¹Aarhus University, Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus, Denmark, ²Aarhus University, Department of Infectious Disease, Aarhus, Denmark

Background: Background: Chemotherapy causes severe sickness (CIS) and cognitive disturbances (chemo-brain) in up to 75% of the patients receiving this treatment. The adverse effects are believed to be caused in part by an imbalance of pro- and anti-inflammatory cytokines and the microbiota has also been shown to modulate the efficacy and toxicity of chemotherapy. Parasitic worms (helminths) can reduce inflammation, restore the gut barrier, and beneficially modulate the host microbiota.

Aims & Objectives: The objective of this project is two-fold: 1) to examine the protective effects of helminth derived molecules (TSP) on CIS and cognitive deficits, and 2) to explore the underlying biological mechanisms normalised by helminths. We hypothesize that the beneficial effects of the helminths are caused by a reduction of neuroinflammation mediated by the microbiota.

Method: Male S-D rats (n=10/group) are treated weekly for 4 weeks with TSP and/or the chemotherapy drug Doxorubicin (DOX). Throughout the treatment, the animals are housed in Noldus Phenotyper cages and spontaneous behaviour and bodyweight is monitored. Following the treatment period, the animals undergo a behavioural test battery and subsequently neuroinflammation and neurotransmitter alterations are examined using Ella, immunohistochemistry and HPLC. Data is analysed using 2 x 2 ANOVAs. Non-normally distributed data are ln-transformed.

Results: Pretreatment with TSP reduced weight loss following DOX treatment as compared to controls. Furthermore, TSP prevented DOX induced memory deficits in the novel object recognition test (p<0.05). Pilot experiments have also showed increased expression of antiinflammatory cytokines, a tendency for reduced microgliosis by TSP and an increased turnover of 5-HT by DOX which was reversed by TSP.

Discussion & Conclusions: TSP is a promising candidate for treatment of chemotherapy-induced side-effects, possibly through a modulation of the microbiota leading to a reversal of neuroinflammation and normalisation of 5-HT metabolism.