- Increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life
- The Science Behind How New Brain Cells Are Generated
- 19 Factors that May Increase Neurogenesis Naturally | Nature Knows
- The Magic of Neurogenesis: How to Help Your Body Make New Brain Cells
Increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life
- Adult neurogenesis
- Cognitive ageing
- Neural stem cells
- An Author Correction to this article was published on 25 February 2020
Functional plasticity of the brain decreases during ageing causing marked deficits in contextual learning, allocentric navigation and episodic memory. Adult neurogenesis is a prime example of hippocampal plasticity promoting the contextualisation of information and dramatically decreases during ageing. We found that a genetically-driven expansion of neural stem cells by overexpression of the cell cycle regulators Cdk4/cyclinD1 compensated the age-related decline in neurogenesis. This triggered an overall inhibitory effect on the trisynaptic hippocampal circuit resulting in a changed profile of CA1 sharp-wave ripples known to underlie memory consolidation. Most importantly, increased neurogenesis rescued the age-related switch from hippocampal to striatal learning strategies by rescuing allocentric navigation and contextual memory. Our study demonstrates that critical aspects of hippocampal function can be reversed in old age, or compensated throughout life, by exploiting the brain’s endogenous reserve of neural stem cells.
Contextual learning, spatial navigation and episodic memory are complex cognitive processes involving hippocampal function1,2,3 and, to some extent, adult neurogenesis4,5,6,7.
Ageing severely affects these, and other, cognitive functions8,9,10,11 and the identification of the causes underlying these deficits and approaches to rescue them has become crucial to address the challenges of a rapidly growing ageing population.
Although it has been postulated that neural reserves can be built up throughout life, or exploited in old age, to compensate for age- or disease-related cognitive impairments12, the true nature and potential of such reserves remain elusive.
Navigation provides a particularly clear example of age-related hippocampal impairment subject of many studies.
In this context, navigational learning strategies switch during ageing from contextual (allocentric, hippocampal dependent) that rely on the cognitive representation of a map of the environment to procedural (egocentric, striatal dependent) that are stereotypical responses independent from spatial cues10,13.
While both strategies can be equally effective if the target and subject positions are constant, only the former provides the flexible update of information that is essential when the target or subject change their relative locations.
Occurring from rodents to humans14,15, this age-dependent loss in contextual navigation has been proposed to depend on several neurophysiological impairments causing, among others, a loss of afferent inputs and changes in the excitation/inhibition balance of the hippocampal circuits leading to alterations in the formation and consolidation of spatial memory representations and imbalances with the striatal, procedural memory system8,9,10,11.
Adult neurogenesis is a hallmark of the hippocampus and dramatically decreases with ageing16,17.
The role of newborn neurons in the dentate gyrus (DG) is unclear but they are thought to act as novel encoding units and/or promote the sparsity of neuronal activity through feed-back inhibition onto granule cells, thus, decreasing the interference among partially overlapping contextual information18,19,20,21.
Consistently, increasing neurogenesis in old mice improved behavioural performance and mnemonic discrimination during contextual learning22,23.
However, un behavioural performance that only considers the subject’s efficacy in addressing a cognitive demand, effects of neurogenesis on the choice of learning strategies were never explored in ageing.
This is important because an assessment of learning strategies, rather than their final efficiency, becomes crucial when trying to understand how the brain processes information resulting in the engagement of different memory systems. In addition, little is known on how newborn neurons contribute in refining the activity patterns beyond the DG towards downstream hippocampal areas. Whether or not an increase in neurogenesis alone is sufficient to rescue the age-dependent switch from hippocampal to striatal learning strategies and navigation was never investigated.
Therefore, given the suggested potential of adult neurogenesis to be exploited as a resource to compensate for age- or disease-related cognitive losses4,24, we here investigated during ageing the use of a system to genetically increase neurogenesis that was originally developed by our group in young mice25. Specifically, this system was the overexpression of Cdk4/cyclinD1 (4D for brevity) in neural stem and progenitor cells (NSC) to increase both their cell cycle activity and numbers through symmetric proliferative divisions26,27. This was shown to trigger the expansion specifically of long-term, symmetrically dividing, radial neural stem cells leading to an increase in the number of newborn neurons generated during embryonic development28,29 and in both adult neurogenic niches of young mice25,30.
We found that 4D was effective in compensating the physiological, age-dependent decrease in neurogenesis both acutely in old mice as well as chronically throughout life.
This cell-intrinsic, genetically-driven expansion of NSC in the DG correlated with an overall inhibition of hippocampal activity that might be important in counteracting the excitation/inhibition imbalance of its downstream circuit arising during ageing.
