Nutrition and Drugs

Lion’s Mane Mushroom Benefits Memory and Cognition

By October 5, 2018 No Comments

As contemporary research trends are beginning to gravitate towards natural medicine treatment options, a medicinal fungus commonly referred to as lion’s mane mushroom (Hericium erinaceus) is gaining a lot of attention for its health benefits and nootropic abilities.

In this article, we will review some experiments which helped establish the effects and benefits that lion’s mane mushroom (also known as Satyr’s beard or Yamabushitake) has on cognition. Relevant animal models and behavioral mazes will be discussed.

Lion’s Mane Mushroom and its Benefits

Lion’s mane mushroom is a medicinal fungus with many health benefits. Several studies have already demonstrated its antibacterial and anticarcinogenic effects.[1]

Currently, research is directed towards exploring how the nootropic lion’s mane can improve behavior and cognition across different animal models.

Lion’s Mane Extract Has Antidepressant-like Effects

Hericium erinaceus can be cultured and a vast array of natural products can be extracted from it. For example, when culturing mycelium (the part of the fungus that is located in the soil and has the function of absorbing nutrients) diterpenoids can be isolated from it (specifically, erinacines) which have been demonstrated to be able to enhance nerve growth factor biosynthesis in astrocytes.[2-4] Erinacine A, a type of diterpenoid found in Hericium erinaceus, has been shown to have neurotrophic activity, enhancing cognition even in the context of Alzheimer’s disease. So, a group of researchers set out to find whether erinacine A-enriched Hericium erinaceus could also have a positive effect on a depression-like state caused by excessive stress.[5]

Stress has been determined to be a major determinant for developing depression since it can prompt neuroinflammation, neuroplastic deficits, and mitochondrial damage.[6-7]  Furthermore, using animal studies, stress and depressive disorders have been found to alter levels of neurotransmitters such as serotonin.[8] To determine the effect of Hericium erinaceus on depression, a restraint stress-induced mouse model of depression was used.

In the experiment, Hericium erinaceus was given to mice daily for the span of 4 weeks at doses 100, 200, or 400 mg/kg body weight. After the first 2 weeks passed, the restraint stress protocol began and lasted for 14 days (for all mice except those serving as controls).[9]

To assess depression, the Tail Suspension Test and the Forced Swim Test were administered, both are industry standards for determining depressive-like behaviors in rodents.

In the Tail Suspension Test, mice are hung upside down by their tails and their behavior is quantified based on how much movement or escape-oriented behaviors is exhibited. Bouts of immobility, where the rodent is not displaying movement, are indicative of depressive-like behavior. In the experiment, the researchers found that the untreated restraint-stressed mice had an average of 100 seconds of immobility time, compared to the normal controls’ average of 40 seconds. The dosage levels of 200 and 400 mg/kg body weight daily for four weeks were associated with a significant decrease in immobility time during the Tail Suspension Test.

In the Forced Swim Test, where mice are placed in a body of water that does not have an exit route and are subjected to swimming, movement is quantified in a similar manner as in the Tail Suspension Test and immobility (where a mouse is barely moving, only enough to hold its head above water to breathe) is still a marker for depressive-like behaviors. The researchers found that the normal controls had a swimming time averaging about 160 seconds while the untreated restraint-stress mice had an average of 100 seconds of swimming time. Swimming time in mice treated with lion’s mane mushroom was significantly higher at all three dosage levels (100, 200, and 400 mg/kg) when compared with the untreated depressed mice, averaging roughly 130, 140, and 150 seconds of swimming time, respectively. When measuring immobility time, the normal controls averaged about 75 seconds while the untreated restraint-stressed mice averaged 150 seconds. Of the mice treated with Hericium erinaceus extract, only the 200 and 400 mg/kg conditions had significantly lower immobility time than the untreated depressed mice.

The same experiment also assessed the mice’s performance in the Elevated-Plus Maze and found that the depressed mice treated with lion’s mane mushroom displayed a significant increase in the number of entries into the open arms of the maze when treated with doses of 200 and 400 mg/kg; a 21.1% and 24.1% increase in entries, respectively. While there were no group differences in the number of closed-arm entries, the mice treated with Hericium erinaceus at doses of 200 and 400 mg/kg also spent more time in the open arms of the maze.

These behavioral improvements clearly demonstrate how lion’s mane mushroom is a nootropic and can improve cognition.

Lion’s Mane Improves Memory in Alzheimer’s Mouse Model

In order to get a closer look at how Hericium erinaceus affects impaired memory, a group of researchers induced an Alzheimer’s Disorder (AD) mouse model through a D-galactose (D-gal) injection combined with AlCl3 intragastric administration. This method for inducing AD creates AD-like symptoms and pathological alterations.

