Exercise and antioxidants: A winning combination for brain health?

Your doctors and stroke hospital will completely fail at creating EXACT exercise protocols and EXACT antioxidant protocols. You're screwed because they will do nothing to help you navigate the best course of action. You are surrounded by incompetent stroke medical 'professionals'.  Guidelines like this are the lazy version of professionalism. This would never be allowed in the business world, firings would be the result.

Exercise and antioxidants: A winning combination for brain health?

MedicalXpress Breaking News-and-Events | May 20, 2019

An international team of researchers representing several institutions in Japan and the United States has published promising findings that may stand to benefit people living with the specter of Alzheimer's and other neurodegenerative diseases, as well as age-related cognitive decline.

Advertisement

In their paper published in PNAS, "Leptin in hippocampus mediates benefits of mild exercise by an antioxidant on neurogenesis and memory," Yook and colleagues present results from a series of experiments—murine and in vitro—that elucidate the role of leptin in cognitive function. Leptin is a hormone that is produced in adipose tissue and in the hippocampus, the part of the brain where memory and spatial learning are processed.
The relationship between exercise and improved cognitive function is well established. Likewise, certain dietary supplements, for example, docasahexaenoic acid (DHA) have also shown promise in improving cognition and in slowing or halting cognitive decline. The effect of both exercise and supplementation with an antioxidant on plasticity and cognitive function within the hippocampus has until now been largely unexplored, however. Previous research has demonstrated that leptin in particular is a promising therapeutic target for neurodegenerative diseases such as Alzheimer's.
Yook and colleagues sought to answer the particular question of whether mild exercise (ME) combined with the antioxidant supplement astaxanthin (AX) might confer benefit in terms of cognitive function and neuronal plasticity; and whether or not the two interventions—AX and ME together—could have a synergistic effect beyond the additive effects of either treatment administered separately. The investigators "hypothesized that ME-enhanced hippocampal neurogenesis and memory might be further improved with dietary AX via mediation by a neurotrophic factor such as h-LEP [hippocampal leptin]." To test their hypothesis, they conducted a series of experiments on mice and in vitro using human brain cell lines.

• See Also: Role of leptin in the association between body adiposity and persistent asthma: A longitudinal study

The first experiment examined the performance of four groups of wild-type mice on standard tests used to evaluate murine memory and spatial learning. The mice comprised the following groups: sedentary with placebo (SE+PL); mild exercise with placebo (ME+PL); sedentary with astaxanthin (SE+AX); and mild exercise with astaxanthin (ME+AX). The SE+PL group performed the worst while the ME+PL and SE+AX groups both performed better. The best performers were the mice in the ME+AX group, a finding that supports the enhanced effects of both interventions on memory and spatial learning. The test data were further reinforced by cell counts of Ki67-positive cells and BrdU/NeuN cells, both measures of adult hippocampal neurogenesis (AHN), that showed "a strong additional effect" at work when AX and ME were combined.
To better understand the role of LEP in the changes observed in the mouse brains, the researchers undertook a DNA microarray and gene expression analysis, looking at up- and down-regulated genes in relation to the various groups of mice, and particularly where the genes overlapped between treatment groups. Their results, especially with regard to the antioxidant ABHD3 gene and the LEP gene, confirm the synergistic effect of AX and ME on spatial memory and AHN.
Importantly, the study authors also found after further analysis that circulating plasma leptin levels remained unchanged among treatment groups, a finding which demonstrates that h-LEP—that is, leptin found in the hippocampus—is the specific target molecule responsible for the improvements demonstrated by combined ME+AX therapy. At the protein level, h-LEP and LEPRa (a leptin receptor), were also correlated with improvements in spatial memory, while the AKT/STAT3 signaling pathways were implicated in these improvements as well.
For the in vitro experiment, the investigators used human neuroblastoma cell lines—cells known to endogenously synthesize leptin—to observe the effect of exposing them directly to varying amounts of AX. They noticed a direct dose-dependent response with regard to expressed leptin, as well as up-regulation in the ABHD3 and LEP genes.
Finally, to establish whether or not leptin is required to achieve the synergistic effect seen with the AX+ME mice, Yook and colleagues repeated their earlier mouse experiment on ob/ob knockout mice, using leptin-deficient animals bred for obesity and diabetes research. They found that leptin deficiency did indeed play a role, as these mice performed poorly relative to the wild-type mice, thus confirming leptin as the crucial component of the AX+ME synergy observed in the prior experiment.
To further confirm the mediative effect of leptin in the brain, the scientists injected the ob/ob mice with leptin over the course of 4 weeks, finding that the synergistic effects of AX and ME were restored in these mice. The researchers also observed increased levels of proteins pIGF1R and pP13K in ME+PL and ME+AX groups, independently of whether or not the mice were wild-type or knockout.
The researchers offer further discussion of several details of their study, for example, commenting that "our results of increased leptin and IGF1R support the possibility that the enhancement of AHN and memory function by ME+AX may be due to the interplay of both leptin and IGF1R expression," and also noting a correlation between memory increase and an increase in levels of the hippocampal receptor LEPRa.