Most importantly, increased neurogenesis rescued the use of more effective contextual learning strategies and allocentric navigation, hence, rejuvenating critical aspects of brain function.
To investigate the potential of adult neurogenesis to rejuvenate hippocampal function, we explored the use of a system established by our group in the young hippocampus and 4D overexpression by stereotaxic injection of HIV-based, lentiviral vectors25 (Fig. 1a). Since NSC are depleted and/or lose their neurogenic potential during ageing31,32, it was first essential to assess whether 4D would still be effective in rescuing neurogenesis in old mice.
Fig. 1: 4D increases NSC expansion and neurogenesis throughout life.
a Scheme depicting the GFP and 4D viral constructs and experimental approach to increase NSC expansion and neurogenesis.
Temporal control of transgenes expression was achieved by delivering lentiviruses to nestin::CreERt2 mice (4D ON) with tamoxifen being later used to delete the LoxP-flanked 4D cassette (4D OFF) together with the nuclear localisation signal (nls) of GFP (or only the nls in control, GFP viruses).
Effects on cell types, nuclear to cytoplasmic redistribution of GFP and neurogenic markers used in this study are depicted in the cartoon simplifying the neurogenic lineage from stem and progenitor cells (NSC) to newborn and mature neurons.
b–e Experimental layouts (top), fluorescence pictures and quantifications (middle/bottom) of cell types identified upon immunohistochemistry for neurogenic markers (as indicated) in the DG or subgranular zone (SGZ) of mice injected with GFP or 4D viruses and analysed at different times later, as indicated.
Insets (dashed boxes, b–d) are magnified and examples of cells scored indicated (arrowheads or dotted lines). Scale bars = 50 μm. Data represent mean ± SD as the proportion of cells scored within the GFP+ infected population or total numbers of cells per area (mm2) in control (black) or 4D (blue) mice; N = 3; n > 2000 (b–e) and >1000 (b, right); error bars = SD (except for e, GFP, 16 months: N = 2; bar = SEM). *p 1500 ripples (e, box–whisker plots of the 10–90% quantile). *p
The Science Behind How New Brain Cells Are Generated
PASIEKA / Science Photo Library / Getty Images
Conventional wisdom has long suggested that we cannot grow new brain cells; that we are born with all of the brain cells we will ever have and that once those gray cells expire, they're gone for good.
This belief was fueled, in part, by the fact that certain motor (movement) and cognitive (thought) functions tend to decline the older we get. But should this suggest that it's all downhill once we approach a certain age and that we have no choice but to wait for the inevitable decline?
While the vast majority of our brain's cells are formed while we are in the womb, there are certain parts of the brain that continue to create new neural cells during infancy. Until recent decades, however, the brain’s limited capacity to regenerate triggered the belief that neurogenesis—the birth of new brain cells—ceased soon after this stage.
However, research done over the last two decades has suggested that at least one part of the brain continues to create new cells throughout a person's lifespan.
During the late 1990s, researchers at Rockefellers University in New York City conducted studies in which marmoset monkeys were injected with a tracer chemical that could differentiate between slow-dividing mature brain cells and fast-dividing new ones. What they found was that the hippocampus (a region of the brain associated with memories, learning, and emotions) continued to create new cells without the constraint of age or time.
Later studies using carbon-14 dating (which evaluate the age and process of cellular development) confirmed that cells in the hippocampus, while continually dying, were quickly replaced by new ones. It is only by the formation of these cells that the hippocampus is able to maintain its central functions.
What it also showed us is that the number of new cells, and the frequency by which they are created, begin to decline with age. With that being said, the rate of decline wasn't seen to be consistent and could vary significantly from subject to subject.
The above research is considered important as is suggests that there are factors that can stimulate and inhibit the process of adult neurogenesis. It even hints at possible models for treating degenerative diseases, such as Alzheimer's and Parkinson's diseases, and even reversing damage caused by traumatic brain injury.
Among the factors that can potentially “amp up” this process, exercise has been considered an important one.
Early animal research conducted by scientists at the University of Chicago found that aerobic exercise led to both an increase in cell production in the hippocampus and increases in the amount of genetic information being encoded.
What this tells us is that not only does the function of the brain improve, the cells themselves are better able to store information for learning and memory.
Research from the University of Pennsylvania in 2010 reported that aerobic exercise among 120 older adults increased the actual size of the hippocampus by two percent and effectively reversed the aging-related cell loss by one to two years.
In addition to exercise, scientists have found that enriched learning environments can also contribute to the survival of old cells and the production of new ones. In short, it is suggested that the more you exercise your brain, the more you will be able to maintain optimal brain function.
