Animal brain uptake studies

Whether it is possible to raise carnosine levels in human brain is unknown. One study in rats has shown that oral administration of chicken extract (a major source of carnosine in humans too) did provoke an increase in brain carnosine levels a single dose of the chicken extract led to an increase in carnosine levels within 30 min in plasma, but 1 or 2 h duration were required for increased levels of carnosine to be observed in the cerebral cortex, hypthalamus, and hippocampus (Tomonaga et ah, 2007). It is uncertain whether these effects result from direct uptake of the carnosine from plasma or a consequence of de novo synthesis. In a study using senescence-accelerated mice (SAMP8), it was found that oral supplementation with creatine provoked, at 25 weeks of age, a transient 88% increase in muscle carnosine content, accompanied by a 40% increase in anserine content, which coincided with an improvement in resistance to contractile fatigue (Derave et ah, 2008). At 60 weeks, no differences were detectable between the creatine-supplemented and control animals in terms of their muscle... 

In vivo microdialysis is a technique that allows sampling of extracellular levels of neurotransmitters in discrete regions of the brain. The extracellular neurotransmitter levels provide an indication of the net activity of a particular set of neurons, including release, synthesis, and uptake, from conscious unanesthetized animals. For example, in vivo microdialysis studies have shown that extracellular 5-HT levels measured under appropriate conditions are dependent on the concentration of Ca2+ or K+ in the perfusion fluid, is inhibited by tetrodotoxin, and is predominately neuronal in origin (45). In addition, specific neural processes can be measured after the local application of agents through the microdialysis probe, such as release after application of hypertonic KC1, rate of synthesis after synthesis inhibitors, or the local effects of drugs (46). This technique has made it possible to more accurately quantitate and characterize the... 

It is interesting to notice that the characterization of the cellular and molecular mechanisms of the star fruit intoxication needs to pass through a group of different experimental protocols among them in vivo and the in vitro bioassays. The correlation between in vivo and in vitro models is then more complex that we should think it is [53]. Thus, the particular case of synaptosomes and GABA and glutamate release and re-uptake, shows neurochemical dynamics associated to star fruit intoxication mechanisms in a preparation which consists of isolated synaptic terminals (44). However, additional studies are needed with brain slices from control brains treated with the AcTx and even the use of ex vivo models in vitro bioassays from tissue after in vivo experiments), for example, in our case, brain slices from treated animals. 

---