The 'selfish brain' is regulated by aquaporins and autophagy under nutrient deprivation

[zc_hl]

Starvation in Man (https://www.nejm.org/doi/full/10.1056/N ... 3192821209)

"Because of the small excretion of urea (normally the major osmotic solute), there is very little need for water excretion, and urine volume may fall to 200ml per day. Thus, a fasting man need drink very little water, the water produced by metabolism approximating that lost in urine and that lost by evaporation from skin and lungs. Therefore, as long as he is in a temperate and humid environment, his water needs are minimal when he is starving, another excellent adaptation for survival, particularly in a primitive environment. "

[zc_hl]

Deuterium-Depleted Water Influence on the Isotope 2H/1H Regulation in Body and Individual Adaptation
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723318/

The sensitivity of the central nervous system to fluctuations in the isotopic composition of water is confirmed by experiments on the Wistar rats, which consumed water with δ2H within the range from −827‰ to −807‰. They demonstrated, in comparison with the rats who drank water with δ2H within the range from −69‰ to −37‰, the reduction of fear and anxiety in unfamiliar environment. In another research by the same authors the Wistar rats who consumed DDW showed an improvement in long-term memory and absence of short-term memory differences compared with animals that consumed water with a natural concentration of deuterium.​


To influence nervous tissue, water with modified isotopic composition can affect the aging rate of the whole organism. For example, white outbred female rats of presenile age (20–22 months) consumed DDW (δ2H = −704‰) as drinking water for five weeks and it led to development of the expressed geroprotective effect, manifested in the appearance of recovery signs in the estrous cycle, as well as in the improvement of coat condition compared with the same parameters in animals exposed to drinking water with δ2H = −37‰. At the same time the rats that drank DDW showed development of persistent anti-stress adaptive responses of their bodies to calm and enhanced activation as well as increase in bactericidal activity of their skin. Thus in experiments on mammals the direct confirmation of DDW’s geroprotective properties was obtained, and the relation between geroprotective and anti-stress effects was shown when DDW was used in the drinking ration.​


In addition to the drinking diet, the proportion of proteins, lipids and carbohydrates in the consumed food, which proportion is associated with oxidation of organic compounds in mitochondria. At the same time, the greatest decrease of deuterium content in intracellular water is achieved with increase of lipid-containing nutrients proportion in the diet.​


The DDW also can be used as synergistic anti-inflammatory agent against sepsis with modulated oxidative stress/antioxidant parameters, as adjuvant to conventional anticancer treatment, moreover, DDW drinking is effective against hypoxia of the central nervous system and for the prevention of individuals with depression.

Also the influence of DDW for nucleic acids is noted, including its ability to increase the intensity of mitochondrial activity and autophagy as well as to alter and miRNA transcriptomic pattern in cells of some tumors. Due to this, DDW can be used as adjuvant therapy for cancer treatment.

​

Best way to reach a state of deuterium depleted water in cells could be to eat a high fat diet and limit water consumption.

[zc_hl]

Therapeutic Approaches to Delay the Onset of Alzheimer's Disease (https://www.hindawi.com/journals/jar/2011/820903/)

"Osmolytes are brain metabolites which accumulate in tissues at relatively high concentrations following stress conditions. Osmolytes enhance thermodynamic stability of proteins by stabilizing natively-folded protein conformation, thus preventing aggregation without perturbing other cellular processes. Osmolytes may inhibit the formation of Aβ oligomers in vivo, thus preventing the formation of soluble oligomers. The potential significance of combining diaminophenothiazins and osmolytes to treat AD is discussed."

Osmolytes might be synthesized and used during water restriction/osmotic stress.

[zc_hl]

The effects of fasting during Ramadan on the concentration of serotonin, dopamine, brainderived neurotrophic factor and nerve growth factor (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5505095/)

"According to our investigation, the plasma levels of serotonin, BDNF and NGF were significantly increased during fasting month of Ramadan. In detail, the levels of these factors were increased in 14th and 29th day test groups compared to controls (P<0.05). Moreover, these levels were significantly increased on the 29th day compared to the 14th day test groups, but there were no differences between dopamine levels in all groups. Furthermore, the results obtained in women’s groups were the same as those obtained in previous groups. Our findings suggest that plasma levels of serotonin, BDNF and NGF were significantly increased during fasting month of Ramadan."

Average BDNF level went from 221 (+/- 3) pg/mL to 417 (+/- 7) pg/mL.
Not sure that the serotonin increase is a good thing though.

