Category Archives: Lithium

Lithium: Part 1

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PROTECT AND RENEW YOUR BRAIN

Like you, I want to keep my mind functioning well for as long as I possible, so (among other things) I’ve been taking a lithium supplement every day for several years. I have reviewed both the rapidly increasing recent research concerning lithium, as well as research about lithium going back decades, and I’m convinced that lithium is an anti-aging nutrient for human brains, an agent which can both protect and renew human brain cells. There are also very strong reasons to believe that lithium therapy will slow the progression of serious degenerative mental problems including Alzheimer’s disease, senile dementia, and Parkinson’s disease.

Lithium isn’t a drug. It’s a mineral, part of the same “family” of minerals that includes sodium, potassium, rubidium, and cesium. In the 1930s and 40s, lithium chloride was sold in stores as a “salt substitute”, but (as frequently happens) some users used ‘way too much and suffered toxic overdoses. Fortunately, lithium toxicity is both entirely preventable, and treatable if it ever occurs, but more about that later.

Do you remember Hercule Poirot, Agatha Christie’s famous fictional detective, and his incessant concern for his “little grey cells?” Here’s a headline (from the Lancet, no less) that would make Hercule sit up and take notice: “Lithium-induced increase in human brain grey matter”. Medical students are still told that once our brains mature, it’s all downhill from there on. Decades of X-rays and brain scans have repeatedly shown that brains shrink measurably with aging. But reporting in Lancet, Wayne State University (Detroit) researchers reported: “rodent studies have shown that lithium exerts neurotropic [nerve growth promoting] or neuroprotective effects. We used…magnetic resonance imaging…to study pharmacologically induced increase in grey matter volume in patients with bi-polar mood disorder. Grey-matter volume increased after 4 weeks of treatment[1].”  Eight of ten individuals who took lithium showed an increase in brain grey matter (again, in just 4 weeks) which averaged 3%.

This research used high-dose lithium. I’m certainly not using that amount, nor do I recommend it. I’m happy to tell you that epidemiologic studies done years ago have shown that very low amounts of lithium can also measurably influence brain function for the better. “Prescription” quantities of lithium just aren’t necessary for “everyday” brain cell protection and brain cell re-growth.

PROTECTION AGAINST BRAIN CELL INJURY

Much of the recent expansion of pioneering research work in lithium and brain protection has been led by researchers from the National Institutes of Mental Health (USA). These researchers (and others) have found that lithium protects brain cells against damage caused by toxic molecules that are naturally formed in the course of brain metabolism[2],[3],[4],[5],[6]. Since these “normal” toxic molecules (sometimes called “excitotoxins”) are produced in variable quantities in your brain every day of your life, it’s not a surprise that there might be an “eroding away” of brain mass over time.

Overactivated N-methyl-D-aspartate (NMDA) receptors, are another well known “pathway” to brain cell injury. Another neuroprotective action of lithium is inhibition of NMDA receptor overactivity2 has been found to over-activation of these receptors,

From this and other research evidence, it appears that lithium can protect against “normal brain erosion” and shrinkage that would otherwise occur over the course of our lives.

Lithium also protects against exogenous (taken in from the outside, not formed normally in the course of metabolism) molecules such as patent medications used in psychiatry. Anti-convulsant medications induce abnormal levels of brain cell death. Lithium “significantly” protects against this type of cell death; this effect has been called “robust”[7] (a term which scientists use to mean “it really works”!). Many “older-generation” psychiatric drugs caused a movement disorder called “tardive dyskinesia”. Lithium was found to markedly reduce this toxic effect[8]. Because of lithium’s general neuroprotective effect, researchers have recently suggested that “the use of lithium as a neurotrophic/neuroprotective agent should be considered in the long term treatment of mood disorders, irrespective of the “primary” treatment modality being used for the condition[9]. Translation: lithium should be used along with any patent medicine being used for depression, anxiety, or any other “mood-altering” reason, since it will protect brain cells against their unwanted toxic effects. (The researchers didn’t say so, but I will: any list of “mood altering substances” should include alcohol, tobacco, caffeine, “uppers”, “downers”, and for those who do inhale, marijuana. It’s obvious to anyone that some of these substances cause brain damage with medium to long-term abuse.)

BRAIN CELL RE-GROWTH

Lithium increases production of a major brain protective protein called “bcl-2” in both human and animal brain cells. According to one reviewer[10]: “increased bcl-2 levels….have demonstrated an increase in the regeneration of mammalian CNS [central nervous system] axons [projections of nerve cells which contact and transmit messages to other nerve cells].

In addition to helping to re-growing portions of nerve cells, lithium may help to generate entire new dells. One group of researchers has very recently reported that lithium also enhances nerve cell DNA replication[11]. DNA replication is a first step in the formation of a “duplicate” new cell of any type.

