Effects of Bromelain in Maternal Deprivation and Social Isolation Models of Schizophrenia in Male BALB/c Mice

Abstract

Bromelain is a mixture of enzymes found in several parts of the pineapple plant, including the stem, fruit, leaves, and peel. Its use was recommended to slow down the progression of neurological disorders such as Parkinson’s disease. Although studies have examined the beneficial effects of bromelain (Br) in neurological disorders, its detailed benefits in schizophrenia are still poorly understood. We, thus, modeled schizophrenia using two developmental methods. In the first experiment, postweaning social isolation (SI) method where male mice were weaned at postnatal day (PND) 21 and isolated in individual cage for 5 weeks was used to induce schizophrenia. The second experiment used a maternal deprivation (MD) model, where mothers were separated from their pups for 24 h at PND 9. In both experiments 1 and 2, Br was administered orally from PND 21 to PND 56. At PND 56, there were behavioral assessments of nest building, anxiety, depression, and locomotion, while oxidative stress, neuroinflammation, brain-derived neurotrophic factor, and astrocyte expression in the prefrontal cortex and hippocampus were assessed at the end of the behavioral studies. Our study found that both SI and MD caused anxiety, depression, and hyperlocomotion. This was accompanied by oxidative stress in the prefrontal cortex and hippocampus, and neuroinflammation was observed only in the hippocampus. While SI rearing caused poor nest-building capacity, MD rearing did not impact nest-building capacity of the mice. The study found that administration of 50 mg/kg of Br reversed oxidative stress and neuroinflammation and significantly reduced anxiety level, hyperlocomotion, and depression in the mice. Mice administered Br also had a better nest-building capacity. Br may, therefore, benefit individuals at ultra-high risk and patients with schizophrenia, alleviating the positive, negative, and cognitive symptoms of the disease, without the side effects reported in the use of psychotic drugs.