the age-dependent actions of leptin at the temporoammonic (TA) input to CA1 neurons. Here we show that leptin induces a novel form of N-methyl-D-aspartate receptor-dependent long-term depression (LTD) at adult (12-24 weeks old) TA-CA1 synapses. Leptin-induced LTD requires activation of canonical Janus tyrosine kinase 2- signal transducer and activator of transcription signaling and removal of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors from synapses. Moreover, leptin-induced LTD is occluded by activity-dependent LTD at TA-CA1 synapses. By contrast, leptin has no effect on excitatory synaptic transmission at aged (12-14 months old) TA-CA1 synapses, and low-frequency stimulation also fails to induce LTD at this age. These findings demonstrate clear age-related alterations in the leptin sensitivity of TA-CA1 synapses and provide valuable information on how the leptin system alters with age. As leptin has been linked to Alzheimer's disease, these findings have important implications for understanding of age-related disorders such as Alzheimer's disease.

Citing Articles

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Neuroprotective Effects of Leptin on the APP/PS1 Alzheimer's Disease Mouse Model: Role of Microglial and Neuroinflammation.

Ma J, Hou Y, Liao Z, Ma Z, Zhang X, Wang J Degener Neurol Neuromuscul Dis. 2023; 13:69-79.

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G-protein coupled estrogen receptor (GPER1) activation promotes synaptic insertion of AMPA receptors and induction of chemical LTP at hippocampal temporoammonic-CA1 synapses.

Clements L, Alexander A, Hamilton K, Irving A, Harvey J Mol Brain. 2023; 16(1):16.

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Food for Thought: Leptin and Hippocampal Synaptic Function.

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PMID: 35784728 PMC: 9247348. DOI: 10.3389/fphar.2022.882158.

A Review of miRNAs as Biomarkers and Effect of Dietary Modulation in Obesity Associated Cognitive Decline and Neurodegenerative Disorders.

Perdoncin M, Konrad A, Wyner J, Lohana S, Pillai S, Pereira D Front Mol Neurosci. 2021; 14:756499.

PMID: 34690698 PMC: 8529023. DOI: 10.3389/fnmol.2021.756499.

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