Cognitive Healthy Aging in Mice: Boosting Memory by an Ergothioneine-Rich Hericium erinaceus Primordium Extract

Abstract

Brain aging is a crucial risk factor for several neurodegenerative disorders and dementia. The most affected cognitive function is memory, worsening early during aging. Inflammation and oxidative stress are known to have a role in pathogenesis of cognitive impairments, and a link exists between aging/frailty and immunosenescence/inflammaging. Based on anti-aging properties, medicinal mushrooms represent a source to develop medicines and functional foods. In particular, Hericium erinaceus (He) displays several actions ranging from boosting the immune system to fighting senescence, due to its active ingredients/metabolites. Among these, Ergothioneine (ERGO) is known as the longevity vitamin. Currently, we demonstrated the efficacy of an ERGO-rich He primordium extract (He2) in preventing cognitive decline in a murine model of aging. We focused on recognition memory deterioration during aging, monitored through spontaneous behavioral tests assessing both memory components and frailty index. A parallel significant decrease in key markers of inflammation and oxidative stress, i.e., IL6, TGFβ1, GFAP, Nrf2, SOD1, COX2, NOS2, was revealed in the hippocampus by immunohistochemistry, accompanied by an enhancement of NMDAR1and mGluR2, crucially involved in glutamatergic neurotransmission. In summary, we disclosed a selective, preventive and neuroprotective effect of He2 on aged hippocampus, both on recognition memory as well on inflammation/oxidative stress/glutamate receptors expression.

Sex‐specific behavioural, metabolic, and immunohistochemical changes after repeated administration of the synthetic cannabinoid AKB48 in mice

“…Sections 8‐microns thick of both cerebellar vermis and brain hemispheres were cut in the sagittal and coronal plane, respectively, and collected on silane‐coated slides. Hence, because the CNS has more complex specialized structures compared with other tissues, a general staining method, that is, haematoxylin & eosin (H&E), was used to achieve an overview of tissue structures and anatomical order and area‐specific setting (De Luca et al, 2023; Jordan et al, 2011; Li et al, 2022; Roda et al, 2019, 2023; Xiong & Gendelman, 2014). Therefore, using the brightfield examination of H&E‐stained samples at low magnification, and based on the specific target area to be evaluated, neuroanatomical site identification was achieved, allowing the selection of precise sections of cerebellum and dorsolateral prefrontal cortex (DLPFC), which were further processed for histology and immunocytochemical analysis to gauge expected neurotoxicity (Houle, 2011).…”

“…Immunohistochemical labelling extent was evaluated on acquired digitized section images under exposure time avoiding any pixel saturation effect. The labelling intensity was measured utilizing densitometric analysis (Image‐J 1.48i; NIH, Bethesda, MA, USA), as previously reported (Cizkova et al, 2021; De Luca et al, 2023; Roda et al, 2021, 2023). First, the colour of images was inverted to obtain a positive signal lighter on a dark background (instead of the immunoperoxidase staining results), thus correlating the intensifying of immunopositivity with the increasing optical density (OD) values calculated by the software (expressed as mean of light intensity).…”

“…Sections 8-microns thick of both cerebellar vermis and brain hemispheres were cut in the sagittal and coronal plane, respectively, and collected on silane-coated slides. Hence, because the CNS has more complex specialized structures compared with other tissues, a general staining method, that is, haematoxylin & eosin (H&E), was used to achieve an overview of tissue structures and anatomical order and area-specific setting (De Luca et al, 2023;Jordan et al, 2011;Li et al, 2022;Roda et al, 2019Roda et al, , 2023Xiong & Gendelman, 2014).…”

Mitochondrial dysfunction following repeated administration of alprazolam causes attenuation of hippocampus-dependent memory consolidation in mice

“…The paraffin slices of the hippocampal brain were blocked with 3% bovine serum albumin (BSA) at 37° C for 30 min and then incubated overnight with 1% brain-derived neurotrophic factor (BDNF) antibody (ab108319, Abcam) at 4° C. The standard protocols were followed as described previously [ 77 ]. The different regions of the hippocampus were selected to acquire images under a 400× field of view (Eclipse E100, Nikon, Japan).…”

Biologically active secondary metabolites from white-rot fungi

“…The ergothioneine-rich extract exhibited neuroprotective and preventive actions, mitigating age-dependent deficiencies ( Roda et al, 2022 ). Moreover, same extract was shown to reduce oxidative stress and inflammation in the hippocampus, prevent recognition memory decline, and increase the expression of specific receptors crucially involved in glutamatergic neurotransmission in the same mice ( Roda et al, 2023 ).…”