α-lipoic acid and Propolis shield against lipopolysaccharide-induced behavioral deficits, depression and neuro-inflammation via regulating GR7M/BDNF/Homer/PI3K signaling pathways in rat model

Abstract

Abstract Copious pharmacological agents targeting monoamine neurotransmission merit the management of mental illnesses nevertheless, they possess concomitant side effects. Regulating BDNF/PI3K/GR7M/AKT/Homer pathways may constitute a vital signaling center in the subcellular integration of the synaptic neurotransmission. These pathways similarly modulate neuronal cell proliferation, plasticity and migration. As enzymes involved in cell survival and neuroplasticity are relevant to neurotrophic factor deregulation, the brain-derived neurotrophic (BDNF), Metabotropic glutamate receptor type 7 (GRM7), Phosphoinisitol kinase- 3 (PIK3), Serine/Threonine Kinase 1 (AKT), and Homer1 may afford an important signaling for neuro-protection in depression. This article summarized the involvement of PI3K/AKT/GR7M/BDNF/ Homer pathways in cell signaling of neuronal cells in mental illnesses. Depression has been identified as a ubiquitous and severe psychiatric mood neurobehavioral disorder. Neuro-inflammation and AKT/PI3K activation are known to be involved in the pathology of depression. The present study aimed to investigate the therapeutic index and potential mechanism of α-lipoic acid, Burdock and propolis in the lipopolysaccharide (LPS)-induced depression in rat model. α-lipoic acid, Burdock and propolis were injected orally, for 1 month post LPS injection daily. RNA gene expression of BDNF/PI3K/GR7M/AKT/Homer-1 was investigated. In results, α-lipoic acid, Burdock and propolis treatment exerted preventive effects versus LPS-induced depression. The aforementioned treatments increased the expression of PI3K/AKT/GR7M/Homer1 but decreased the ROS generation levels and reduced the expression of BDNF in LPS-induced depressive behavior in rats. In conclusion: These findings suggested that α-lipoic acid, Burdock and propolis exerted a preventive effect via GRM7/BDNF/AKT/PI3K signaling pathways in LPS-induced depressive behavior in rats.