Neuroprotective Effects of C-Phycocyanin in Chronic Unpredictable Mild Stress-Exposed Rats: Regulation of Neuroinflammation and CREB/BDNF Signaling

Abstract

Depression is a widespread neuropsychiatric disorder that significantly impacts emotional and cognitive function. Antidepressant medications are frequently accompanied by various adverse effects. C-phycocyanin has been previously shown to exert potent anti-inflammatory, and neuroprotective properties. Therefore, this study evaluated the therapeutic effects of C-phycocyanin against anxiety and depressive-like behaviors, and memory dysfunction in an animal model of chronic unpredictable mild stress (CUMS)-induced depression and explored the underlying mechanisms. Rats were daily exposed for six weeks to CUMS, during which phycocyanin (100 mg/kg, orally) was administered in the final three weeks of the study. Following the assessment of anxiety/ depressive-like behaviors, and memory dysfunction by the open field test (OFT), tail suspension test (TST), elevated plus maze (EPM), and passive avoidance test (PAT), rats were euthanized by decapitation. Then, hippocampal TNF-alpha and IL-1 beta concentrations, and hippocampal protein expressions (Iba-1, CD86, NF-kappa beta, CREB, and BDNF) were determined by an ELISA assay, and western blots, respectively. C-phycocyanin significantly decreased immobility time in OFT and TST, increased open arm time in EPM, and step-through latency time in PAT. Furthermore, C-phycocyanin suppressed CUMS-induced the M1 microglia polarization and neuroinflammation by reducing hippocampal TNF-alpha and IL-1 beta concentrations, and the protein expression of Iba-1, CD86, and NF-kappa beta in the hippocampus of CUMS-exposed rats. It also increased the hippocampal protein expression of CREB and BDNF. C-phycocyanin improved CUMS-induced anxiety and depressive-like behaviors, and memory dysfunction, which could be explained, at least in part, by inhibition of M1 microglial polarization and neuroinflammation, and enhancement of CREB/BDNF signaling.