Serum Levels of Brain-Derived Neurotrophic Factor (BDNF), Tissue-Type Plasminogen Activator (tPA) and Its Inhibitor (PAI-1) in Children with Autism

Background:  Autism seems to be characterized by altered neuronal cytoarchitecture, synaptogenesis and possibly also cellular immune responses. Neurotrophic factors (NTFs) are central to many facets of the central nervous system (CNS) function, from differentiation and neuronal survival to synaptogenesis and activity-dependent forms of synaptic. BDNF belongs to the family of NTFs and it is active in the mammalian. Plasmin, a serine protease, is involved in many physiologically relevant processes, including haemostasis, cellular recruitment during immune response, tumour growth, and also neuronal migration and synaptic remodeling. Both tissue-type and urokinase-type plasminogen activators can be efficiently inhibited by plasminogen activator inhibitor-1 (PAI-1), a protease inhibitor of serpin family. Tissue plasminogen activator (tPA or PLAT), is found not only in the blood, where it seems as a thrombolytic enzyme, but also in CNS. Studies in the recent decades have shown that tPA may play an important role in the pathogenesis of mental development disorder. So, all of the BDNF, tPA and PAI-1 activities are essential for the hippocampus functions in the autism children.

Objectives:  The aim of this study was to investigate the concentrations of BDNF, tPA and PAI-1 levels in children with autism.

Methods:  Participants included 93 autistic individuals meeting DSM - Ⅳcriteria( 83 boys, 10 girls; ages 2 to 10), and 99 age- and sex-matched healthy children(90 boys and 9 girls; ages 3 to 9)selected from a local public kindergarten and used as a controls group. According to the Childhood Autism Rating Scale (CARS), children with autism were graded for the illness severity. Levels of cytokines in serum were quantified by an enzyme-linked immunosorbent.

Results:  Serum BDNF levels in children with autism were 28.49±1101 pg/ml, and significantly higher than those in the normal subjects (21.32±11.12 pg/ml; t=3.42, p=0.001). Serum PAI-1 levels (1316.43±593.86 ng/ml) in the children with autism were also significantly higher compared with children with normal development (592.51±502.19 ng/ml; t=5.72, p=0.000). On the other hand, serum tPA values (805.47±436.38pg/ml) in children with autism were significantly lower compared with control children (1103.85±562.29 pg/ml; t=2.56, p=0.012).

Conclusions:  Serum levels of BDNF, tPA and PAI-1 may be associated with the disease of autism. Focusing on the NTFs, the puzzling aetiology of these cytokines should be further elucidated for the children with autism in the future.