• See Also: Study identifies a hormone that may hinder weight loss

While the results shown here in murine models are certainly promising, what might this mean in a clinical context for humans? For one thing, mild exercise for humans has been characterized in this paper as that which is typical of a yoga or tai chi session, which puts it within reach of many people. Another factor is the ready availability of the relatively inexpensive nutritional supplement astaxanthin.
Ultimately, the authors conclude that "our findings advance the notion that ME combined with a dietary antioxidant such as AX, which induces endogenous h-LEP, may be an effective nonpharmacological strategy for preventing or improving cognitive function and brain health, and for slowing cognitive decline. This strategy may be particularly useful in vulnerable individuals, including the elderly."

To read more, click here.

Modulation of neurogenesis via neurotrophic factors in acupuncture treatments for neurological diseases

Massive amounts of appeal to antiquity  and use of the word may.
 
I don't see how acupuncture can have any effects except placebo or spontaneous recovery since energy meridians have never been proven to exist.
http://www.sciencedirect.com/science/article/pii/S0006295217302460

• Hwa Kyoung Shin^{a, b, c, d},
• Sae-Won Lee^{a, b},
• Byung Tae Choi^{a, b, c, d, ,}

 Show more

https://doi.org/10.1016/j.bcp.2017.04.029

Get rights and content

---

Abstract

Acupuncture is one of the main healing arts in Oriental medicine. It has long been used in East Asian countries, including Korea and China, and is thought to be an effective alternative treatment for various neurological diseases. The therapeutic effects of acupuncture come from inserting a needle at specific acupoints on the body surface, with subsequent delivery of stimulation via manual rotation or electric pulses (electroacupuncture, EA). In various neurological disease models, peripheral nerve stimulation using acupuncture or EA may have protective effects on neural tissues by increasing expression of neurotrophic factors (NTFs), such as brain-derived neurotrophic factor and glial-derived neurotrophic factor, in the central nervous system, especially the brain. In addition, acupuncture may contribute to recovery from functional impairments following brain damage by encouraging neural stem cell proliferation, which is active at the initial stage of injury, and by further facilitating differentiation. Hence, acupuncture may act as a stimulator activating peripheral nerves at specific acupoints and inducing the expression of various NTFs in the brain. Subsequently, NTFs induced by this treatment trigger autocrine or paracrine signaling, which stimulates adult neurogenesis, thereby exerting therapeutic effects on functional impairments in neurological diseases. Acupuncture may offer an alternative treatment that promotes adult neurogenesis through the expression of NTFs in the brain. It may also have synergistic effects when combined with pharmacological interventions, again facilitating neurogenesis. This review examines recent studies concerning the effects of acupuncture and EA on adult neurogenesis associated with NTF expression in neurological diseases, in particular stroke, Alzheimer’s disease, and Parkinson’s disease.

Neuroscientist Shows What Fasting Does To Your Brain & Why Big Pharma Won’t Study It

And I bet your doctor will not be informing you of these benefits or even have a stroke diet protocol for you.
http://www.collective-evolution.com/2015/12/11/neuroscientist-shows-what-fasting-does-to-your-brain-why-big-pharma-wont-study-it/
Mark and his team have published several papers that discuss how fasting twice a week could significantly lower the risk of developing both Parkinson’s and Alzheimer’s disease.

