Professor Frederic Meunier from the Queensland Brain Institute said the team had identified new active compounds from the mushroom, Hericium erinaceus.
“Extracts from these so-called ‘lion’s mane’ mushrooms have been used in traditional medicine in Asian countries for centuries, but we wanted to scientifically determine their potential effect on brain cells,” Professor Meunier said.
“Pre-clinical testing found the lion’s mane mushroom had a significant impact on the growth of brain cells and improving memory.
“Laboratory tests measured the neurotrophic effects of compounds isolated from Hericium erinaceus on cultured brain cells, and surprisingly we found that the active compounds promote neuron projections, extending and connecting to other neurons.
“Using super-resolution microscopy, we found the mushroom extract and its active components largely increase the size of growth cones, which are particularly important for brain cells to sense their environment and establish new connections with other neurons in the brain.”
The study :
Neurotrophins are a family of molecules that promote neuronal survival, neurite outgrowth, and dendritic branching through binding specificity for particular tropomyosin receptor kinase (Trk) and p75 neurotrophin receptors (Kaplan & Miller, 2000). The mammalian neurotrophin family is comprised of nerve growth factor (NGF), brain-derived neurotrophic factor (Ip et al., 1993) (BDNF), neurotrophin 3 (NT3) and neurotrophin 4/5 (NT4/5) (Chao, 2003; Ip et al., 1993).
Both NGF and BDNF neurotrophins also bind to p75 receptor which when expressed together with Trk receptors can promote its high affinity ligand interactions and enhanced trophic signaling resulting in neuronal survival, neurite outgrowth and synaptogenesis (Kaplan & Miller, 2000).
BDNF in particular, is highly expressed in the adult central nervous system (CNS) and is critically important for the function of neurons located in areas of the brain involved in memory acquisition such as the hippocampus and the cortex (Allen et al., 2011). BDNF and its receptor TrkB are essential for long-term potentiation, an Hebbian mechanism strengthening synaptic output in response to a high frequency train of stimulation, as well as learning (Allen et al., 2011; Minichiello et al., 1999).
Dysfunction of the BDNF pathway has been linked with several disorders of the brain, including Alzheimer’s disease (Allen et al., 2011), schizophrenia (Xiu et al., 2009), Huntington’s disease (Zuccato & Cattaneo, 2009), and Rett syndrome (Zuccato & Cattaneo, 2009). Not surprisingly, neurotrophins and their receptors have been identified as targets for the therapeutic treatment of a range of neurodegenerative and neurological disorders (Nagahara & Tuszynski, 2011).
Alternative interventions that increase endogenous BDNF levels or enhance TrkB activity through lifestyle and/or botanical supplements, are also an area of great interest. Ongoing efforts are made to identify compounds derived from natural sources. Traditional Chinese medicine provides an enticing source of potential botanical remedies, with several common drugs stemming from the Chinese pharmacopeia having been used for millennia throughout Asia and India because of their therapeutic or poisonous pharmacologic profiles.
A promising nootropic fungus, known for its neurotrophic profile, comes from Hericium erinaceus, also known as Lion’s Mane mushroom, which, paradoxically, was used to treat unrelated ailments such as stomach aches and as prophylactic treatment of cancers (Kim et al., 2013).
Several studies have reported strong neurotrophic effects, along with the identification of numerous bioactive components, including polysaccharides, erinacines, hericerins, alkaloids, steroids and many others (Brandalise et al., 2017; Friedman, 2015). Interestingly, hericenones and erinacines can effectively cross the BBB (Hu et al., 2019) and exhibit neuroprotective effects both in vitro and to in vivo in animal models of peripheral nerve injury (Wong et al., 2012), and in conditions of the brain including stroke (Hazekawa et al., 2010) and Alzheimer’s disease (Friedman, 2015; Kawagishi & Zhuang, 2008; Mori et al., 2011).
Compounds derived from H. erinaceus extracts have been shown to promote NGF synthesis and secretion (Kawagishi et al., 1996; Lai et al., 2013; Mori et al., 2009; Raman et al., 2015; Zhang et al., 2015) and to act via the TrkA pathway involving MEK/ERK and PI3K/Akt activation (Haure-Mirande et al., 2017; Phan et al., 2014).
However, the NGF/TrkA-mediated neuroprotective effects predominantly focus on neurons in the peripheral nervous system (Ustun & Ayhan, 2019). More recently, H. erinaceus extract has been suggested to also affect the BDNF pathway in 1321 N1 human astrocytoma cell line (Rupcic et al., 2018), in the mouse brain (Chiu et al., 2018) and to promote increasing circulating pro-BDNF levels in humans (Vigna et al., 2019). It is therefore possible that H. erinaceus extract can affect TrkB-dependent central neuronal function.
To test this idea, we purified and identified several compounds and tested their ability to influence TrkB signaling and neuronal morphology in hippocampal neurons. Treatment with H. erinaceus extracts increased neurite outgrowth and branching, and super-resolution structured illumination microscopy revealed much enlarged growth cone morphology.
This neurotropic effect was partially blocked by the TrkB inhibitor ANA-12. We further found that dietary supplementation with H. erinaceus crude extract significantly enhanced recognition memory. Importantly, supplementation with 20–50 times lower concentration of purified hericene A was equally potent at enhancing recognition memory.
Tested rodents exhibited elevated BDNF and TrkB downstream activation effectors levels. However, NDPIH activated ERK1/2 signaling in the absence of TrkB expression in HEK-293 T cells, an effect that was not inhibited by ANA-12. We concluded that hericene A acts via an unknown complementary pathway to increase ERK1/2 signaling. Overall, our results demonstrate that hericene A is a potent memory enhancer that act via a novel signaling pathway converging on ERK1/2 signaling pathway.
reference link: https://onlinelibrary.wiley.com/doi/10.1111/jnc.15767