On the flip side, there are factors that directly undermine neurogenesis. Chief among these is age. We know, for example, that by the time many adults reach their 80s, as much as 20 percent of the neural connections in the hippocampus will be lost.
Recently, a new study performed at the University of California at San Francisco failed to demonstrate the development of new neurons in the hippocampus of almost 30 adult patients, fueling the controversy of whether neurogenesis in adults does indeed occur.
Future research with a large number of patients and the development of techniques that allow for imaging of new neurons in the living brain will be necessary to definitively confirm or refute the theory of neurogenesis in adults. This ongoing controversy should not discourage you from exercising physically and mentally—even if it does not help neurogenesis, its effects on your overall health are incontestable.
Thanks for your feedback!
What are your concerns?
Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
Ernst A, Frisén J. Adult neurogenesis in humans- common and unique traits in mammals. PLoS Biol. 2015;13(1):e1002045. doi:10.1371/journal.pbio.1002045
Erickson KI, Voss MW, Prakash RS, et al. Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci USA. 2011;108(7):3017-22. doi:10.1073/pnas.1015950108
Sorrells SF, Paredes MF, Cebrian-silla A, et al. Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults. Nature. 2018;555(7696):377-381. doi:10.1038/nature25975
19 Factors that May Increase Neurogenesis Naturally | Nature Knows
Some scientists think that neurogenesis may improve memory and help with anxiety and depression , though this is still uncertain. One thing’s for sure: the brain continues to birth new neurons throughout life. Read on to learn what may increase neurogenesis.
Can Certain Factors Increase Neurogenesis? If your goal is to increase neurogenesis to improve your brain- or mood-related issues – including those of depression, anxiety, or traumatic brain injury – it’s important to talk to your doctor, especially your mood is significantly impacting your daily life. Your doctor should diagnose and treat the condition causing your symptoms.
The existing evidence does not suggest that reduced neurogenesis causes any disease.Additionally, changes in brain chemistry are not something that people can change on their own with the approaches listed below. Instead, the factors listed here are meant to reduce daily stress and support overall mental health and well-being.
Therefore, you may try the additional strategies listed below if you and your doctor determine that they could be appropriate . None of these strategies should ever be done in place of what your doctor recommends or prescribes.We’re providing a summary of the existing research below, which should guide further investigational efforts.
The studies listed in this section were mostly done in animals and should not be interpreted as supportive of any health benefit in humans. 1) Exercise Research suggests that aerobic exercise increases the number of new neurons in the hippocampus and increases hippocampal volume [ 1 , 2 ].Running doubled the number of new cells in the hippocampus of mice [ 3 ].
One study found that aerobic exercise increased hippocampal volume in 120 elderly adults with dementia [ 4 ]. 2) Mental Activity Learning new skills (particularly challenging ones) increases the survival of new neurons in the hippocampus, according to some recent studies [ 5 ].
Scientists think that the hippocampus shrinks with age, and engaging in a complex mental activity is associated with less shrinkage [ 6 , 7 ]. 3) Sleep Short-term sleep deprivation (less than one day) has little effect on neurogenesis [ 8 ].However, chronic sleep deprivation seems to reduce neurogenesis by increasing levels of stress hormones [ 9 ].
Researchers consider that adequate sleep increases neurogenesis by lowering TNF-α and stress hormones [ 9 ]. 4) Meditation Stress is thought to be one of the main factors that decrease neurogenesis in the adult brain [ 10 , 11 , 12 ].Both physical and social stresses appear to decrease hippocampal neurogenesis [ 13 , 14 ].
According to limited research, meditation may increase the size of the hippocampus. Scientists think that stress reduction may underlie neurogenesis [ 15 , 16 ]. 5) Sexual Activity Sexual activity can also help relieve stress, but animal studies suggest it may also increase neurogenesis. Scientists found this with both acute and chronic sexual activity in rats [ 17 ].
Sex prevented a decrease in neurogenesis and improved memory in chronically-stressed mice [ 18 ]. 6) Flavonoids Flavonoids are a group of compounds found in most fruits and vegetables. Cocoa flavonoids seemed to build up in the hippocampus and protect the brain in animal models of aging, dementia, and stroke. Human evidence is lacking [ 19 ].
Blueberries and oolong and green teas are rich in flavonoids; they also increase neurogenesis in the hippocampus in animal experiments [ 20 , 21 ]. animal and cellular studies, researchers hypothesize that several flavonoids may support brain health by [ 22 , 23 ]:
However, human data are lacking to back these mechanisms up.