INCREASING BRAIN CELL VIABILITY AND FUNCTION

N-acetyl-aspartate (NAA) is a brain cell molecule which research scientists presently consider to be a “marker” for the viability and healthy function of brain cells. (NAA can be detected with MRI scans, making it possible to study in living humans.) A decrease in NAA is thought to reflect decreased nerve cell viability, decreased function, or even nerve cell loss[12]. In a “blind” study of 19 research volunteers (12 with manic-depressive illness, 7 healthy controls) given four weeks of lithium, 14 were found to have a significant increase in NAA, 1 had no change, and 4 had a small decrease. (There was no significant difference between the reponse of those with manic-depressive illness and the healthy control group.) The researchers wrote: “these findings provide intriguing indirect support for the contention that, similar to findings in rodent brain and human neuronal cells in culture, chronic lithium increases neuronal viability and function in the human brain….[13]

BRAIN CELL COMMUNICATION

Communication between brain cells and networks of brain cells is called “signalling”. Lithium has been found necessary for at least two signal-carrying pathways[14]. Researchers have also reported that lithium may actually help to repair abnormally functioning signalling pathways “in critical areas of the brain[15]”.

PROTECTION AGAINST BRAIN DAMAGE FROM “STROKES”

When a clot or other obstruction occurs in a blood vessel serving the brain, a reduction in blood flow in blood flow occurs. If it’s bad enough, the lack of blood flow will cause an “ischemic” stroke, and death of a variable area of brain cells. Research in experimental animals with deliberately induced ischemic strokes has shown that the areas of cell death are reduced by lithium, and that the areas of cell death are lessened[16],[17].

One group of researchers blocked a brain artery in rats. Some were pre-treated with lithium for 16 days, others were not. They reported that the area of cell death was reduced by an average 56% in the lithium pre-treated rats, and that neurologic deficits in these rats were significantly less[18].

SPATIAL MEMORY

“Sense of direction” is termed “spatial memory” in scientific lingo. One common type of experiment on spatial memory involves observing animals in mazes. The maze-navigating ability of lithium treated and untreated rats was observed over four months. It was found that lithium improved spatial memory (ability to remember how to navigate the maze) with as little as 24 hours of lithium exposure. Although only one research group has published on this possible effect of lithium[19], it’s another intriguing possibility.

 

ALZHEIMER’S DISEASE: PROTECTION AND POSSIBLE TREATMENT!

A new patent medication has recently been “approved” in Europe for the treatment of Alzheimer’s disease. It’s said to “work” by protecting brain cells against damage by a major “excitotoxin”, glutamate. Protection against glutamate induced nerve cell damage is one of the now well known actions of lithium! If it’s true that this newly “approved”  patent medication slows the progress of Alzheimer’s disease in this way, then unpatentable lithium should slow Alzheimer’s disease progression, too.

There are many other “basic science” research findings that suggest very strongly that lithium will both protect against potential Alzheimer’s disease and slow the progression of existing cases. “Beta-amyloid peptide” is a “signature protein” involved in Alzheimer’s disease: the more beta-amyloid protein, the worse the Alzheimer’s becomes. Researchers have reported that lithium inhibits beta-amyloid secretion[20], and also prevents damage caused by beta-amyloid protein once it’s been formed[21],[22],[23]

Over-activation of a brain cell protein (“tau protein”) contributes to neuronal degeneration in Alzheimer’s disease, as does the formation of “neurofibrillary tangles” (under the microscope, abnormal tangles of tiny fibers inside nerve cells). Lithium inhibits both of these nerve-cell damaging problems[24],[25].

You’ve likely read that individuals with Alzheimer’s disease usually have excess aluminum accumulation in brain cells. While it’s not yet known whether this excess aluminum is a cause, an effect, or just co-incidental, most health-conscious individuals take precautions to avoid ingesting aluminum. Unfortunately, it’s completely impossible to avoid all aluminum, since it’s naturally present in variable concentrations in nearly all foods. Lithium can help protect your brain against aluminum; in 1977, a researcher wrote that “lithium continues to be the most effective electrolyte for aluminum detachment”; that’s still the case today. Lithium also helps to “chelate” aluminum so that it can be more easily be removed from the body, and it inhibits formation of abnormal “crosslinks” caused by the aluminum[26].

SENILE DEMENTIA

Although Alzheimer’s disease and senile dementia are not the same (for example, some senile dementia appears to be caused by atherosclerosis in blood vessels to the brain), there are many overlapping degenerative features shared by both. Reviewing all that researchers have found about lithium and brain protection, there’s every reason to expect that lithium will help prevent or slow the progression of senile dementia, too. One example, in cases progressive senility caused by over-all poor blood flow to the brain, lithium can slow the damage caused by this sort of “generalized ischemia”, too, not just the localized ischemia caused by a stroke.