The researchers used female BALB/c mice and housed them in groups of 10. The AD mouse model was established through daily injections of D-gal at 120 mg/kg and AlCl3 intragastrically at 20 mg/kg for the span of 10 weeks. (Also, a control group was administered with saline instead of the AD-inducing compounds.) The Morris Water Maze was used to establish that the AD modeling was effective. Once the mice successfully developed AD, they were divided into experimental and control groups. Lion’s mane mushroom extract was given daily at dosage levels 0.3, 1, and 3 g/kg, depending on assigned condition, for a duration of 4 weeks. An AD control group was made up of mice that developed AD but were treated with saline supplements instead of lion’s mane mushroom extract.[10]

In the Morris Water Maze, the non-treated AD mice’s escape latency time was twice as much as that of the normal mice (requiring an average of 83 seconds to find the hidden platform compared to the controls’ 41 seconds). In the treated AD condition, all three dosage levels of lion’s mane mushroom significantly lowered the escape latency time. A decrease in the time needed to complete the Morris Water Maze and locate the hidden platform indicates that lion’s mane supplementation significantly improved their learning and memory abilities.

The mice modeled with Alzheimer’s disease benefited from the lion’s mane supplement. The nootropic improved the experimental mice’s memory and performance significantly.

Effects of Lion’s Mane Mushroom on amyloid β(25-35) peptide-induced learning and memory deficits in mice

In another experiment, a different mouse model characterized by deficits in learning and memory, was used, in order to assess the extent to which Hericium erinaceus can ameliorate cognitive impairments in male 5-week-old ICR mice.

The mice were on a diet containing Hericium erinaceus for a span of 23 days. On days 7 and 14, the mice received 10 μg of amyloid β(25-35) peptide intracerebroventricularly, in order to induce the learning and memory deficits. The control group had amyloid peptide-induced memory deficits but simply did not receive Hericium erinaceus.[11]

On day 21 of the experiment, mice were subjected to the Y-Maze. Typically, when placed in the maze, the mice are expected to enter one of the maze’s arms which they have not entered before. This choice reflects their spatial memory capacity and is formally known as “spontaneous alternation.” The two measurements typically acquired from using the Y-Maze are the alternation percentage between the arms and the total of arm entries during the testing period. In this experiment, the alternation behavior measured in the control group significantly decreased, but those receiving Hericium erinaceus did not have such a dramatic decrease in their alternation behavior and the improvement verged on significance. In the total number of entries, there was no significant difference among the control amyloid β(25-35) group and the amyloid β(25-35) group receiving Hericium erinaceus supplements.

In the same mice, on days 21-23 of the experiment, memory was further assessed using the Novel Object Recognition Test. This test can determine how well the animals can remember if an object is familiar or novel based on the amount of time that the animal interacts with the object. Typically, mice spend more time with unfamiliar objects due to the novelty effect. If a mouse spends a lot of time with an object that it has encountered previously, it means that the mouse does not have memory traces of the previous encounter and thus falsely treats the object as it is novel. Typical measurements acquired in this task include: the number of approaches the mouse makes towards the object, the total time or duration of the approaches, the average duration of an approach, the latency of the first approach, the total latency between the approach, and the average latency between the approach.

So, in the Novel Object Recognition Test, the untreated mice with the amyloid β(25-35)-induced memory impairments interacted with the familiar object as though it was new, spending equal amounts of time exploring the familiar and novel objects. The researchers interpreted this behavior to signify a deficit, an indication that these mice could not visually discriminate and remember which object they had already interacted with in the past. However, the amyloid β(25-35) mice that received the Hericium erinaceus nootropic supplementation had significantly longer exploration time for the novel object and their discrimination ratio was significantly higher than the amyloid β(25-35) mice’s.

Lion’s Mane Enhances Recognition Memory in Wild-Type Mice

In addition to researching how Lion’s mane mushroom affects cognition in impaired mice, establishing how this medicine mushroom impacts healthy, normal organism is an important area of research.

In order to do just that, a group of researchers set out to investigate how Hericium erinaceus affects memory in wild-type mice; strain C57BL-6J (mice which are commonly used to serve as controls during experiments). Only male mice were used in this experiment, in order to avoid potential differences in behaviors due to the estrous cycle that females have. The male C57BL-6J mice were divided into two conditions: the control group received dextrin supplementation (a sugar pill with no significant effects on behavior serving as placebo) and the treated group received 0.025 g/g of Hericium erinaceus. Supplementation in both groups lasted for the span of 2 months.[12]

To determine any behavioral differences in novelty exploration of a new environment, the Emergence Test was used. The Emergence Test is a variant of the Open-Field Test but contains a small opaque cylinder in the center, so that mice have a safe enclosure available to them within the open field, and assesses the exploratory behavior of a novel environment. Prior to the test, mice are acclimated to the small opaque cylinder by being housed in a compartment. The primary measurement of anxiety-like behavior and exploration is measured by the latency that it takes for the mouse to emerge into the novel arena. Auxiliary markers include the amount of time the mice spent in the open area and the number of times they emerge from the closed cylinder.