7) The LMN Diet The LMN diet is a patented Medittarenean- diet rich in polyphenols, polyunsaturated fatty acids, and soluble fiber [ 27 ].The LMN diet increased neurogenesis in mice, presumably by increasing precursor cells and mature neurons [ 28 ].This diet also appeared to increase neurogenesis in a mouse model of Alzheimer’s.
The researchers claimed it delayed the formation of amyloid plaques in the hippocampus and improved cognitive function [ 29 ].Nonetheless, human studies are lacking. Plus, the main author of the studies hold the patent for the LMN diet, opening room for bias [ 27 ].
8) Omega-3 Fatty Acids The omega-3 fatty acid DHA increased the formation of new connections in the hippocampus in gerbils [ 30 ].Increased hippocampal neurogenesis via omega-3 fatty acids has been proposed as a way to prevent PTSD , but this hasn’t been proven in humans. More research is needed [ 31 ].
9) Coffee and Tea (Chlorogenic acid) Chlorogenic acid is found in coffee and black tea . Scientists are investigating whether it promotes hippocampal neurogenesis in cells, along with its by-product m-coumaric acid [ 32 ].Chlorogenic acid also seems to help protect the hippocampus and improve memory in animals, yet clinical trials have not explored this compound [ 33 , 34 ].
10) Ketogenic Diets? Ketogenic diets are low-carb and high-fat, and they are claimed to induce the body to burn fat as its primary fuel source.One group of researchers found that a ketogenic diet increased neurogenesis in mice with epilepsy [ 35 ].However, another study reported that a ketogenic diet had no effect on neurogenesis in adult rats [ 36 ].
Therefore, additional research is needed to determine whether–and what type of–ketogenic diets affect neurogenesis, particularly in humans. Herbs and Supplements that May Increase Neurogenesis Speak with your doctor before taking any supplements. Make sure to let them know about any prescription or over-the-counter medication you may be taking, including vitamins and herbal supplements. Remember that dietary supplements have not been approved by the FDA for medical use. Supplements generally lack solid clinical research. Regulations set manufacturing standards for them but don’t guarantee that they’re safe or effective. 11) Resveratrol In animals and cells, resveratrol appeared to increase the birth of new neurons [ 37 ].Scientists hypothesize it might increase angiogenesis (the formation of new blood vessels) and levels of growth factors that are associated with neurogenesis. Theoretically, these changes may lead […]
Read more at selfhacked.com
Sharing is caring!
The Magic of Neurogenesis: How to Help Your Body Make New Brain Cells
According to the latest findings, you can boost neurogenesis. Pixabay
Many people think that their adult brain is not capable of generating new cells.
That’s it. Done. From now on, it will only get worse. And if you drink too much alcohol, or even watch too much Netflix, you will “kill” those neurons of yours for good.
Although aging or heavy alcohol consumption may contribute to deterioration of our brain health, the reality is much more complex.
For a long time, it was believed that brains of grown-ups couldn’t regenerate and replace dead or damaged cells. As late as 1998, a duo of scientists Peter Eriksson from Sweden and Fred Gage from the USA presented their discovery that human beings are capable of growing new brain cells throughout their whole lives.
The birth of neurons from stem cells is called neurogenesis and in babies, most of the job is done before they leave their mommy’s belly. After birth, this process is restricted to two areas:
Olfactory Bulb — a structure of the forebrain responsible for the sense of smell
Hippocampus — a seahorse-shaped structure that is located within the temporal lobe of the brain (just above your ears) and is important for learning, formation of memory, regulation of emotions, and spatial navigation.
In patients with Alzheimer’s disease, for example, the hippocampus is one of the first areas that get affected. The hippocampus is also associated with many other mental disorders. Investigations into the link between neurogenesis and depression indicate that production of new brain cells is impaired in depressed patients.
As expected, the discovery of neurogenesis in adult individuals has raised questions about how we can directly encourage the development of new neurons. Is it possible to heal our own brains?
Research and some studies that have been conducted since prove that we can indeed play an active role in promoting production of new brain cells, and as a result improve our mood, memory, and learning skills. According to the latest findings, you can boost neurogenesis if you pay attention to these:
Yes, that’s right. If you decide to go for a run today, you will not only improve your general health, but you will also help your brain produce new brain cells.
According to the study in rats published last year (2016) in the Journal of Physiology, physical exercise enhances neurogenesis if it’s aerobic and sustained.
On the other hand, anaerobic resistance training doesn’t result in higher production of neurons in the hippocampus, even though it may have a positive effect on physical fitness.
High-intensity interval training (HIT) showed only a very little increase in the number of new neurons, compared to the sedentary lifestyle, possibly due to the related stress that tends to reduce neurogenesis.
