Figure 3. Schematic hypothetical representation of the possible effects of bed rest and CCT on BDNF release. (A) Bed rest (BR) might act as a low-frequency stimulus inducing, at pre-synaptical level, the transcription of p75NTR, TrkB and proBDNF, which is proteolytically converted in BDNF. Thus, in the synaptical space might be released a high amount of mature BDNF and a low amount of proBDNF; both at post-synaptical and at pre-synaptical level, these molecules bind their specific receptors. BDNF binds to TrkB; at pre-synaptical level this induces the activation of MAPK pathway which, in turn, maintains active the transcription of BDNF. ProBDNF binds minimally to TrkB and principally to p75NTR; its activation at pre-synaptical level, via PIP2 pathway, leads to the suppression of BDNF transcription. Since BDNF amount is higher than proBDNF, the final balanced effect might be the persistant BDNF transcription and activity. This mechanism could be responsible for an increase of BDNF level in synaptic space and consequently in circulation. (B) CCT, acting as an high frequency stimulus, might be responsible for blocking the maturation of BDNF, leading to the release of high amounts of proBDNF and low amounts of BDNF in the synaptic space. In this case proBDNF modulatory effect might prevail on BDNF’s leading, in turn, to the suppression of the transcription of BDNF. In this case a rapid and transient increase of BDNF in the synaptic space and in circulation might occur.