Fasting does good things for the brain, and this is evident by all of the beneficial neurochemical changes that happen in the brain when we fast. It also improves cognitive function, increases neurotrophic factors, increases stress resistance, and reduces inflammation.

Fasting is a challenge to your brain, and your brain responds to that challenge by adapting stress response pathways which help your brain cope with stress and risk for disease. The same changes that occur in the brain during fasting mimic the changes that occur with regular exercise. They both increase the production of protein in the brain (neurotrophic factors), which in turn promotes the growth of neurons, the connection between neurons, and the strength of synapses.

More at link with the TEDx video.

Interplay between nitric oxide and brain-derived neurotrophic factor in neuronal plasticity

So go ask your doctor EXACTLY what you should be doing about getting nitric oxide for your recovery. BDNF is important, does your doctor know anything about its use for recovery? I have 50 posts on nitric oxide  and 78 posts on BDNF if you need to train your doctor on the subjects.
http://europepmc.org/abstract/med/26350341

(PMID:26350341)

• Abstract
• Citations
• BioEntities
• Related Articles
• External Links

Biojone C, Casarotto PC, Joca SR, Castrén E

Neuroscience Center, University of Helsinki, Viikinkaari 4, 00790, Helsinki, Finland. caroline.biojone@helsinki.fi.

CNS & Neurological Disorders Drug Targets [2015]

Type: Journal Article

Abstract

Highlight Terms Gene Ontology(1) Genes/Proteins(5) Species(1) Chemicals(2)

Nitric oxide is a gaseous neuromodulator that displays a core role in several neuronal processes. Beyond regulating the release of neurotransmitters, nitric oxide also plays a role in cell differentiation and maturation in the central nervous system. Although the mode of action of nitric oxide is not fully understood, it involves the activation of soluble guanylate cyclase as well as the nitration and S-nitrosylation of specific amino acid residues in other proteins. Brain-derived neurotrophic factor is a member of neurotrophic factor family and, acting through its receptor tropomyosin-related kinase B, increases the production of nitric oxide, modulates neuronal differentiation and survival, and plays a crucial role in synaptic plasticity, such as long-term potentiation. Furthermore, nitric oxide is an important regulator of the production of these factors. The aim of the present review is to present a condensed view of the evidence related to the interaction between nitric oxide and brain-derived neurotrophic factor. Additionally, we conducted bioinformatics analysis based on the amino acid sequences of brain-derived neurotrophic factor and tropomyosin-related kinase receptors, and proposed that nitric oxide might nitrate/S-nitrosylate these proteins. Thus, we suggest a putative direct mode of action between these molecules to be further explored.

Liraglutide is neurotrophic and neuroprotective in neuronal cultures and mitigates mild traumatic brain injury in mice

Is this enough evidence to create clinical trials in humans? Whom can we ask that question of? There is no one because no one is in charge of stroke. . Because every stroke professional in the world is waiting for SOMEONE ELSE TO SOLVE THE PROBLEM.
Three years ago this was reported;

GLP-1R Agonist Liraglutide Activates Cytoprotective Pathways and Improves Outcomes After Experimental Myocardial Infarction in Mice

yet we are no farther along in this because why?

http://onlinelibrary.wiley.com/doi/10.1111/jnc.13169/abstract 

1. Yazhou Li^1,†,*,
2. Miaad Bader^2,†,
3. Ian Tamargo¹,
4. Vardit Rubovitch²,
5. David Tweedie¹,
6. Chaim G. Pick^2,3,‡ and
7. Nigel H. Greig^1,‡,*

DOI: 10.1111/jnc.13169

This article is protected by copyright. All rights reserved.

Issue

Journal of Neurochemistry

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Get PDF (687K)