Between the C57BL-6J mice that were given dextrin supplementation for 2 months and those given Hericium erinaceus, the latter group was much more explorative and, thus, had lower levels of anxiety. The wild-type mice on Hericium erinaceus exhibited a higher frequency of exits from the compartment (2.3-fold higher than the controls), spent more time out in the open exploring the new environment (2.2 times longer), and had a lower latency for the first exit (2.4 times shorter). These measurements indicate that the mice that received Hericium erinaceus for 2 months had a large increase in novelty-seeking behavior.

Also, the Novel Object Recognition Test was employed, in order to measure the mice’s exploratory behavior with a novel object and to determine visual recognition memory abilities.

Compared to the control mice receiving dextrin, the mice receiving Lion’s mane had a much shorter latency for the first approach with the novel object. This means that it took the Hericium erinaceus-treated mice significantly less time to approach the novel object than it did for the control group. Furthermore, behavioral analysis between the two groups revealed that the Hericium erinaceus-treated mice showed a 36% increase in the number of approaches and a 44% increase in the total duration of approaches. Such behavioral findings reveal that Lion’s mane mushroom increases exploratory behavior and enhances recognition memory in mice.  

Lion’s Mane Improves Motor Skills in Parkinson’s Mouse Model

Current research trends are pointing towards a possible effect of lion’s mane mushrooms on the symptoms of Parkinson’s disease. Since Hericium erinaceus has been shown to have beneficial and neuroprotective properties in healthy and diseased animal models, a group of researchers reasoned that it would also have a nootropic effect in the Parkinson’s disease model.

To test this, the researchers utilized the mouse model MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) of Parkinson’s disease, a model which creates Parkinsonian-like motor disturbances in the mouse. The model was first induced via MPTP injections (daily for the span of 5 days) into the dopaminergic nigrostriatal neurons of C57BL/6 mice which were housed individually.[13]

Prior to inducing the animals with Parkinson’s, the mice received pre-treatment, based on the group they were assigned to. Pre-treatment began 25 days prior to the disease model induction. The groups were a sham-operated control with no disease, an MPTP group which received no treatment, three Hericium erinaceus groups with different dosage levels (5.38, 10.76 and 21.52 mg/kg).

Since Parkinson’s is a disorder that is associated with major motor deficits, the Rotarod was a key tool for assessing behavioral abilities. In the Rotarod, mice are placed on the rotating rod and they are challenged to stay on the rotating Rotarod without falling off. The longer the mice stays balanced on the rod, the better.

This experiment established, that all three-dosage levels of Lion’s mane were able to decrease the motor deficits associated with the untreated MPTP condition in a dose-dependent manner.

Lion’s Mane Mushroom and Translational Research

Currently, lion’s mane mushroom is going through clinical trials, in order to assess its impact and effectiveness in human participants with cognitive impairments, depression, and other conditions.

Reduction of Depression and Anxiety in Menopausal Women

One group of researchers explored the effects of lion’s mane on menopausal women. The participants were randomly divided into two groups, the Hericium erinaceus group and the placebo and they received either cookies with Hericium erinaceus (0.5 g of the mushroom’s powdered fruiting body) or placebo cookies for 4 weeks. The participants were told to eat 4 cookies per day and at any point during the day. [14]

The surveys used to assess behaviors were the Center for Epidemiologic Studies Depression Scale (CES-D) and the Indefinite Complaints Index (ICI). The data showed that the mean scores were significantly lower than before on a variety of subscales in the experimental group when compared with the control. Therefore, lion’s mane can possibly decrease anxiety and depression in humans, a further demonstration of its nootropic capabilities

A Double-Blind Clinical Trial for Mild Cognitive Impairment

Gradually, more clinical trials are being conducted, in order to assess how lion’s mane can positively impact humans that have a mild cognitive impairment, the condition that is known to precede Alzheimer’s disease.

In a double-blind placebo-controlled clinical trial testing how Hericium erinaceus affects mild cognitive impairment, subjects were either given a placebo or four 250 mg tablets containing 96% of lion’s mane dry powder which they had to take three times a day for the span of 16 weeks.

