The stress susceptibility factor FKBP51 controls S-ketamine-evoked release of mBDNF in the prefrontal cortex of mice.

We report here the involvement of the stress-responsive glucocorticoid receptor co-chaperone FKBP51 in the mechanism of in vivo secretion of mature BDNF (mBDNF). We used a novel method combining brain microdialysis with a capillary electrophoresis-based immunoassay, to examine mBDNF secretion in the medial prefrontal cortex (mPFC) in vivo in freely moving mice. By combining optogenetic, neurochemical (KCl-evoked depolarization), and transgenic (conditional BDNF knockout mice) means, we have shown that the increase in extracellular mBDNF in vivo is determined by neuronal activity. Withal, mBDNF secretion in the mPFC of mice was stimulated by a systemic administration of S-ketamine (10 or 50 mg/kg) or S-hydroxynorketamine (10 mg/kg). KCl- and S-ketamine-evoked mBDNF secretion was strongly dependent on the expression of FKBP51. Moreover, the inability of S-ketamine to evoke a transient secretion in mBDNF in the mPFC in FKBP51- knockout mice matched the lack of antidepressant-like effect of S-ketamine in the tail suspension test. Our data reveal a critical role of FKBP51 in mBDNF secretion and suggest the involvement of mBDNF in the realization of immediate stress-coping behavior induced by acute S-ketamine.

Ultrastructural and immunological features of experimental cutaneous leishmaniasis after treatment with intralesional hypertonic sodium chloride and CO2 laser rays.

This study investigated the mechanism of action and efficacy of CO2 laser rays and hypertonic sodium chloride (NaCl) with different concentrations in treatment of cutaneous leishmaniasis (CL) as assessed clinically, parasitologically, histopathologically by light & transmission electron microscopy (TEM) and immunologically by RT-PCR for gene expression of interleukin-13 (IL-13). Eighty mice were divided into four groups. The first was non infected control group (n=16) and the second was infected and served as non-treated control (n=16). The third (n=32) and fourth groups (n=16) were subjected to NaCl injection and CO2 laser respectively. Results showed that clinical healing by CO2 laser were nearly similar to normal appearance, but differed according to concentration of NaCl, as confirmed by ultrastructure and immunohistopathologic features of the host cells and surrounding skin tissue. IL-13 mRNA was significantly decreased after treatment denoting that Th2 cytokine (IL-13) is important for the development of strategies to prevent the induction of pathologic processes. It is concluded that CO2 laser then 7% NaCl are good modalities for CL treatment and is recommended wherever possible.