Targeting Neurogenesis with Mushroom Nutrition: A Mini Review - Clinical Journal of Mycology, Jan 2022
Neurogenesis is the process by which new neurons are formed in the brain. Neurogenesis is crucial when an embryo is developing, but also continues in certain brain regions after birth and throughout lifespan. The mature brain has many specialised areas of function, and neurons that differ in structure and connections. The hippocampus, for example, which is a brain region that plays an important role in memory and spatial navigation, alone has at least 122 different types of neurons.
Adult neurogenesis in the dentate gyrus of the hippocampus is highly regulated by several external conditions and cell-intrinsic factors to adapt to environmental changes.
Accumulating evidence suggests that adult-born neurons may play distinct physiological roles in hippocampus-dependent functions, such as memory encoding and mood regulation.
Adult hippocampal neurogenesis is a process that describes the generation of new functional dentate granule cells (DGCs) from adult neural stem cells through the amplification of intermediate progenitors and neuroblasts, as well as the differentiation and integration of these new neurons into the existing neural circuits.
These cells can then project their axons to the Cornu Ammonis 3 (CA3), further establishing the hippocampal circuitry; hence maintaining or improving dendritic complexity is key to hippocampal function, a brain region important for spatial information, learning and memory functions.
When there is a malfunction in any of the processes, then a subsequent breakdown can be expected in either the quiescent pool (stem cell generator), loss of dendritic complexity, angiogenesis or neuroplasticity leading to a loss of memory.
Importance to Maintain Healthy Hippocampal Neurogenesis
Brain cognitive reserve reflects the brains capacity to preserve normal functions, and has been used to explain the gap between tissue damage and clinical symptoms that has been observed in dementia and Alzheimer´s disease (AD)8 . In early/moderate stages of Alzheimer´s disease, cognitive reserve compensates neurodegeneration and allows the maintenance of patients’ cognitive performance.
Table I - The impact of the aforementioned factors can translate into physical changes in brain morphology as outlined in Table II.
Beneficial Factors Deleterious Factors
Cognitive Exercises i.e. crossword, puzzles Sedative Mental Activity i.e. excessive television viewing
Education levels Illiteracy
Creative activities Inadequate diet
Regular Physical Exercise Little Physical Exercise
Social stimulus i.e. Bridge club
Table II - Physical changes in brain morphology
Improvement of cognitive reserve Decline of cognitive reserve
Increased brain size Reduction in brain size
Increase in the number of neurons Reduction in the number of neurons
Increased synaptic density Reduction in synaptic density
Neurogenesis decreases with aging and declines may be linked to compromised cognitive-emotional resilience. Older individuals have less angiogenesis and neuroplasticity and a smaller quiescent progenitor pool.
In these AD patients there is a malfunction of the growth stages of hippocampal neurons or an unexplained severe deletion of these neurons or inability of these neurons to establish an integration within the existing circuitry of hippocampal function.
Due to the aforementioned malfunction and unexplained deletion of these neurons the continued pharmaceutical focus on the reduction of Tau and β-Amyloid proteins may be in need of review. Attempts to treat Alzheimer´s disease with a “reduction” approach to Tau and β-Amyloid proteins has been disappointing . Until a pharmaceutical solution can be proven, could mushroom nutrition act as a disease modifying therapy by nutritionally targeting neurogenesis? How?
By focusing on:
1. Reduction of neuroinflammation by increasing Lipoxin A4. Lipoxin A4 (LXA4) is an endogenously produced eicosanoid that inhibits neutrophil recruitment and activation and blocks the generation of pro-inflammatory proteins. LXA4 acts as an endogenous “breaking signal” in the inflammatory process. Biomass forms of Coriolus versicolor and Hericium erinaceus increased Lipoxin A4 and Aβ uptake by phagocytic cells in rats which is recognized as a potential therapeutic target for AD treatment.
2. Combating viral infections that could be responsible for triggering dementia
Mushroom nutrition can be a source of natural bioactive compounds responsible for prevention and treatment of viral diseases through improvement of human immunomodulation. They boost antiviral cytokines or prevent the entry of the virus into the human cell that are responsible for triggering neurodegeneration.
3. Rebalancing the microbiota in dementia diagnosed patients
Food needs to cover the requirements of the human body and of the microbiota and ensure homeostasis. Mushrooms supply numerous enzymes, nucleosides, nucleotides and secondary metabolites essential for microbiota contributing to cell cycle regulation, apoptosis, autophagy, angiogenesis, metastasis, and signal transduction cascades.
4. Reducing oxidative and cellular stress response
Mushroom nutrition reduces oxidative stress and free radicalinduced cell damage in neurodegenerative conditions.
5. Maintaining hippocampal neurogenesis by supporting Wnt/βcatenin signalling?
The Wnt/β-catenin signalling pathway involves secreted glycoproteins acting through transduction pathways signalling cascade and ligands, controlling carcinogenesis, embryonic development, and tissue regeneration. They are dual function proteins, involved in regulation and coordination of cell–cell adhesion and gene transcription, playing an important role in neurogenesis by enhancing the maturation of the newly generated dendritic network. In fact, β-catenin is a protein with numerous functions in different cellular locations and its regulation is dependent of the action of several interplayers. An important regulator of β-catenin is the glycogen synthase kinase-3β (GSK3β) that promotes β-catenin degradation through its phosphorylation. In pathological conditions in which GSK3β is highly activated, β-catenin is degraded, impairing the cellular processes dependent on its normal function. This degration is evident in AD where both Wnt/β-catenin signalling pathway and β-catenin levels were shown to be decreased in the brain of AD patients . Thus, β-catenin is a powerful therapeutic target, as its overexpression may function as a promoter of maturation and functional integration of immature neurons into the hippocampus. This possible therapeutic intervention may thus counterbalance scenarios where β-catenin is abnormally degraded and dysfunctional.
The researchers demonstrated that supplementation with Coriolus versicolor biomass in mice promotes:
a) Increased dendritic arborization and complexity of newly generated neurons (short and long); and
b) Increase in the levels of β-catenin in the nucleus and cytoplasm of hippocampal newly generated neurons.
This indicates that Coriolus versicolor biomass promotes hippocampal neurogenic reserve in mice by increasing levels of β-catenin that may translate into enhanced cognitive reserve essential for learning and memory (24).
Further clinical research is required to reconfirm these results. The Coriolus versicolor biomass used in this study was supplied by Mycology Research Laboratories Ltd. (Luton, UK). (www.mycologyresearch.com).
Dr. Elisabete Ferreiro CNC-Center for Neuroscience and Cell Biology, CIBB-Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal.. email@example.com Prof.
Tito Fernandes CIISA, Faculty of Veterinary Medicine, Lisbon University, Portugal. firstname.lastname@example.org
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