[SusanJ]

Interesting, because during Ramadan, people break their fasting after sundown, whereas some other recent studies showed that eating earlier in the day might be better for intermittent fasting. And Bredesen recommends stopping eating 3 hours before bedtime. Thanks for sharing!

[Jafa]

Hi Susan, could you post the references to recent studies on shorter fasts. This is quite topical for me at present. I recently had a gastroscopy after developing digestive problems and have mild gastritis in most areas of the stomach. I am trialing a course of acid suppression medication to try and calm things down. I am considering options around diet and fasting if things don’t settle. With my goal of increasing weight I may have overdone the dark chocolate and nuts/nut butters. Also eating larger meals. Recommendations are little and often, unlikely to be recommended for glycaemic control though! I lasted two days without coffee and was like a bear with a sore head. Also more forgetful and unfocused. Thanks Susan, I hope you are doing okay.

[zc_hl]

You may be interested by this one too:

Intermittent fasting from dawn to sunset for 30 consecutive days is associated with anticancer proteomic signature and upregulates key regulatory proteins of glucose and lipid metabolism, circadian clock, DNA repair, cytoskeleton remodeling, immune system and cognitive function in healthy subjects (https://www.sciencedirect.com/science/a ... 1920300130)

"Intermittent fasting from dawn to sunset results in a serum proteome protective against cognitive dysfunction, Alzheimer's disease and several neuropsychiatric diseases

HOMER1 gene is abundantly expressed in the brain [27]. Alterations in HOMER1 levels in the hippocampus and cingulate gyrus were reported in schizophrenia, major depression, and bipolar disorder [65]. HOMER1 variants were reported in various neurological disorders, including Alzheimer's disease, schizophrenia, chronic pain, traumatic brain injury, and drug-induced addiction [66]. HOMER1 knockout mice were shown to have neurochemical and behavioral abnormalities similar to the abnormalities observed in schizophrenia. [67] Amyloid precursor protein and presenilin 1 transgenic mice as an Alzheimer's disease model was shown to have reduced HOMER1 mRNA expression [68]. In addition to these reports, HOMER1 expression was found to be increased in the hippocampus post-synaptic densities of Long Evans aged rats with unimpaired memory compared with those with impaired memory[69]. We found an average 25 fold increase in the HOMER1 GP level at the end of 4th week during 30-intermittent fasting compared with the level before 30-day intermittent fasting. APP, the precursor of amyloid β, appears to play a significant role in the development of Alzheimer's disease [27]. APP was proposed to trigger atherothrombosis after the accumulation of amyloid β peptides in the cerebral vessels in Alzheimer's disease [70]. We observed a significant reduction in the APP GP level at the end of 4th week during 30day intermittent fasting compared with the level before 30-day intermittent fasting. ARPP-21 that is abundantly expressed in the brain, is another gene that plays a significant role in the development of Alzheimer's disease [27]. A genome-wide study conducted among subjects with Alzheimer's disease showed a single-nucleotide polymorphism (SNP) located proximal to the ARPP-21 gene. [71] We found a significant reduction in the ARPP21 GP level at the end of 4th week during and one week after 30day intermittent fasting compared with the level before 30-day intermittent fasting. According to a genome-wide study conducted among 1527 patients with bipolar disorders (1579 controls) and 1159 patients with recurrent unipolar depression (2592 controls), a SNP located in the SYNE1 gene was significantly associated with the risk of bipolar depression and recurrent major depression. [72] We found a significant reduction in the SYNE1 GP level one week after 30-day intermittent fasting compared with the level before 30-day intermittent fasting. Altogether, these findings suggest that 30-day dawn to sunset intermittent fasting can have implications in the improvement of cognitive function, prevention, and treatment of Alzheimer's disease and several neuropsychiatric disorders, including major depression, bipolar disorder, and schizophrenia."

[zc_hl]

Hi,

It's been a long time since I haven't made an update (that nobody was really waiting for ) to this thread.

Here is an hypothesis ("gathered" from multiple publications by myself) about a link between the glymphatic system (which may have an important role regarding Alzheimer) and water homeostasis (via the AQP4 aquaporin/NFAT5 link):
https://open.substack.com/pub/leadthewa ... tic-system

Note/caveat: research on the glymphatic system is still being made and I've read contradictory statements, especially on the role of AQP4.

I think it compliments well the publications posted which showed that autophagy might be increased (in rats brain) during a dry fast and the result about pro-amyloid beta genes whose expression seems to be down-regulated during Ramadan.

What do you think about it? Is there a credible mechanism here?

Have a good day.