Abstract

Traumatic brain injury (TBI), a brain dysfunction for which there is no present effective treatment, is often caused by a concussive impact to the head and affects an estimated 1.7 million Americans annually. Our laboratory previously demonstrated that exendin-4, a long-lasting glucagon-like peptide 1 receptor (GLP-1R) agonist, has neuroprotective effects in cellular and animal models of TBI. Here, we demonstrate neurotrophic and neuroprotective effects of a different GLP-1R agonist, liraglutide, in neuronal cultures and a mouse model of mild TBI (mTBI). Liraglutide promoted dose-dependent proliferation in SH-SY5Y cells and in a GLP-1R over-expressing cell line at reduced concentrations. Pretreatment with liraglutide rescued neuronal cells from oxidative stress- and glutamate excitotoxicity-induced cell death. Liraglutide produced neurotrophic and neuroprotective effects similar to those of exendin-4 in vitro. The cAMP/PKA/pCREB pathway appears to play an important role in this neuroprotective activity of liraglutide. Furthermore, our findings in cell culture were well-translated in a weight-drop mTBI mouse model. Post-treatment with a clinically relevant dose of liraglutide for 7 days in mice ameliorated memory impairments caused by mTBI when evaluated 7 and 30 days post trauma. These data cross-validate former studies of exendin-4 and suggest that liraglutide holds therapeutic potential for the treatment of mTBI.

Enhancement of hippocampal neurogenesis by lithium

This is in rodents so don't start bugging your doctor that you need lithium. Unless maybe you are already taking this for bipolar or Schizophrenia.
http://www.ncbi.nlm.nih.gov/pubmed/10987856 

Chen G¹, Rajkowska G, Du F, Seraji-Bozorgzad N, Manji HK.

Author information

Abstract

Increasing evidence suggests that mood disorders are associated with a reduction in regional CNS volume and neuronal and glial cell atrophy or loss. Lithium, a mainstay in the treatment of mood disorders, has recently been demonstrated to robustly increase the levels of the cytoprotective B-cell lymphoma protein-2 (bcl-2) in areas of rodent brain and in cultured cells. In view of bcl-2's antiapoptotic and neurotrophic effects, the present study was undertaken to determine if lithium affects neurogenesis in the adult rodent hippocampus. Mice were chronically treated with lithium, and 5-bromo-2-deoxyuridine (BrdU) labeling of dividing cells was conducted over 12 days. Immunohistochemical analysis was undertaken 1 day after the last injection, and three-dimensional stereological cell counting revealed that lithium produced a significant 25% increase in the BrdU-labeled cells in the dentate gyrus. Double-labeling immunofluorescence studies were undertaken to co-localize BrdU-positive cells with neuron-specific nuclear protein and showed that approximately 65% of the cells were double-labeled. These results add to the growing body of evidence suggesting that mood stabilizers and antidepressants exert neurotrophic effects and may therefore be of use in the long-term treatment of other neuropsychiatric disorders.

Early Mobilisation Following Stroke

These people still don't understand that therapy after the stroke is not where research should take place. You stop the neuronal cascade of death and that will result in much less death and disability. Once again we see that nothing exists as standardized stroke protocols.  Why do I have to point out these fucking simplistic facts.
http://www.touchneurology.com/articles/early-mobilisation-following-stroke

download pdf view ejournal Order reprints

Stroke is a sudden loss of cerebral blood flow caused either by occlusion (85 % of cases) or rupture of the cerebral artery manifesting with focal neurological deficits.¹ One-third of stroke patients are younger than and two-thirds are older than 65 years of age.² Stroke can have both immediate and ongoing physical consequences. Disability and mortality represent the most relevant clinical outcomes. The degree of disability varies from devastating outcome with total dependence on family/carer to minimal and manageable disability.³ Within 12 months of stroke, one-third of stroke patients will die and another third are left with restriction in performing simple activities of daily living (ADL). Considering the high prevalence of the disease, the burden of post-stroke disability is of primary public health importance, translating to a substantial cost worldwide. In the US in 2008, for example, the direct and indirect costs of stroke are estimated to be more than $65 billion.⁴ Much of this cost probably relates to the physical disability. Any treatment that improves functional outcome can significantly reduce disability and costs, setting regaining of functional independence, defined as improvement in mobility and activities of ADL, as an important goal.⁴ The potential for recovery varies substantially across stroke patients. Factors associated with poor functional recovery include stroke severity, age and, to a lesser extent, diabetes.⁵

Today, rehabilitation is recognised as a cornerstone of multidisciplinary stroke care and can reduce the number of patients who are left handicapped. Forty per cent of stroke patients require active rehabilitation services.³ In recent years, rehabilitation has been shown to influence both brain recovery and reorganisation, especially in relation to motor impairment. Comprehensive rehabilitation programmes appear to improve functional recovery over standard care in terms of speed and extent of recovery.⁶ It is noteworthy that neurological recovery is not linear and most of it occurs within the first 3–6 months, although some patients show recovery over prolonged timelines.