Scientists believe the effects of exercise on neurogenesis, as they were modeled on animals, should have a similar impact on a human brain. Dr. Wendy A.
Suzuki, Professor of Neural Science and Psychology at New York University, has dedicated her recent work to how aerobic exercise improves memory and learning.
In her book titled Happy Brain, Happy Life the neuroscientist talks about the connection between exercise and the ability of our brain to perform better.
Nothing is closer to the truth than the saying: “You are what you eat.” The composition of your diet is not only important for you in order to stay fit and look slim, but also for your mental health.
In 2009, Doris Stangl and Sandrine Thuret published their research findings on how our diet affects the formation of new cells in the adult human brain. According to these, diet can impact neurogenesis at four levels: through calorie restriction, meal frequency, meal texture, and meal content.
Studies show that caloric reduction leads to an extended lifespan, significantly increases production of new neurons, and reduces the risk of neurological diseases, such as stroke, Alzheimer’s disease, or Parkinson’s disease.
Experiments with rodents indicated that the positive effects of dietary restriction could be achieved by both daily caloric reduction (50–70% of the normal diet) and intermittent fasting (alternating schedule of eating and fasting).
Therefore what really matters is the net cutback on how much you eat.
When there’s no reduction in calorie intake, neurogenesis can be promoted by extending the time between meals.
Japanese scientists went even further and showed that food texture also makes some difference. Soft diet apparently impairs neurogenesis, as opposed to hard diet that requires chewing, even though the whole mechanism is still not completely clear.
Apart from the overall calorie intake, the important factor for stimulation of neurogenesis is the proportion and type of fat in your diet.
Laboratory tests point to the fact that excessive consumption of meals that contain high amounts of saturated fat (animal fat products, coconut oil, palm oil) significantly decreases the number of newly generated cells in the hippocampus.
There is plenty of evidence that proves the correlation between a diet rich in saturated fats and diminished neurogenesis, which may augment the risk of depressive and anxiety disorders.
In essence, it means that too much butter, cheese, bacon, or Nutella can lead not only to obesity and cardiovascular diseases but also to brain damage.
In contrast stands the type of fat found in salmon, tuna, walnuts, or flax seeds — omega-3 fatty acids — that have been shown to promote the production of new neurons.
These nutrients are important for our whole body in a variety of ways, but they play a truly critical role in development and functioning of our brain.
Some studies even indicate that the beneficial effect of omega-3 fatty acids on neurogenesis in the hippocampus could help treat and prevent age-related memory weakening, depression, or neurodegenerative disorders, such as Alzheimer’s disease.
In summary, if you eat foods high in omega-3 fatty acids, you genuinely help your brain work well.
According to some studies, neurogenesis can be also reinforced by certain dietary substances, such as flavonoids, found in blueberries and cocoa, resveratrol, found in red wine, or curcumin, found in the turmeric spice. So a glass of cabernet, a bite of dark chocolate, or a bowl of yellow curry can be a nice treat for your brain.
On the contrary, it appears that chronic sleep deprivation and stress (including early-life and pregnancy trauma) inhibit the production of new brain cells in adults, which in turn causes deterioration of our cognitive functions and overall mental health.
Being in control of our life starts with being in control of our body. Author provided
Most of us take it for granted that we cannot succeed either in our life or our career without a perfectly functioning brain. However, when something is wrong, we refuse to assume our own responsibility. Sometimes we blame genetics or our education. Often, we look for strong medications, rather than opting for better food and a few more hours of sleep.
Being in control of our life starts with being in control of our body. It’s fantastic to realize that there’s magic happening inside our heads, and we can help it with as little as delivering enough oxygen and the right nutrients to our brain cells.
Kristyna Z. is an entrepreneur coach and a co-founder of MAQTOOB. Her book is for mindful entrepreneurs is just being born.
“,”author”:”Kristyna Zapletal”,”date_published”:”2017-03-13T15:00:26.000Z”,”lead_image_url”:”https://observer.com/wp-content/uploads/sites/2/2017/03/emoji-1913846_1920.jpg?quality=80&strip”,”dek”:null,”next_page_url”:null,”url”:”https://observer.com/2017/03/the-magic-of-neurogenesis-help-your-body-brain-cells-development-entrepreneurship-health-neuroscience/”,”domain”:”observer.com”,”excerpt”:”We can indeed play an active role in promoting production of new brain cellsâand as a result improve our mood, memory, and learning skills.”,”word_count”:1209,”direction”:”ltr”,”total_pages”:1,”rendered_pages”:1}