Role for Astroglia-Derived BDNF and MSK1 in Homeostatic Synaptic Plasticity

Neuroglia

Frenguelli, Bruno G.¹  Moss, Guy W. J.²  Bogdanov, Alexander³  Lalo, Ulyana⁴ 

[1] Author to whom correspondence should be addressed;Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, UK;Institute for Chemistry and Biology, Immanuel Kant Baltic Federal University 2 Universitetskaya str., Kaliningrad 236040, Russia;School of Life Sciences, University of Warwick, Gibbet Hill Campus, Coventry CV4 7AL, UK

关键词: aging;    dendritic spines;    synaptic strength;    glia–neuron interactions;    ion conductance microscopy;    synaptic scaling;    diet;    enriched environment;    GABA receptors;    AMPA receptors;    TrkB receptors;    Arc/Arg3.1;    calcium signalling;   

DOI  :  10.3390/neuroglia1020026

学科分类：医学解剖学

来源: mdpi

【 摘 要 】

Homeostatic scaling of synaptic strength in response to environmental stimuli may underlie the beneficial effects of an active lifestyle on brain function. Our previous results highlighted a key role for brain-derived neurotrophic factor (BDNF) and mitogen- and stress-activated protein kinase 1 (MSK1) in experience-related homeostatic synaptic plasticity. Astroglia have recently been shown to serve as an important source of BDNF. To elucidate a role for astroglia-derived BDNF, we explored homeostatic synaptic plasticity in transgenic mice with an impairment in the BDNF/MSK1 pathway (MSK1 kinase dead knock-in (KD) mice) and impairment of glial exocytosis (dnSNARE mice). We observed that prolonged tonic activation of astrocytes caused BDNF-dependent upregulation of excitatory synaptic currents accompanied by enlargement of synaptic boutons. We found that exposure to environmental enrichment (EE) and caloric restriction (CR) strongly upregulated excitatory but downregulated inhibitory synaptic currents in old wild-type mice, thus counterbalancing the impact of ageing on synaptic transmission. In parallel, EE and CR enhanced astrocytic Ca2+-signalling. Importantly, we observed a significant deficit in the effects of EE and CR on synaptic transmission in the MSK1 KD and dnSNARE mice. Combined, our results strongly support the importance of astrocytic exocytosis of BDNF for the beneficial effects of EE and CR on synaptic transmission and plasticity in the ageing brain.

【 授权许可】

CC BY