Rehabilitation intensity depends on the status of the patient and degree of disability. If the patient is unconscious, rehabilitation is passive to prevent contractions, pressure ulcers and to prevent distress when movement is regained.³ However, there is still debate regarding the optimal intensity of physical therapy following stroke, with conflicting results across the different studies ranging from no benefit to significant functional improvement.⁶ This discrepancy may reflect differences in methodology, patient selection and outcome scales.


The Rationale Behind Very Early Mobilisation
Very early mobilisation (VEM) is a distinctive characteristic of care that involves starting mobilisation, including sitting up, getting out of bed, standing and walking, early after stroke and continuing at frequent intervals. However, the exact meaning of VEM is not well established and varies between 1 day to 3 months following symptoms onset.⁷

Previous studies have shown that induction of neurotrophic factors is associated with neural repair within the first 2 weeks after stroke and, thus, may modulate greater plasticity that may restore function in the periinfarct tissue and supplementary motor areas.⁸ This experience dependent cortical plasticity has been well documented in normal and injured brains.⁷ It may also enable the brain to better respond to rehabilitation, suggesting that efficacy of therapy may vary considerably with the timeline of initiation. The interaction between plasticity and recovery is, however, complicated and individualistic; therefore, it is of importance to apply the appropriate rehabilitation strategy at the appropriate time. Efforts are being made to develop more efficient rehabilitate strategies that utilise current knowledge of cortical plasticity. In addition to enhancing plasticity, VEM may prevent complications with a high risk of causing harm such as deep vein thrombosis, pulmonary embolism, contractures, infections, sores, muscle atrophy and deterioration in cardiorespiratory function. The complications associated with immobility were shown to be responsible for 51 % of deaths in patients with cerebral infarction.⁹ In another analysis of stroke unit systems,⁹ stroke unit care appeared to reduce complications of immobility, and infections, in particular. Early mobilisation may also have important psychological effects on a patient’s motivation, well-being and quality of life.<sup>6

Another page and references at link.</sup>

Plasticity beyond peri-infarct cortex: Spinal up regulation of structural plasticity, neurotrophins, and inflammatory cytokines during recovery from cortical stroke

I'm sure your wonderful up-to-date doctor can explain all this and how it is already incorporated into your 100% recovery protocol. You don't have a 100% recovery protocol? Why not? Is your doctor incompetent?

Plasticity beyond peri-infarct cortex: Spinal up regulation of structural plasticity, neurotrophins, and inflammatory cytokines during recovery from cortical stroke

• Bernice Sist^{a, d,} ,
• Karim Fouad^{a, b,} ,
• Ian R. Winship^{a, c, d, ,}

• ^a Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada T6G 2R3
• ^b Faculty of Rehabilitative Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2R3
• ^c Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada T6G 2R3
• ^d Neurochemical Research Unit, University of Alberta, Edmonton, Alberta, Canada T6G 2R3

Choose an option to locate/access this article:

