Depression is a common and severe neuropsychiatric disorder that is one of the leading causes of global disease burden. Although various anti-depressants are currently available, their efficacies are barely adequate and many have side effects. Hericium erinaceus, also known as Lion’s mane mushroom, has been shown to have various health benefits, including antioxidative, antidiabetic, anticancer, anti-inflammatory, antimicrobial, antihyperglycemic, and hypolipidemic effects. It has been used to treat cognitive impairment, Parkinson’s disease, and Alzheimer’s disease. Bioactive compounds extracted from the mycelia and fruiting bodies of H. erinaceus have been found to promote the expression of neurotrophic factors that are associated with cell proliferation such as nerve growth factors. Although antidepressant effects of H. erinaceus have not been validated and compared to the conventional antidepressants, based on the neurotrophic and neurogenic pathophysiology of depression, H. erinaceus may be a potential alternative medicine for the treatment of depression. This article critically reviews the current literature on the potential benefits of H. erinaceus as a treatment for depressive disorder as well as its mechanisms underlying the antidepressant-like activities.

Maladaptive changes in the carotid body (CB) induced by chronic intermittent hypoxia (IH) account for the pathogenesis of cardiovascular morbidity in patients with sleep-disordered breathing. We postulated that the proinflammatory cytokines, namely interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α, and cytokine receptors (IL-1r1, gp130 and TNFr1) locally expressed in the rat CB play a pathophysiological role in IH-induced CB inflammation. Results showed increased levels of oxidative stress (serum 8-isoprostane and nitrotyrosine in the CB) in rats with 7-day IH treatment resembling recurrent apneic conditions when compared with the normoxic control. Local inflammation shown by the amount of ED1-containing cells (macrophage infiltration) and the gene transcripts of NADPH oxidase subunits (gp91^phox and p22^phox) and chemokines (MCP-1, CCR2, MIP-1α, MIP-1β and ICAM-1) in the CB were significantly more in the hypoxic group than in the control. In addition, the cytokines and receptors were expressed in the lobules of chemosensitive glomus cells containing tyrosine hydroxylase and the levels of expressions were significantly increased in the hypoxic group. Exogenous cytokines elevated the intracellular calcium ([Ca²⁺]_i) response to acute hypoxia in the dissociated glomus cells. The effect of cytokines on the [Ca²⁺]_i response was significantly greater in the hypoxic than in the normoxic group. Moreover, daily treatment of IH rats with anti-inflammatory drugs (dexamethasone or ibuprofen) attenuated the levels of oxidative stress, gp91^phox expression and macrophage infiltration in the CB. Collectively, these results suggest that the upregulated expression of proinflammatory cytokine pathways could mediate the local inflammation and functional alteration of the CB under chronic IH conditions.

Chronic intermittent hypoxia (CIH) is a hallmark of obstructive sleep apnea (OSA), which induces hippocampal injuries mediated by oxidative stress. This study aims to examine the neuroprotective mechanism of Lycium barbarum polysaccharides (LBP) against CIH-induced spatial memory deficits. Adult Sprague–Dawley rats were exposed to hypoxic treatment resembling a severe OSA condition for a week. The animals were orally fed with LBP solution (1mg/kg) daily 2 hours prior to hypoxia or in air for the control. The effect of LBP on the spatial memory and levels of oxidative stress, inflammation, endoplasmic reticulum (ER) stress, apoptosis and neurogenesis in the hippocampus was examined. There was a significant deficit in the spatial memory and an elevated level of malondialdehyde with a decreased expression of antioxidant enzymes (SOD, GPx-1) in the hypoxic group when compared with the normoxic control. In addition, redox-sensitive nuclear factor kappa B (NFКB) canonical pathway was activated with a translocation of NFКB members (p65, p50) and increased expression levels of NFКB-dependent inflammatory cytokines and mediator (TNFα, IL-1β, COX-2); also, a significantly elevated level of ER stress (GRP78/Bip, PERK, CHOP) and autophagic flux in the hypoxic group, leading to neuronal apoptosis in hippocampal subfields (DG, CA1, CA3). Remarkably, LBP administration normalized the elevated level of oxidative stress, neuroinflammation, ER stress, autophagic flux and apoptosis induced by hypoxia. Moreover, LBP significantly mitigated both the caspase-dependent intrinsic (Bax, Bcl2, cytochrome C, cleaved caspase-3) and extrinsic (FADD, cleaved caspase-8, Bid) signaling apoptotic cascades. Furthermore, LBP administration prevented the spatial memory deficit and enhanced the hippocampal neurogenesis induced by hypoxia. Our results suggest that LBP is neuroprotective against CIH-induced hippocampal-dependent spatial memory deficits by promoting hippocampal neurogenesis and negatively modulating the apoptotic signaling cascades activated by oxidative stress and inflammation.

New Findings: What is the central question of this study?Expression of the renin–angiotensin system (RAS) may play a pathogenic role in the augmented activity of carotid body chemosensitive cells and the carotid body (CB) inflammation in chronic intermittent hypoxia (IH). The aim of this study was to examine the expression and function of the RAS components in the CB during chronic IH resembling a severe sleep‐apnoeic condition. What is the main finding and its importance?Chronic IH induces a functional upregulation of the RAS expression in the CB. The upregulation of RAS expression could play a pathogenic role in the augmented CB excitability during IH, which is relevant to early pathogenesis in sleep‐disordered breathing. The carotid body (CB) plays an important role in the alteration of cardiorespiratory activity in chronic intermittent hypoxia (IH) associated with sleep‐disordered breathing, which may be mediated by local expression of the renin–angiotensin system (RAS). We hypothesized a pathogenic role for IH‐induced RAS expression in the CB. The CB expression of RAS components was examined in rats exposed to IH resembling a severe sleep‐apnoeic condition for 7 days. In situ hybridization showed an elevated expression of angiotensinogen in the CB glomus cells in the hypoxic group when compared with the normoxic control group. Immunohistochemical studies and Western blot analysis revealed increases in the protein level of both angiotensinogen and angiotensin II type 1 (AT₁) receptors in the hypoxic group, which were localized to the glomic clusters containing tyrosine hydroxylase. RT‐PCR studies confirmed that levels of the mRNA expression of angiotensinogen, angiotensin‐converting enzyme, AT_1a and AT₂ receptors were significantly increased in the CBs of the hypoxic rats. Functionally, the [Ca²⁺]_i response to exogenous angiotensin II was enhanced in fura‐2‐loaded glomus cells dissociated from hypoxic rats when compared with those of the normoxic control animals. Pretreatment with losartan, but not PD123319, abolished the angiotensin II‐induced [Ca²⁺]_i response, suggesting an involvement of AT₁ receptors. Moreover, daily treatment of the IH group of rats with losartan attenuated the levels of oxidative stress, gp91^phox expression and macrophage infiltration in the CB. Collectively, the upregulated local RAS expression could play a pathogenic role in the augmented CB activity and local inflammation via AT₁ receptor activation during IH conditions in patients with sleep‐disordered breathing.