Neuroprotection by Caffeine and A2A Adenosine Receptor Inactivation in a Model of Parkinson's Disease

Coffee consumption is linked to neuroprotective effects, but energy drinks do not necessarily produce the same effects.

In mice treated with a toxin that mimics Parkinson's disease, daily caffeine at a specific dose prevents a 2.5-fold loss of dopamine in a brain region critical for movement, and this protection is linked to the blocking of adenosine A2A receptors.

In mice, removing the adenosine A2A receptor results in four times more dopamine remaining in the striatum after exposure to MPTP, compared to mice with the receptor intact.

In mice exposed to a neurotoxin, caffeine protects nerve cells and improves movement, and these effects disappear when the A2A receptor is genetically removed, showing that the A2A receptor is necessary for both outcomes.

In mice, blocking adenosine A2A receptors with specific drugs reduces dopamine loss caused by the neurotoxin MPTP, while blocking adenosine A1 receptors with another drug does not protect against dopamine loss and increases damage.

Caffeine and drugs that block A2A receptors do not change the concentration of the neurotoxin MPTP or its breakdown product MPDP in the striatum. The protective effect of these substances occurs after the toxin has entered brain cells, by changing how neurons signal, not by altering how the toxin is processed.