Anxiety and depression: A matter of stiffness?

Cells react to stress by the universal responses of "fluidization" or "reinforcement" (stiffening) of the cytoplasm, through dramatic re-arrangements of the cytoskeleton. Here it is suggested that, at a supracellular level, the brain exhibits such a fundamental behavior as part of its complex response to stress: it is hypothesized that the soft gel formed by brain cell cytoskeletons and the surrounding extracellular matrix (the "cytoskeletons-matrix system") undergoes transitions either to sol (fluidization) or stiff gel (reinforcement) as a very fundamental and evolutionarily conserved brain response to stress, alongside more sophisticated neural pathways. Sol state corresponds to increased cell activity (a sort of "fight or flight" response), whereas stiff gel state corresponds to inactivity (an "immobility" strategy). Psychological stress, through simple stress signals such as pH changes, would lead to an initial tissue fluidization in key regions of the brain, followed, if the stress stimuli persist, by reinforcement (slow formation of actomyosin stress fibers and matrix stiffening). It is also hypothesized that the cytoskeletons-matrix system is one of the biological correlates of so-called "background feelings", i.e conscious feelings built on inner chemical-physical states of the body. Optimal dynamics of the cytoskeletons-matrix system would contribute to a core feeling of well-being, while shifts towards fluidization (activation) or stiffening (inactivation) would contribute to background feelings at the basis of anxiety and stress-induced depression, respectively. It is suggested that the cytoskeletons-matrix system behaves as a "self-organized critical system", anxiety and depression arising whenever the system is driven too far from the optimal critical point. Finally, some application hints from the proposed ideas are given.

Ultra-low-level laser therapy.

A growing number of laboratory and clinical studies over the past 10 years have shown that low-level laser stimulation (633 or 670 nm) at extremely low power densities (about 0.15 mW/cm(2)), when administered through a particular emission mode, is capable of eliciting significant biological effects. Studies on cell cultures and animal models as well as clinical trials give support to a novel therapeutic modality, which may be referred to as ultra low level laser therapy (ULLLT). In cultured neural cells, pulsed irradiation (670 nm, 0.45 mJ/cm(2)) has shown to stimulate NGF-induced neurite elongation and to protect cells against oxidative stress. In rats, anti-edema and anti-hyperalgesia effects following ULLL irradiation were found. Clinical studies have reported beneficial effects (also revealed through sonography) in the treatment of musculoskeletal disorders. The present paper reviews the existing experimental evidence available on ULLLT. Furthermore, the puzzling issue of the biophysical mechanisms that lie at the basis of the method is explored and some hypotheses are proposed. Besides presenting the state-of-the-art about this novel photobiostimulation therapy, the present paper aims to open up an interdisciplinary discussion and stimulate new research on this subject.

Mechanical signalling in tissues and its possible role in nociception.

Mechanotransduction is known to play a key role in physiological as well as pathological processes. In the present work, the possibility is discussed that even weak mechanical signals travelling through the extracellular matrix can elicit significant cellular responses, by causing gel/sol transitions and actomyosin contractions. Such mechanical cues can result from both physiological activities, such as the heartbeat, and noxious stimuli to which tissues respond by rearranging the cells' cytoskeleton and remodelling the extracellular matrix. The possibility is explored that such viscoelastic modifications also affect the function of nociceptors, thus modulating pain transmission. Growing evidence indicates that the rearrangement of the axonal cytoskeleton represents a key step in nociception. Hyperalgesia is suggested to result from an exceedingly dynamical state of the nociceptor's cytoskeleton, which would lead to enhanced electrical conduction and synaptic facilitation.

[Prebiotic phosphate: a problem insoluble in water ? ]. / Fosforo prebiotico: un problema insolubile in acqua?

It is well-known that in water phosphate readily reacts with calcium, precipitating as insoluble apatite. How phosphorus could have been available for prebiotic reactions is still an open problem. We suggest that phosphorus-containing compounds might have accumulated in a hydrophobic medium, since the absence of calcium ions would have prevented them from precipitating as apatite. Hydrophobic compounds may have been synthesized on the early Earth through the polymerization of methane or through Fischer-Tropsch-type reactions. Moreover, hydrophobic compounds would have been delivered to the early Earth by extraterrestrial infall. In previous articles (Morchio and Traverso [1999], Morchio et al. [2001]) we suggested that such hydrophobic material would have formed a hydrophobic layer on the surface of the sea, which would have provided an environment thermodynamically more suitable than water for the concentration and polymerization of organic molecules fundamental to life, particularly amino acids and (pyrimidine) bases. It may be hypothesized that elemental phosphorus or phosphorus-containing compounds (such as phosphite) deriving from volcanic eruptions would have ended up raining down into the hydrophobic layer, accumulating due to the absence of calcium ions, in an environment protected against hydrolysis. Phosphorus-containing compounds might have interacted with hydrophobic molecules in the layer giving rise to polymers. In particular, phosphite might have reacted with the hydrophobic amino acids, giving rise to phosphoamino acids, which, in turn, might have interacted with pyrimidine bases (relatively abundant in the layer) giving rise to peptides and oligonucleotide-like polymers. Indeed, it has been experimentally shown (Zhou et al. [1996]) that, in an anhydrous organic medium (pyridine), dialkilphosphite reacts with amino acids to form phosphoamino acids, which interact with pyrimidine nucleosides to give nucleotides, short oligonucleotides and phosphoryl peptides.