The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 16 No. 7 • August 2013


Neurogenesis

Lithium Restores Neurogenesis in Mouse Model
of Down’s Syndrome, Correcting Cognitive Defects

A remarkable feat of pharmacological treatment to induce adult neurogenesis in a mouse model of Down’s syndrome1 suggests the possible correction of cognitive impairments in humans with the disorder.

Cognitive defects are the most prominent features of human Down’s syndrome, resulting from three copies of Chromosome 21 rather than the normal two copies. One would think that to correct the features of the disease it would be necessary to administer genetic therapy. However, researchers publishing a new paper1 found that treatment with the mood stabilizer lithium markedly increased adult neurogenesis in the subventricular zone (SVZ) of the brain as well as restoring brain volume in several areas where it is smaller than in normal mice.

In individuals with Down’s syndrome, brain hypotrophy is particularly evident in the cerebral hemispheres, frontal lobe, temporal cortex, hippocampus, and cerebellum and shows up early in development.1

The Down’s syndrome mouse is produced by creating three copies of a distal region of the mouse chromosome 16—“a region that shows perfectly conserved linkage with human chromosome 21.”1 Treatment with lithium resulted in an 85% increase in the pool of proliferating cells in the Down’s syndrome mice, while the pool was increased in the normal mice by 54%. “In the [Down’s syndrome mouse] the number of Brdu+ [label indicating proliferation] cells became similar to that of the untreated euploid [normal] mice.” DOSAGE: The DS female mice were, starting from the age of 12 months, treated with lithium contained in their food pellets at 2.4 g of Li2CO3/kg of food for one month. This dose scales to approximately that used to treat mania and bipolar disorder in humans. Since renal excretion varies, doses would need to be individualized based on readily available blood tests.

The authors conclude in a carefully worded summation: “If such a treatment will be proven to be effective [in humans], this might open the way to possible therapeutic intervention practicable by human subjects, aimed at correcting defects in brain development in DS individuals.”

LITHIUM AS AN ESSENTIAL NUTRIENT

A 2012 paper2 provided detailed information on the presence of lithium in drinking water and vegetation and on its essentiality in a large number of animal and human studies.

The review reported that there is a wide variation in the amount of lithium found in drinking water, spring water, spa water and bottled water. One study of 132 brands of bottled water from 28 countries found lithium concentrations ranging over 5 orders of magnitude (from 0.057 to 5,460 μg/l. “Li concentrations of 8.7 mg/l and of >9 mg/l have been reported for the Friedrich-Quelle, a famous spring in Baden-Baden/Germany, and for the spa water in Pompeya/Argentina, respectively.”2

“The long-term consumption of low-Li drinking water is regarded as a risk factor for higher incidences of suicides, homicides, and crimes as shown in several studies. For example, in 24 counties in Texas/USA with a total population of 6 million (>60% of the state population), during a 2-year study (1967-1969), a significantly inverse relationship between 1) Li concentration of local drinking water, 2) Li concentrations of the urine among the respective residents, and 3) mean annual rainfall amounts in the respective county sites and 1) state mental hospital admission rates, 2) admitting rates for four major mental disorders (psychosis, neurosis, schizophrenia, personality problems), 3) homicide rates, and 4) road distance from resident county to nearest state mental hospital was found (p ≤ 0.05 to ≤ 0.001). The Li levels in drinking water were classified into 4 groups: <11.0; 11.0–29.9, 30.0–69.9; >70.0 μg/l.”2

A second study reported in the review2 included 27 counties and lasted for 10 years (1978–1987) and found that that the incidence rates of suicide, homicide, and rape were significantly higher in counties whose drinking water contained low (0–12 μg/l) and medium (13–60 μg/l) lithium concentrations than in counties whose drinking water had high Li concentrations (79–160 μg/l)(p<0.01). They also found associations with the rates of robbery, burglary, and theft significant at p<0.05. These are really remarkable differences that suggest improved mental function with low dose lithium.

On the basis of these and many other studies, the basic requirement of lithium in humans has been assessed at 1 ug/kg. body weight/d in humans derived from intake data in Germany, thus, the lithium requirement for an adult of 70 kg body weight would be 70 μg/d. In another assessment study, Schrauzer suggested a provisional recommended dietary allowance (RDA) of 1 mg lithium/day for an adult of 70 kg body weight.3

References

1. Bianchi et al. Lithium restores neurogenesis in the subventricular zone of the Ts65Dn mouse, a model for Down syndrome. Brain Pathol. 20:106-18 (2010).
2. Schafer. Evaluation of beneficial and adverse effects on plants and animals following lithium deficiency and supplementation, and on humans following lithium treatment of mood disorders. Trace Elem Electrolytes. 29(2):91-112 (2012).
3. Schrauzer. Lithium: occurrence, dietary intakes, nutritional essentiality. J Am Coll Nutr. 21:14-21 (2002).

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