Interleukin-10 and transforming growth factor-b1 facilitate long-term potentiation in CA1 region of hippocampus Miroslav N. Nenov a, b, * , Anton E. Malkov a , Maxim V. Konakov a , Sergey G. Levin a a Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia b Alzheimer's Center at Temple, Lewis Katz School of Medicine, Temple University, Philadelphia, PA,19140, USA article info Article history: Received 23 July 2019 Accepted 12 August 2019 Available online xxx Keywords: Anti-inflammatory cytokines Interleukine-10 Transforming growth factor-b1 Long-term potentiation Synaptic plasticity abstract It has been shown that pro-inflammatory cytokines preferentially attenuate long-term potentiation (LTP), at the same time the effect of anti-inflammatory cytokines on synaptic plasticity has not been fully studied yet. Here we studied the effect of two anti-inflammatory cytokines - interleukin-10 (IL-10) and transforming growth factor-b1 (TGF-b1) on long-term potentiation. It was found that exogenously added IL-10 as well as TGF-b1 were able to effectively facilitate LTP evoked with ether high frequency or theta burst stimulation protocols in CA1 area of hippocampus. Effectiveness of IL-10 and TGF-b1 on LTP varied depending on the concentration of used cytokine and type of tetanic stimulation protocol used for LTP induction. Overall the positive effect of studied cytokines on LTP was associated with their ability to increase basal synaptic strength at Schaffer collateral e CA1 synapse. At the same time IL-10 and TGF-b1 did not have any effect on short-term plasticity. Our results provide new evidence upon the modulatory effects that anti-inflammatory cytokines exert on synaptic plasticity further highlighting their potency as modulators of neuronal function. © 2019 Elsevier Inc. All rights reserved. 1. Introduction Growing evidence supports the involvement of anti- inflammatory cytokines such as interleukin 10 (IL-10) and trans- forming growth factor-b1 (TGF-b1) as modulators of brain function at different pathophysiological conditions [1e3]. In particular, it has been shown that exogenously added IL-10 or TGF-b1 can exert neuroprotective effects preventing neuronal hyperexcitability and subsequent neuronal damage in pathophysiological conditions associated with hypoxia/ischemia [4,5]. It was found that IL-10 and TGF-b1 regulate neuronal excitability and synaptic plasticity by modulating the activity of different ion channels including AMPA and NMDA receptors that are critical for synaptic plasticity and memory formation [6e8]. Recently it has been shown that besides being a part of the neuro-inflammatory response, IL-10 and TGF-b1 can regulate neuronal activity at normal physiological conditions by modulating glutamatergic and GABAergic synaptic activity [9e11]. However, the exact role of anti-inflammatory cytokines in regulation of synaptic plasticity and neuronal network activity associated with normal brain function is still not well studied. Here, we aimed to study whether exogenous IL-10 and TGF-b1 can modulate synaptic plasticity under normal experimental conditions using two different paradigms in order to induce long-term potentiation in CA1 area of rat hippocampus e high frequency and theta-burst stimulation protocols, HFS and TBS respectively. Next, basal syn- aptic strength and short-term plasticity were studied for their contribution to the cytokines effect on LTP. 2. Material and methods 2.1. Slice preparation All experiments were carried out with male Wistar rats (7e8 weeks old; total n ¼ 78). The use of animals was in accordance with the European Communities Council Directive (86/609/EEC) and approved by bioethical committee of Institute of Theoretical and Experimental Biophysics of Russian Academy of Sciences. After acute decapitation brain was extracted and placed to 4  C chilled and bubbled with carbogen gas mixture (95%O 2 /5%CO 2 ) artificial cerebrospinal fluid (aCSF) of the following composition: 126 mM * Corresponding author. Alzheimer's Center at Temple, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 19140, USA. E-mail addresses: nenovmir@gmail.com, miroslav.nenov@temple.edu (M.N. Nenov). Contents lists available at ScienceDirect Biochemical and Biophysical Research Communications journal homepage: www.elsevier.com/locate/ybbrc https://doi.org/10.1016/j.bbrc.2019.08.072 0006-291X/© 2019 Elsevier Inc. All rights reserved. Biochemical and Biophysical Research Communications xxx (xxxx) xxx Please cite this article as: M.N. Nenov et al., Interleukin-10 and transforming growth factor-b1 facilitate long-term potentiation in CA1 region of hippocampus, Biochemical and Biophysical Research Communications, https://doi.org/10.1016/j.bbrc.2019.08.072