Effects of chronic caffeine intake in a mouse model of amyotrophic lateral sclerosis

Abstract

Caffeine is a nonselective adenosine receptor antagonist; chronic consumption has proved protective toward neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. The present study was designed to determine whether caffeine intake affected survival and/or motor performance in a transgenic model of amyotrophic lateral sclerosis (ALS). SOD1(G93A) mice received caffeine through drinking water from 70 days of age until death. Body weight, motor performance and survival were evaluated. Furthermore, the expression of adenosine A(2A) receptors (A(2A) Rs), glial glutamate transporter (GLT1), and glial fibrillar acidic protein (GFAP) were evaluated by Western blotting. The results showed that caffeine intake significantly shortened the survival of SOD1(G93A) mice (log rank test, P = 0.01) and induced a nonsignificant advancing of disease onset. The expression of A(2A) R, GLT1, and GFAP was altered in the spinal cords of ALS mice, but caffeine did not influence their expression in either wild-type or SOD1(G93) mice. These data indicate that adenosine receptors may play an important role in ALS.

Adenosine A2A Receptors Activation Facilitates Neuromuscular Transmission in the Pre-Symptomatic Phase of the SOD1(G93A) ALS Mice, but Not in the Symptomatic Phase

“…A 2A receptors are overexpressed in lymphocytes from ALS patients, resulting in increased levels of intracellular cAMP [51], which highlights a possible role for these receptors in immunosuppressive responses in ALS. Whether the now documented A 2A receptor functional changes in the SOD1(G93A) also parallel with an immunological based response and relate with the previously reported A 2A receptor-mediated delayed onset and reduced progression of motor neuron dysfunction in this ALS model [11], awaits further investigation.…”

“…A 2A receptors expression was shown to be decreased in the spinal cord of symptomatic SOD1(G93A) animals [11]. Alterations in the transducing system operated by A 2A receptors may also be altered in ALS.…”

“…A 2A receptors are known to have a neuroprotective role in some pathological conditions [8] and have been considered as a potential therapeutical target for ALS [10]–[12]. Some contradictory reports in the literature can however be found [10], [11] highlighting the need for an evaluation of the influence of A 2A receptors in ALS models where disease progression and neuromuscular transmission impairment can be taken into account.…”

Suppression of adenosine 2a receptor (A2aR)-mediated adenosine signaling improves disease phenotypes in a mouse model of amyotrophic lateral sclerosis

“…Although our observation indicates that the A 2a R expression is altered at the symptomatic stage, the specific disease stages from which the A 2a R signaling is altered in SOD1G93A mice likely resulted from different regions examined in our study and the previous study (Nascimento et al, 2014). Although chronic administration of caffeine, a non-specific antagonist of all adenosine receptors, significantly shortens overall survival of SOD1G93A mice without obvious effect on the body weight and motor phenotypes (Potenza et al, 2013), this likely resulted from the pan-inhibition of all adenosine receptors, especially the neuroprotective A 1 R.…”

Intakes of caffeine, coffee and tea and risk of amyotrophic lateral sclerosis: Results from five cohort studies

“…Although caffeine has neuroprotective effects in animal models of Parkinson's Disease (7), in the only published study in animal models of ALS, caffeine administration was reported to accelerate disease progression and shorten survival in SOD1 mice (29). The results of both epidemiological and experimental studies, therefore, unfortunately suggest that caffeine consumption does not have beneficial effects in the disease process that leads to ALS.…”