The p75 neurotrophin receptor (p75NTR) is a transmembrane protein that binds nerve growth factor (NGF) and has multiple functions in the nervous system where it is expressed widely during the developmental stages of life, although expression decreases dramatically by adulthood. Expression of p75NTR can increase in pathological states related to neural cell death. p75NTR is a member of the tumour necrosis factor (TNF) receptor family and it consists of intracellular, transmembrane and extracellular domains which are different from other TNF receptors. Either by interacting with tropomyosin receptor kinase (Trk) receptors or via the independent binding of neurotrophin, p75NTR can induce neurite outgrowth and cellular survival or cell apoptosis through several complicated signal transduction pathways. Most of these signalling pathways remain to be elucidated. By interacting with different cellular factors, p75NTR can induce neuron growth cone collapse or regrowth. p75NTR is also expressed in a variety of glial populations. The many functions of p75NTR require further study.

Hydroxychloroquine (HCQ), which has been proposed as a therapeutic or prophylactic drug for SARS-COV-2, has been administered to thousands of individuals with varying efficacy; however, our understanding of its adverse effects is insufficient. It was reported that HCQ induced psychiatric symptoms in a few patients with autoimmune diseases, but it is still uncertain whether HCQ poses a risk to mental health. Therefore, in this study, we treated healthy mice with two different doses of HCQ that are comparable to clinically administered doses for 7 days. Psychiatric-like behaviors and the expression of related molecules in the brain were evaluated at two time points, i.e., 24 h and 10 days after drug administration. We found that HCQ increased anxiety behavior at both 24 h and 10 days and enhanced depressive behavior at 24 h. Furthermore, HCQ decreased the mRNA expression of interleukin-1beta and corticotropin-releasing hormone (Crh) in the hippocampus and decreased the mRNA expression of brain-derived neurotrophic factor (Bdnf) in both the hippocampus and amygdala. Most of these behavioral and molecular changes were sustained beyond 10 days after drug administration, and some of them were dose-dependent. Although this animal study does not prove that HCQ has a similar effect in humans, it indicates that HCQ poses a significant risk to mental health and suggests that further clinical investigation is essential. According to our data, we recommend that HCQ be carefully used as a prophylactic drug in people who are susceptible to mental disorders.