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

SIMPLE SUMMARY: With the increase in the geriatric population worldwide, the promotion of healthy aging arose as a key issue and, hence, the scientific community dedicates huge effort to counteract age-related impairments. Brain aging is a crucial risk factor for several neurodegenerative disorders and dementia. One of the most affected cognitive functions is recognition memory. Inflammation and oxidative stress play a key role in pathogenesis of cognitive impairments, and a link exists between frailty, oxidative stress, and inflammaging. Medicinal mushrooms represent a source to develop new therapeutic strategy, and among them Hericium erinaceus (He) displays several actions ranging from boosting immune system to fighting senescence, due to its active ingredients/metabolites. Among these, Ergothioneine (ERGO) is known as the longevity vitamin. Currently, when monitoring physiological aging in mice, we demonstrated the selective, preventive and neuroprotective effect of an ERGO-rich He primordium extract in hippocampus, preventing recognition memory decline during aging, decreasing key markers of inflammation and oxidative stress, and increasing the expression of glutamate receptors, which are crucially involved in glutamatergic neurotransmission. 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.