Another possibility that could explain the subthreshold effect on cognition is associated with changes in carnosinase activity as the enzyme has been found to undergo an age-dependent enhanced activity in brains of aging individuals and AD patients. Finally, it is also possible that a more robust effect could be revealed by extending these behavioural studies to a larger cohort of animals. In summary, carnosine has a strong effect in restoring mitochondrial functioning and in counteracting amyloid pathology but these activities do not translate in a robust effect on cognition. These results suggest that, at least in complex AD animal models, addressing mitochondrial dysfunction and Ab aggregation without a parallel intervention on h-tau deposition is not sufficient to promote major beneficial cognitive effects. Supporting this idea, recent reports have in fact GDC-0199 1257044-40-8 indicated that therapeutic measures addressing Ab overloads but unable to reduce the development of tau pathology do not prevent the development of cognitive deficits in 3xTg AD mice. Recently, cell therapy has been proposed as an efficient method for regenerating injured nerves. Transplantation of Schwann cells or stem cells of various origins, which differentiate towards Schwann cell-like phenotype, stimulate peripheral nerve repair. Transplanted cells stimulate the growth and myelination of nerve sprouts by secreting neurotrophins and neuroregulins together with components of myelin shell. However, obtaining Schwann cells for autologous transplantation is highly traumatic and these cells are difficult to expand in vitro. Therefore, there is a need for a more easily accessible source of cells that are capable of stimulating nerve sprout growth and repair. Adipose-derived stem cells can be easily obtained and expanded in vitro for use in autologous cell therapy. Thus, transplanted ASCs stimulate blood vessel growth in vivo. This effect is dependent on the secretion of growth factors, VEGF, HGF and bFGF, and enhanced by exposing the cells to hypoxia. The ability of ASCs to stimulate the growth of nerve sprouts in ischemic myocardium has recently been demonstrated. Furthermore, nerve conduits seeded with ASCs differentiated towards Schwann-like cell phenotype and promote peripheral nerve repair. However, mechanisms of ASC‘s action on nerve regeneration are only partially understood. This can be addressed using in vivo models of nerve injury and growth in conjunction with determining gene expression patterns in the cells. In this study we tested the hypothesis that ASCs stimulate repair of crushed peripheral nerves and induce nerve sprout growth by producing neurotrophic growth factors as well as myelin sheath components. Since the ability of ASCs to prevent hypoxia-induced brain injury is dependent on BDNF production, we also examined the impact of this neurotrophin on nerve fiber growth induced by ASCs.