Check if you have access through your login credentials or your institution

Check access

Purchase $35.95

• 

---

Highlights

•

Cortical stroke induces heightened expression of GAP-43 in the spinal cord

•

Plasticity in the spinal cord after cortical stroke has a finite temporal window

•

TNF-α, IL-6, and NT-3 protein levels in spinal cord correlate with GAP-43 levels

•

BDNF increases transiently in spinal cord prior to heightened GAP-43 expression

---

Abstract

Stroke induces pathophysiological and adaptive processes in regions proximal and distal to the infarct. Recent studies suggest that plasticity at the level of the spinal cord may contribute to sensorimotor recovery after cortical stroke. Here, we compare the time course of heightened structural plasticity in the spinal cord against the temporal profile of cortical plasticity and spontaneous behavioural recovery. To examine the relation between trophic and inflammatory effectors and spinal structural plasticity, spinal expression of brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured. Growth-associated protein 43 (GAP-43), measured at 3, 7, 14, or 28 days after photothrombotic stroke of the forelimb sensorimotor cortex (FL-SMC) to provide an index of periods of heightened structural plasticity, varied as a function of lesion size and time after stroke in the cortical hemispheres and the spinal cord. Notably, GAP-43 levels in the cervical spinal cord were significantly increased after FL-SMC lesion, but the temporal window of elevated structural plasticity was more finite in spinal cord relative to ipsilesional cortical expression (returning to baseline levels by 28 post-stroke). Peak GAP-43 expression in spinal cord occurred during periods of accelerated spontaneous recovery, as measured on the Montoya Staircase reaching task, and returned to baseline as recovery plateaued. Interestingly, spinal GAP-43 levels were significantly correlated with spinal levels of the inflammatory cytokines TNF-α and IL-6 as well as the neurotrophin NT-3, while a transient increase in BDNF levels preceded elevated GAP-43 expression. These data identify a significant but time-limited window of heightened structural plasticity in the spinal cord following stroke that correlates with spontaneous recovery and the spinal expression of inflammatory cytokines and neurotrophic factors.

Abbreviations

• IC, ipsilesional cortex;
• CC, contralesional cortex;
• CSC, cervical spinal cord;
• LSC, lumbar spinal cord;
• FL-SMC, forelimb sensorimotor cortex;
• GAP-43, growth associated protein-43;
• TNF-α, tumor necrosis factor - alpha;
• IL-6, interleukin 6;
• BDNF, brain derived neurotrophic factor;
• NT-3, neurotrophin-3

Keywords

• Ischemia;
• Sensorimotor cortex;
• Plasticity;
• Spinal cord;
• Inflammation;
• Neurotrophins;
• GAP-43;
• TNF-alpha;
• IL-6;
• BDNF;
• NT-3

Nerve Growth Factor, Brain-Derived Neurotrophic Factor, Neurotrophin-3 and Glial-Derived Neurotrophic Factor Enhance Angiogenesis in a Tissue-Engineered In Vitro Model

We need angiogenesis to support stem cells and migrating neurons to the damaged area. Ask your doctor to apply this to your recovery. Its going to take some intellect to transfer this knowledge from skin to the brain.
http://online.liebertpub.com/doi/abs/10.1089/ten.tea.2012.0745

ABSTRACT

Skin is a major source of secretion of the neurotrophic factors nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and glial-derived neurotrophic factor (GDNF) controlling cutaneous sensory innervation. Beside their neuronal contribution, we hypothesized that neurotrophic factors also modulate the cutaneous microvascular network. First, we showed that NGF, BDNF, NT-3, and GDNF were all expressed in the epidermis, while only NGF and NT-3 were expressed by cultured fibroblasts, and BDNF by human endothelial cells. We demonstrated that these peptides are highly potent angiogenic factors using a human tissue-engineered angiogenesis model. A 40% to 80% increase in the number of capillary-like tubes was observed after the addition of 10 ng/mL of NGF, 0.1 ng/mL of BDNF, 15 ng/mL of NT-3, and 50 ng/mL of GDNF. This is the first characterization of the direct angiogenic effect of NT-3 and GDNF. This angiogenic effect was mediated directly through binding with the neurotrophic factor receptors tropomyosin-receptor kinase A (TrkA), TrkB, GFRα-1 and c-ret that were all expressed by human endothelial cells, while this effect was blocked by addition of the Trk inhibitor K252a. Thus, if NGF, BDNF, NT-3, and GDNF may only moderately regulate the microvascular network in normal skin, they might have the potential to greatly increase angiogenesis in pathological situations.

Energy Intake and Exercise as Determinants of Brain Health and Vulnerability to Injury and Disease

Ask your doctor about dietary energy restriction(fasting) if that will help you get superior cognition.
http://www.sciencedirect.com/science/article/pii/S1550413112004020
Evolution favored individuals with superior cognitive and physical abilities under conditions of limited food sources, and brain function can therefore be optimized by intermittent dietary energy restriction (ER) and exercise. Such energetic challenges engage adaptive cellular stress-response signaling pathways in neurons involving neurotrophic factors, protein chaperones, DNA-repair proteins, autophagy, and mitochondrial biogenesis. By suppressing adaptive cellular stress responses, overeating and a sedentary lifestyle may increase the risk of Alzheimer’s and Parkinson’s diseases, stroke, and depression. Intense concerted efforts of governments, families, schools, and physicians will be required to successfully implement brain-healthy lifestyles that incorporate ER and exercise.