Study showing caffeine’s effects on human cortical networks in Frontiers in Pharmacology

INF PhD student Amber Kerkhofs and PI Huib Mansvelder, together with their collaborators in Portugal, present a first characterization of the restorative capacity of caffeine on synaptic transmission and neuronal excitability in the human cortex. The paper was published on the 4th of January in Frontiers in Pharmacology.

Caffeine is consumed all over the world and as such it sits together with alcohol and nicotine at the top of the most widely consumed psycho-active drugs. There is quite a bit of knowledge about the positive effects of caffeine or coffee on human behavior such as attention and alertness. However, very little was known regarding the effect of caffeine in doses of normal consumption on human cortical signaling. Collaborator Rodrigo A. Cunha, professor at the University of Coimbra: “It is very important to understand the effect of realistic concentration of caffeine, as caffeine is only a psychostimulant with neuroprotective actions at moderate doses, but is a depressant with deleterious effects at higher doses”.

The research was conducted on human neocortical tissue derived from epileptic patients that underwent surgery for treatment of deeper brain structures. “Using human samples for research on the effect of psycho-active substances is increasingly important, as over the years we have learned that the human brain is not just an upscaled version of the rodent brain. Using human samples to expand previous knowledge from functional research in rodents is therefore of paramount importance to understand the effect of these substances on the human brain and their effect on human behaviour”, says professor Huib Mansvelder.

The main finding of these researchers was that caffeine has strong positive effects on synaptic transmission and pyramidal neuron excitability when brain cells were artificially made "tired" by adding adenosine, a signaling molecule that slows down brain activity. First author Amber Kerkhofs: "This finding exactly confirms an intuitive feeling on the role of caffeine: similar to how drinking coffee helps us humans fight tiredness, having caffeine around helps cells preventing the slowdown of cellular communication”.

Whereas in earlier research in rodents caffeine mainly affected presynaptic signaling, in the human cortex caffeine mainly affected postsynaptic signaling. “The human cortex thus responds differently to caffeine than the cortex of mice and rats, animals normally used for this kind of research. This shows that although the human and rodent brain rely mainly on similar mechanisms, small differences can have a large impact on the overall effect. This stresses the importance of doing this work in slices from the human cortex”, Huib comments.

The collaboration with Portugal was important for the outcome of this research, as the group of Rodrigo Cunha has obtained extensive knowledge for over 20 years on the therapeutic effects of caffeine. Rodrigo Cunha: “Off course, these results do not directly lead to treating caffeine as a new medicine. However, this first neurophysiological description of the impact of caffeine on excitatory synaptic transmission in the human temporal cortex does provide an adequate ground for understanding the effects of caffeine in normal consumption amounts on cognition in humans. Amber Kerkhofs adds: “This bit of knowledge makes my daily cup of coffee taste a lot better”!

Caffeine Controls Glutamatergic Synaptic Transmission and Pyramidal Neuron Excitability in Human Neocortex can be found here.

Front. Pharmacol., 04 January 2018 |