HLDF-6-H Peptide Exhibits an Anti-inflammatory Effect in the Development of Depression in an MPTP Model of Parkinson's Disease

Abstract

In this work, we investigate the anti-inflammatory effect of the HLDF-6-H peptide (Thr-Gly-Glu-HseHis-Arg) in a model of the presymptomatic stage of Parkinson’s disease (PD). This peptide is a bioactive fragment of the HLDF leukocyte differentiation factor. The presymptomatic stage of PD was modelled by introducing moderate doses of MPTP toxin to C57Bl/6 mice. HLDF-6-H was administered intranasally at a dose of 300 μg/kg daily for three weeks. The severity of depression was determined by the time of immobilization in a Porsolt test. The serum levels of 10 steroids were determined using MS analysis. The activity of inflammatory markers leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) was determined using kinetic methods. The development of an inflammatory process under the influence of MPTP is evidenced by an increase in the activity of α1-PI; the anti-inflammatory effect of the peptide is manifested in a decreased activity of LE and α1-PI. At the same time, the immobilization time of mice in a Porsolt test positively correlated with α1-PI and LE, which may indicate the role of inflammation in the development of depression. A positive correlation between estradiol and LE was found in the general sample of mice. In the group of mice treated with the peptide, α1-PI correlated positively with corticosterone and negatively with estradiol and androstenedione. It can be assumed that the anti-inflammatory effect of the peptide is associated with the regulation of corticosteroids and sex hormones. Hence, the applied experimental model confirmed the development of a depressive-like syndrome and neuroendocrine disorders in the presymptomatic stage of PD. The long-term use of HLDF-6-H has antidepressant and anti-inflammatory effects.