Compared to the placebo group, the group that had Hericium erinaceus supplements had increased cognitive function as measured by the Revised Hasegawa Dementia Scale (HDS-R).[15]

This trial also demonstrates the positive effect that lion’s mane can have on cognition, thus should warrant future attention by researchers.

Conclusion

More research using animal models should be conducted in order to discover future applications and uses for Lion’s mane.

Possible directions include the effects of lion’s mane on Parkinson’s and Alzheimer’s disease. Also, research has established that the lion’s mane mushroom has neuroprotective effects in mice subjected to middle cerebral artery occlusion, but the behavioral outcomes have yet to be noted.[16]

Hericium erinaceus appears to be a promising avenue for research and treatment. Future directions should definitely continue studying and exploring the ways that lion’s mane can benefit cognition, behavior, and health. Current findings have already established its potency and efficacy in cognitive-related domains such as memory and mood.

References

  1. Friedman, Mendel. “Chemistry, nutrition, and health-promoting properties of Hericium erinaceus (lion’s mane) mushroom fruiting bodies and mycelia and their bioactive compounds.” Journal of agricultural and food chemistry 63.32 (2015): 7108-7123.
  2. Shimbo, Mari, Hirokazu Kawagishi, and Hidehiko Yokogoshi. “Erinacine A increases catecholamine and nerve growth factor content in the central nervous system of rats.” Nutrition research 25.6 (2005): 617-623.
  3. Mori, Koichiro, et al. “Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human astrocytoma cells.” Biological and Pharmaceutical Bulletin 31.9 (2008): 1727-1732.
  4. Ma, Bing-Ji, et al. “Hericenones and erinacines: stimulators of nerve growth factor (NGF) biosynthesis in Hericium erinaceus.” Mycology 1.2 (2010): 92-98.
  5. Chiu, Chun-Hung, et al. “Erinacine A-enriched Hericium erinaceus mycelium produces antidepressant-like effects through modulating BDNF/PI3K/Akt/GSK-3β signaling in mice.” International journal of molecular sciences 19.2 (2018): 341.
  6. Pittenger, Christopher, and Ronald S. Duman. “Stress, depression, and neuroplasticity: a convergence of mechanisms.” Neuropsychopharmacology 33.1 (2008): 88.
  7. Ulrich-Lai, Yvonne M., and James P. Herman. “Neural regulation of endocrine and autonomic stress responses.” Nature Reviews Neuroscience 10.6 (2009): 397.
  8. Keeney, A., et al. “Differential effects of acute and chronic social defeat stress on hypothalamic‐pituitary‐adrenal axis function and hippocampal serotonin release in mice.” Journal of neuroendocrinology 18.5 (2006): 330-338.
  9. Chiu, Chun-Hung, et al. “Erinacine A-enriched Hericium erinaceus mycelium produces antidepressant-like effects through modulating BDNF/PI3K/Akt/GSK-3β signaling in mice.” International journal of molecular sciences 19.2 (2018): 341.
  10. Zhang, Junrong, et al. “The neuroprotective properties of Hericium erinaceus in glutamate-damaged differentiated PC12 cells and an Alzheimer’s disease mouse model.” International journal of molecular sciences 17.11 (2016): 1810.
  11. Mori, Koichiro, et al. “Effects of Hericium erinaceus on amyloid β (25-35) peptide-induced learning and memory deficits in mice.” Biomedical Research 32.1 (2011): 67-72.
  12. Brandalise, Federico, et al. “Dietary supplementation of Hericium erinaceus increases mossy fiber-CA3 hippocampal neurotransmission and recognition memory in wild-type mice.” Evidence-Based Complementary and Alternative Medicine2017 (2017).
  13. Kuo, Hsing-Chun, et al. “Hericium erinaceus mycelium and its isolated erinacine A protection from MPTP-induced neurotoxicity through the ER stress, triggering an apoptosis cascade.” Journal of translational medicine 14.1 (2016): 78.
  14. Nagano, Mayumi, et al. “Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake.” Biomedical Research31.4 (2010): 231-237.
  15. Mori, Koichiro, et al. “Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double‐blind placebo‐controlled clinical trial.” Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives 23.3 (2009): 367-372.
  16. Hazekawa, Mai, et al. “Neuroprotective effect of repeated treatment with Hericium erinaceum in mice subjected to middle cerebral artery occlusion.” Journal of Health Science56.3 (2010): 296-303.

About Ana Zdravic

Ana Zdravic earned her BSc in Psychology from the University of Houston while minoring in creative writing. She is currently in Europe pursuing her master's degree in cognitive science and is thinking about going for a doctorate. Her research interests include stress, nutrition, exercise, creativity, and quality of life.