Adenosine Augmentation Evoked by an ENT1 Inhibitor Improves Memory Impairment and Neuronal Plasticity in the APP/PS1 Mouse Model of Alzheimer’s Disease

Autor: Hsing-Lin Lai, Jim-Min Fang, Ching-Pang Chang, Hui-Mei Chen, Sin-Jhong Cheng, David Blum, Yu-Han Kao, Luc Buée, Yijuang Chern, Emilie Faivre, Chun-Jung Lin, Yu-Ping Liao, Chia-Chia Lee
Přispěvatelé: STMicroelectronics [Rousset] (ST-ROUSSET), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Blum, David, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Adenosine
Receptor
Adenosine A2A
Neuroscience (miscellaneous)
Hippocampus
Mice
Transgenic
Plaque
Amyloid
Neurotransmission
Equilibrative nucleoside transporter 1
Synaptic Transmission
Equilibrative Nucleoside Transporter 1
Amyloid beta-Protein Precursor
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Alzheimer Disease
Presenilin-1
medicine
Animals
Cognitive Dysfunction
[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
ComputingMilieux_MISCELLANEOUS
Cerebral Cortex
Memory Disorders
Glycogen Synthase Kinase 3 beta
Neuronal Plasticity
biology
Glutamate receptor
Long-term potentiation
medicine.disease
Cyclic AMP-Dependent Protein Kinases
Disease Models
Animal
030104 developmental biology
medicine.anatomical_structure
nervous system
Neurology
Schaffer collateral
Astrocytes
biology.protein
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Alzheimer's disease
Neuroscience
030217 neurology & neurosurgery
medicine.drug
Zdroj: Molecular Neurobiology
Molecular Neurobiology, Humana Press, 2018, ⟨10.1007/s12035-018-1030-z⟩
Molecular Neurobiology, 2018, ⟨10.1007/s12035-018-1030-z⟩
ISSN: 0893-7648
DOI: 10.1007/s12035-018-1030-z⟩
Popis: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairment and synaptic dysfunction. Adenosine is an important homeostatic modulator that controls the bioenergetic network in the brain through regulating receptor-evoked signaling pathways, bioenergetic machineries, and epigenetic-mediated gene regulation. Equilibrative nucleoside transporter 1 (ENT1) is a major adenosine transporter that recycles adenosine from the extracellular space. In the present study, we report that a small adenosine analogue (designated J4) that inhibited ENT1 prevented the decline in spatial memory in an AD mouse model (APP/PS1). Electrophysiological and biochemical analyses further demonstrated that chronic treatment with J4 normalized the impaired basal synaptic transmission and long-term potentiation (LTP) at Schaffer collateral synapses as well as the aberrant expression of synaptic proteins (e.g., NR2A and NR2B), abnormal neuronal plasticity-related signaling pathways (e.g., PKA and GSK3β), and detrimental elevation in astrocytic A2AR expression in the hippocampus and cortex of APP/PS1 mice. In conclusion, our findings suggest that modulation of adenosine homeostasis by J4 is beneficial in a mouse model of AD. Our study provides a potential therapeutic strategy to delay the progression of AD.
Databáze: OpenAIRE
Externí odkaz: