Significant progress has been made in understanding the neurotrophic effects of intermittent fasting (IF), caloric restriction (CR), and exercise in recent decades. These interventions have been shown to improve neuroprotection, synaptic plasticity, and adult neurogenesis (NSPAN) through various signaling pathways and processes. One key aspect of these effects is the metabolic switch from glucose to ketone bodies as cellular fuel. More recently, calorie restriction mimetics (CRMs) such as resveratrol and other polyphenols have also been investigated in relation to NSPAN. This review synthesizes recent findings on the essential functions of IF, CR, and exercise and presents the most important molecules involved. It highlights researched signaling pathways (PI3K, Akt, mTOR, AMPK, GSK3β, ULK, MAPK, PGC-1α,NF-κB,sirtuins ,Notch,Sonic hedgehog,and Wnt) and processes (anti-inflammation ,autophagy ,apoptosis ) that support or hinder neuroprotection,synaptic plasticity,and neurogenesis. The annotated bibliography section provides brief summaries of approximately 30 literature reviews related to the neurotrophic effects of IF ,CRMs ,and exercise. These selected reviews primarily focus on healthier aging and reducing the risk of neurodegenerative diseases such as Alzheimer's disease,Huntington's disease,Parkinson's disease,and depression while improving cognitive function. Some reviews also discuss epigenetic factors. Some specific topics covered in the annotated bibliography include endoplasmic reticulum proteins,Sonic hedgehog,morphogens,Wnt,and PARPs.The reviews highlight various aspects related to exercise-induced regulation of reactive oxygen species(ROS)in the brain,the link between exercise,BDNF,and cognition,and how exercise can act as both a producer of ROS and a cause for oxidative stress based on hormesis hypothesis. Overall,this review and annotated bibliography provide a comprehensive overview of the neurotrophic effects of IF,CR,and exercise. It serves as a valuable resource for researchers and readers interested in understanding the molecular mechanisms underlying these interventions and their potential implications for healthier aging and reducing the risk of neurodegenerative diseases. The cited research articles offer further insights into specific aspects of interest within this field.
Significant progress has been made in understanding how fasting, eating less food, and exercising can help our brain. These things can protect our brain, help it change and grow, and make new brain cells. When we don't eat much food, our body starts using different kinds of fuel called ketone bodies instead of glucose. Some substances like resveratrol and polyphenols have also been studied for their effects on the brain. There are many different pathways and processes involved in these effects, including inflammation control, cell recycling, and cell death. A bibliography section provides summaries of many research papers about these topics."
Definitions
- Neurotrophic effects: The positive changes that happen in the brain when we fast or exercise.
- Intermittent fasting (IF): Not eating for certain periods of time.
- Caloric restriction (CR): Eating less food than usual.
- Exercise: Physical activity that makes our body move.
- Neuroprotection: Protecting the brain from damage or harm.
- Synaptic plasticity: The ability of connections between brain cells to change and adapt.
- Adult neurogenesis: The process of creating new brain cells in adults.
- Metabolic switch: Changing the way our body uses energy from glucose to ketone bodies.
- Calorie restriction mimetics (CRMs): Substances that mimic the effects of eating less food.
- Resveratrol: A substance found in some plants that has health benefits.
- Polyphenols: Natural compounds found in
Introduction
Intermittent fasting (IF), caloric restriction (CR), and exercise have been gaining attention in recent decades for their potential neurotrophic effects. These interventions have been shown to improve neuroprotection, synaptic plasticity, and adult neurogenesis (NSPAN) through various signaling pathways and processes. One key aspect of these effects is the metabolic switch from glucose to ketone bodies as cellular fuel. More recently, calorie restriction mimetics (CRMs) such as resveratrol and other polyphenols have also been investigated in relation to NSPAN.
The purpose of this review is to synthesize recent findings on the essential functions of IF, CR, and exercise and present the most important molecules involved. It will highlight researched signaling pathways (PI3K, Akt, mTOR, AMPK, GSK3β, ULK, MAPK, PGC-1α,NF-κB,sirtuins ,Notch,Sonic hedgehog,and Wnt) and processes (anti-inflammation ,autophagy ,apoptosis ) that support or hinder neuroprotection,synaptic plasticity,and neurogenesis.
