Alpha-lactalbumin protects against pentylenetetrazole-induced seizures in mice reducing intestinal inflammation

Purpose: ?-Lactalbumin (ALAC) is the major protein component of bovine milk and possesses many pharmacological functions such as antioxidant, hypolipidemic, hypoallergenic and antitumorigenic. It was previously reported that ALAC exerts significant protective activity against seizures in animal models and part of its effects are mediated by the inhibition of NMDA receptors through the glycine binding site [1,2]. Recently, several studies have shown a bidirectional communication between the brain and the gut microbiota. Aim of this study was to evaluate whether ALAC would be able to reduce intestinal inflammation induced by dextran sulphate sodium (DSS) and if this action could reduce seizures in the pentylenetetrazole (PTZ) model in BALB/c mice. Method: Colitis was induced in mice by administering DSS (4%, wt:vol) in drinking water ad libitum for 6 days, followed by DSS-free water up to day 13. Drug treatments as follow were started at day 3: ALAC (375 mg/kg), Valproic Acid (600 mg/kg), Sodium Butyrate (100 mg/kg) and Mesalazine (15mg/kg). On day 14th, mice were tested for PTZ susceptibility and samples were collected for intestinal analysis of inflammation and damage. Results: ALAC treatment reduced colitis symptoms and colon damage and significantly decreased polymorphonuclear cell infiltration scores compared to the DSS group and other groups and in western blot analysis there was a reduction of inflammatory markers (COX-2, iNOS and NF?B). Moreover, ALAC treatment restores levels of propionic and butyric acid in stool samples. DSS-dependent intestinal inflammation significantly decreases PTZ seizure threshold and ALAC treatment completely prevents this phenomenon. Conclusion: Our data support the concept that intestinal inflammation can predispose to seizures and that ALAC, improving intestinal inflammation, has antiepileptic effects also through this mechanism.