Brain Derived Neurotrophic Factor Deficiency is Associated with Cognitive Impairment and Elevated Phospholipase A2 Activity in Plasma of Mice.

Decreased levels of Brain-Derived Neurotrophic Factor (BDNF) are a common finding in schizophrenia. Another well-documented protein linked to schizophrenia is intracellular Ca2+-independent Phospholipase (PLA2). However, the potential association between PLA2 and BDNF with regard to schizophrenia has yet to be examined. In the present study, male and female BDNF knockout mice, a possible genetic model of schizophrenia, were exposed to prenatal stress and tested in the nest test, open field test and T-maze. Following behavioral tests, whole brain and plasma samples were harvested to measure the activity of PLA2. BDNF knockout mice showed cognitive deficits in the T-maze. Furthermore, there was a quadratic association of PLA2 with performance in the open field test. Moreover, BDNF deficiency and female sex were associated with elevated plasma PLA2 levels. The cognitive impairment of BDNF heterozygous mice as well as their increased PLA2 activity in plasma is consistent with findings in schizophrenia patients. The particular elevation of PLA2 activity in females may partly explain sex differences of clinical symptoms in schizophrenia (e.g. age of onset, severity of symptoms). Additionally, PLA2 was significantly correlated with body and adrenal weight after weaning, whereby the latter emphasizes the possible connection of PLA2 with steroidogenesis.

Tryptanthrin promotes keratinocyte and fibroblast responses in vitro after infection with Trichophyton benhamiae DSM6916.

Exceedingly virulent pathogens and growing antimicrobial resistances require new therapeutic approaches. The zoophilic dermatophyte Trichophyton benhamiae causes highly inflammatory, cutaneous fungal infections. Recently, it could be shown that the plant-derived alkaloid tryptanthrin (TRP) exhibits strong anti-microbial activities against yeasts and dermatophytes. The aim of this study was to analyse the bioactivity of TRP under infectious conditions using an in-vitro dermatophytosis model employing fibroblasts and keratinocytes infected with T. benhamiae DSM6916. Analyses comprised determination of cell viability, effects on the innate immune response including expression and secretion of pro-inflammatory cytokines/chemokines as well as expression of various antimicrobial peptides (AMP), toll-like receptor (TLR) 2 and proliferation marker MKI67. T. benhamiae caused severe inflammation in the cutaneous cell models. TRP almost fully prevented T. benhamiae-derived damage of dermal fibroblasts and substantially reduced it in epidermal keratinocytes. A distinct down-regulation of the expression and secretion of pro-inflammatory cytokines was observed. Further, TRP promoted AMP expression, especially of HBD2 and HBD3, in keratinocytes even without fungal presence. This study provides crucial evidence that TRP is not only a strong antifungal agent but also potentially modulates the innate immune response. This makes it interesting as a natural antimycotic drug for adjuvant treatment and prevention of fungal re-infection.