Molecular Mechanisms Underlying Neurotrophic Effects
Metabolic Switch from Glucose to Ketone Bodies
One key aspect of the neurotrophic effects of IF,Cr,and exercise is the metabolic switch from glucose to ketone bodies as cellular fuel. This switch has been shown to promote neuronal survival by providing an alternative energy source during periods of low glucose availability.
The researchers also observed increased levels of insulin-like growth factor 1 (IGF-1), which is known to promote neurogenesis and synaptic plasticity.
Signaling Pathways Involved
Several signaling pathways have been identified as key players in the neurotrophic effects of IF, CR, and exercise. These include PI3K, Akt, mTOR, AMPK, GSK3β, ULK, MAPK, PGC-1α,NF-κB,sirtuins ,Notch,Sonic hedgehog,and Wnt.
The PI3K/Akt/mTOR pathway has been shown to regulate protein synthesis and cell growth in response to nutrient availability. Studies have also found that this pathway plays a critical role in promoting neuronal survival and synaptic plasticity.
AMPK is another important signaling pathway involved in the neurotrophic effects of IF,Cr,and exercise. It acts as an energy sensor and helps maintain cellular energy homeostasis by regulating glucose uptake and fatty acid oxidation. Activation of AMPK has been linked to increased BDNF levels and improved cognitive function.
Sirtuins are a family of proteins that play a crucial role in regulating cellular metabolism and stress response. They have been shown to be activated by CRMs such as resveratrol and can promote neuroprotection through various mechanisms including regulation of mitochondrial function.
Wnt signaling has also been implicated in the neurotrophic effects of IF,Cr,and exercise. This pathway plays a crucial role in promoting adult neurogenesis by regulating neural stem cell proliferation and differentiation.
Processes Involved
In addition to these signaling pathways, several processes have also been identified as essential for the neurotrophic effects of IF,Cr,and exercise. These include anti-inflammation ,autophagy ,and apoptosis.
Anti-inflammation refers to the reduction or prevention of inflammation within the brain. Chronic inflammation has been linked to various neurological disorders such as Alzheimer's disease, Parkinson's disease, and depression. Studies have found that IF,Cr,and exercise can reduce inflammation in the brain through various mechanisms including regulation of cytokines and immune cells.
Autophagy is a process by which damaged or dysfunctional cellular components are removed and recycled. It plays a crucial role in maintaining cellular homeostasis and has been linked to neuroprotection. Studies have shown that IF,Cr,and exercise can induce autophagy in the brain, leading to improved cognitive function and reduced risk of neurodegenerative diseases.
Apoptosis refers to programmed cell death, which plays an essential role in regulating cell survival and eliminating damaged or unnecessary cells. Dysregulation of apoptosis has been linked to various neurological disorders. Studies have found that IF,Cr,and exercise can promote neuronal survival by modulating apoptotic pathways.
Annotated Bibliography
The following is a brief summary of approximately 30 literature reviews related to the neurotrophic effects of IF ,CRMs ,and exercise:
12) "Sonic hedgehog morphogens during development,cancer,and repair
In the last decades, important progress has been achieved in the understanding of the neurotrophic effects of intermittent fasting (IF), caloric restriction (CR) and exercise. Improved neuroprotection, synaptic plasticity and adult neurogenesis (NSPAN) are essential examples of these neurotrophic effects. The importance in this respect of the metabolic switch from glucose to ketone bodies as cellular fuel has been highlighted. More recently, calorie restriction mimetics (CRMs; resveratrol and other polyphenols in particular) have been investigated thoroughly in relation to NSPAN. In the narrative review sections of this manuscript, recent findings on these essential functions are synthesized and the most important molecules involved are presented. The most researched signaling pathways (PI3K, Akt, mTOR, AMPK, GSK3$\beta$, ULK, MAPK, PGC-1$\alpha$, NF-$\kappa$B, sirtuins, Notch, Sonic hedgehog and Wnt) and processes (e.g., anti-inflammation, autophagy, apoptosis) that support or thwart neuroprotection, synaptic plasticity and neurogenesis are then briefly presented. This provides an accessible entry point to the literature. In the annotated bibliography section of this contribution, brief summaries are provided of about 30 literature reviews relating to the neurotrophic effects of interest in relation to IF, CR, CRMs and exercise. Most of the selected reviews address these essential functions from the perspective of healthier aging (sometimes discussing epigenetic factors) and the reduction of the risk for neurodegenerative diseases (Alzheimer's disease, Huntington's disease, Parkinson's disease) and depression or the improvement of cognitive function.
