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. 2022 Jul 15;12(7):235.
doi: 10.3390/bs12070235.

Lion's Mane (Hericium erinaceus) Exerts Anxiolytic Effects in the rTg4510 Tau Mouse Model

Mya N Rodriguez  1 , Stephen L P Lippi  1
Affiliations

Lion's Mane (Hericium erinaceus) Exerts Anxiolytic Effects in the rTg4510 Tau Mouse Model

Mya N Rodriguez et al. Behav Sci (Basel). .

Abstract

Alzheimer’s disease (AD) significantly impairs the life of an individual both cognitively and behaviorally. Tau and beta-amyloid (Aβ) proteins are major contributors to the etiology of AD. This study used mice modeling AD through the presence of tau pathology to assess the effects of Hericium erinaceus (H. erinaceus), also known as Lion’s mane, on cognitive and non-cognitive behaviors. Despite neurocognitive and neurobiological effects of H. erinaceus being seen in both healthy and transgenic mice, no research to date has explored its effects on mice with solely tau pathology. In this study, mice were placed on a diet supplemented with H. erinaceus or a standard rodent diet for 4.5 months in order to determine the effect of this medicinal mushroom on behavior. Tau mice given H. erinaceus had significantly shorter latencies to enter the center of the open field (OF) (p < 0.05) and spent significantly more time in the open arms of the elevated zero maze (EZM) (p < 0.001) compared to tau control mice. Mice given H. erinaceus spent significantly more time in the open arms of and made more head dips in the elevated zero maze (EZM) (p < 0.05). While H. erinaceus had anxiolytic effects, no improvements were seen in spatial memory or activities of daily living. These findings provide additional support for the anxiolytic effects of H. erinaceus and point to its potential benefit as a therapeutic for anxiety in AD.

Keywords: Alzheimer’s disease; anxiety; behavior; mice; mushrooms; tau.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Weights over time. (A) Mice on the control diet (no H. erinaceus) weighed significantly more than those given H. erinaceus. (B) Male WT mice given the control diet weighed significantly more than their H. erinaceus counterparts at 64 days and 96 days; only male mice are graphed. (C) Female tau mice on the control diet weighed significantly more at each weighing point than female tau mice given H. erinaceus; only female mice are graphed. (D) Female tau mice weighed significantly more than female WT mice. Female tau mice weighed more than female WT mice at days 64, 96, and 128; only control diet mice are graphed. 0 = baseline; error bars represent mean ± SEM. (* p < 0.05, ** p < 0.01, *** p < 0.001).
Figure 2
Figure 2
Wet food consumption over time. (A) Mice on the control diet (no H. erinaceus) ate more food than those given H. erinaceus. (B) Male control diet mice ate more wet food at day 64 (p < 0.01), 96 (p < 0.001), and 128 (p < 0.01) than male mushroom mice. Tau control mice ate significantly more wet food than tau mushroom mice; only male mice graphed. (C) Female mice ate more than male mice at 64 (p < 0.05) and 96 (p < 0.01) days. Female tau mice ate significantly more than male tau mice, p < 0.001. Tau female mice ate significantly more wet food than WT female mice (p = 0.001). WT male mice ate significantly more wet food than Tau male mice, p = 0.001; only H. erinaceus diet condition graphed. (D) Tau control mice ate more than tau mushroom mice at day 32 (p < 0.05) and 128 (p < 0.01). Female mice ate significantly more than male mice, p < 0.05. Male control mice ate significantly more wet food than male mushroom mice, p < 0.001. Female mushroom mice ate significantly more wet food than male mushroom mice, p < 0.001; only tau mice graphed. Error bars represent mean ± SEM.
Figure 3
Figure 3
Dry food consumption over time. As the experiment progressed, mice ate less dry food, p < 0.01. Male tau mice consumed significantly more dry food than male WT mice (p < 0.05). Error bars represent mean ± SEM.
Figure 4
Figure 4
Open field test measures. (A) Tau control mice had significantly longer latencies to enter the center compared to WT control mice. Tau mice supplemented with H. erinaceus had significantly shorter latencies in entering the center of the OF compared to tau control mice. (B) Male mice defecated more than females. Error bars represent mean ± SEM (* p < 0.05, ** p < 0.01).
Figure 5
Figure 5
Head Dips in the EZM. (A) Female mice made significantly more head dips than male mice. (B) Mice given H. erinaceus made significantly more head dips than control mice. (C) Tau mice made significantly more head dips than WT mice. Error bars represent mean ± SEM (* p < 0.05, ** p = 0.01, *** p < 0.001).
Figure 6
Figure 6
Percent time spent in the open arms of the EZM. Tau mice given H. erinaceus spent significantly more time in the open arms compared to tau control mice and tau mice spent more time in the open arms compared to WT mice. Mice given H. erinaceus spent more time in the open arms compared to control mice. Error bars represent mean ± SEM (* p < 0.05, ** p < 0.01, *** p = 0.001).
Figure 7
Figure 7
Latency to find the platform in the MWM. (A) As the days progressed, mice spent less time finding the platform (p < 0.001). (B) Tau mice had significantly longer latencies to find the platform compared to WT mice (p < 0.001) Error bars represent mean ± SEM.
Figure 8
Figure 8
Percent time spent in the target quadrant of the MWM. (A) As the days progressed, mice spent more time in the target quadrant (p < 0.001). (B) WT mice significantly spent more time in the target quadrant compared to tau mice (p < 0.05). Error bars represent mean ± SEM.
Figure 9
Figure 9
MWM thigmotaxicity by genotype. As the days progressed, tau mice spent significantly more time around the border of the MWM compared to WT mice. Tau mice spent significantly more time along the border on days 2–4 and 5 compared to WT mice. Error bars represent mean ± SEM. (** p < 0.01, *** p < 0.001).
Figure 10
Figure 10
Total distance swam in the MWM. (A) As the days progressed, mice swam less total distance, with male mice specifically traveling shorter distances on days 3 through 5 compared to day 1 (p < 0.001). Female mice did not show significant differences in distances throughout the training days. (B) As the days progressed, tau mice traveled a significantly greater distance than WT mice (p < 0.001). Error bars represent mean ± SEM.
Figure 11
Figure 11
MWM probe trial latency to first cross platform. (A) Tau mice had a significantly longer latency to first reach where the platform would be than WT mice. (B) Female WT mice took significantly less time than female tau mice to first cross where the platform would be and female tau mice had a significantly longer latency to first cross where the platform would be than male tau mice. Error bars represent mean ± SEM (** p < 0.01, *** p ≤ 0.001).
Figure 12
Figure 12
Additional MWM Probe Trial measures. (A) WT mice crossed the target significantly more than tau mice. (B) WT mice spent significantly more time in the target quadrant on the probe day than tau mice. (C) Tau mice spent significantly more time in the border (greater thigmotaxicity) than WT mice. Error bars represent mean ± SEM (* p < 0.05, ** p < 0.01).
Figure 13
Figure 13
Burrowing assay measures. (A) Two-hour burrowing assessment. WT mice burrowed significantly more pea-gravel than tau mice after 2 h. (B) At the overnight measure, female WT mice burrowed significantly more than female tau mice. Male tau mice burrowed significantly more than female tau mice and male WT mice burrowed significantly more than male tau mice. Error bars represent mean ± SEM (* p < 0.05, *** p ≤ 0.001).
Figure 14
Figure 14
Nesting behavior. (A) WT mice built significantly better nests than tau mice. (B) Representative nest by mushroom condition and genotype; numbers represent randomly assigned IDs for raters. Error bars represent mean ± SEM (*** p < 0.001).
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