Neuromodulation and neuroprotective effects of chlorogenic acids in excitatory synapses of mouse hippocampal slices

The increased healthspan afforded by coffee intake provides novel opportunities to identify new therapeutic strategies. Caffeine has been proposed to afford benefits through adenosine A2A receptors, which can control synaptic dysfunction underlying some brain disease. However, decaffeinated coffee and other main components of coffee such as chlorogenic acids, also attenuate brain dysfunction, although it is unknown if they control synaptic function. We now used electrophysiological recordings in mouse hippocampal slices to test if realistic concentrations of chlorogenic acids directly affect synaptic transmission and plasticity. 3-(3,4-dihydroxycinnamoyl)quinic acid (CA, 1–10 μM) and 5-O-(trans-3,4-dihydroxycinnamoyl)-D-quinic acid (NCA, 1–10 μM) were devoid of effect on synaptic transmission, paired-pulse facilitation or long-term potentiation (LTP) and long-term depression (LTD) in Schaffer collaterals-CA1 pyramidal synapses. However, CA and NCA increased the recovery of synaptic transmission upon re-oxygenation following 7 min of oxygen/glucose deprivation, an in vitro ischemia model. Also, CA and NCA attenuated the shift of LTD into LTP observed in hippocampal slices from animals with hippocampal-dependent memory deterioration after exposure to β-amyloid 1–42 (2 nmol, icv), in the context of Alzheimer’s disease. These findings show that chlorogenic acids do not directly affect synaptic transmission and plasticity but can indirectly affect other cellular targets to correct synaptic dysfunction. Unraveling the molecular mechanisms of action of chlorogenic acids will allow the design of hitherto unrecognized novel neuroprotective strategies

Effect of 6 weeks of swimming training on lactate threshold, time to exhaustion, and body weight.

<p>(A–C) Values are mean ±SEM (n = 14). Means without a common letter differ, p<0.05.</p

MnSOD activity, TBARS and protein carbonyls levels both after 6 weeks of swimming training and an exhaustive protocol test.

<p>(A–C) Values are mean ±SEM (n = 7). Means without a common letter differ, p<0.05. MnSOD: manganese superoxide dismutase; TBARS: thiobarbituric acid reactive substances; DNPH: dinitrophenylhydrazine.</p

GSH, GSSG, and GSH/GSSG ratio levels both after 6 weeks of swimming training and an exhaustive protocol test.

<p>(A–C) Values are mean ± SEM (n = 7). Means without a common letter differ, p<0.05. GSH: reduced glutathione; GSSG: oxidized glutathione.</p

MTT reduction and membrane potential, and ROS production both after 6 weeks of swimming training and an exhaustive protocol test.

<p>(A–C) Values are mean ±SEM (n = 7). Means without a common letter differ, p<0.05. ROS: reactive oxygen species; MTT: Methyl-tetrazolium; DCF-oxid: oxidized dichlorofluorescein diacetate; <i>Δψ</i>: membrane potential.</p

Timeline of the swimming training schedule and exhaustive protocol test data collection.

<p>Timeline of the swimming training schedule and exhaustive protocol test data collection.</p