HOW MUCH LITHIUM?

The amount of lithium required to help manic- depressive illness is quite high, ranging from approximately 90 to 180 milligrams of elemental lithium daily (from 900 to 1800 milligrams of lithium carbonate). Quantities of lithium in that range must be monitored closely to guard against overdose and toxicity. But large amounts aren’t necessary for “everyday” improvement of brain function. Epidemiologic studies have repeatedly shown that substantially lower amounts of lithium (in fact, “background” quantities of lithium naturally occurring in drinking water) can significantly affect brain function, lowering rates of of mental hospital admissions, violent crime, aggression, suicide, and drug addiction

The amounts of lithium I recommend for “brain anti-aging” range from 10 to 20 milligrams (of lithium, from lithium aspartate or lithium orotate) daily. (Rarely, I’ll recommend a bit more, up to 30 milligrams daily.) I’ve actually been recommending these amounts since the 1970s (for treatment of the problems we’ll review in next month’s Nutrition & Healing; see below) and at first was exceptionally cautious. I asked everyone to have regular “lithium level” blood tests and thyroid function tests (high-dose lithium therapy can be effective treatment for overactive thyroid, a topic we’ll cover next month). After a year or a little more, I quit asking for “lithium level” blood tests, since 100% of them came back very low. In approximately another year, I stopped requesting “routine” thyroid function tests, too, only doing one when I was suspicious of a potential problem. I’ve rarely found one.

So how do I know that 10 to 20 milligrams of lithium are actually enough to do any good? Because I’ve listened to many individuals tell me that (in addition to the “physical health” problem they were using lithium for) they could really tell a “mental health” difference too…less depression (in people who have no sign of “manic-depressive illness”), less unaccountable anger, and better mood even when no depression exists. Family members have made favorable comments along the same lines.

Are 10 to 20 milligrams of lithium daily enough for “optimal” brain anti-aging? At this time, I really don’t know, since there’s no controlled research about “low-dose” lithium. But if you’re interested in “brain anti-aging” and maintaining cognitive function for as long as possible, review this information with your physician…but make sure your physician is skilled and knowledgeable in nutritional and natural medicine! (If yours isn’t, see “Resources” on page 8.)

Lithium

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USING LITHIUM SAFELY:

PREVENTING AND REVERSING LITHIUM TOXICITY AND SIDE EFFECTS WITH ESSENTIAL FATTY ACIDS

     [My apologies to long-time Nutrition & Healing readers who’ve read this description before (June 1998). It’s repeated as a very necessary part of this month’s discussion of the “new” uses of lithium as an anti-brain-aging nutrient.]

Over a decade ago, a woman visited Tahoma Clinic on the advice of her psychiatrist. She was “severely bipolar”, requiring a maximum dose of lithium carbonate to keep her symptoms under control. Despite close monitoring of serum lithium levels to maintain a safe range, she was starting to show many signs of lithium toxicity, including hypertension, tremor, nausea, and proteinuria. She and her psychiatrist had tried other medications, but none provided the control of her bipolar symptoms that lithium did. As she asked: “Is there an alternative to either the psych ward or the medical wing?”

Fortunately, there was, and is. Without changing her lithium dose, she was asked to start on flaxseed oil, one tablespoon (15cc’s) three times daily along with 800 IU of vitamin E (mixed tocopherols). One month later, her blood pressure had normalized, her tremor and nausea were gone, and there was no further protein in the urine. Her bipolar symptoms remained under control. She was advised to cut the flaxseed oil to one tablespoon daily along with 400 IU of vitamin E. Several years later, her lithium toxicity hasn’t returned.

I’m grateful to Dr. David Horrobin (deceased April 2003) for the basic information about how to prevent and treat lithium toxicity, as illustrated by this case. During a years-ago lecture on fatty acid metabolism, he pointed out in passing that lithium could inhibit a vital step, but that this could be overcome by providing more “precursor” fatty acid to overwhelm this inhibition. This simple procedure works in vivo as well as in vitro.

To be “on the safe side”, a daily amount of flaxseed oil (or other essential fatty acid), along with vitamin E, should be recommended for anyone taking lithium. With low dose lithium, a teaspoonful or two daily is usually sufficient.

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NEXT MONTH: OTHER EFFECTS OF LITHIUM

Next month, in Lithium: Part 2, I’ll review lithium’s many other effects. Epidemiologic studies have shown that lower lithium levels are correlated with higher rates of mental hospital admissions, violent crime, aggression, suicide, and drug addiction. Lithium helps reduce alcohol consumption in some alcoholics, and helps elevate mood in depressed (not manic-depressive) relatives of alcoholics. It’s been successfully used to treat and/or prevent anorexia nervosa, cluster headaches, herpes infections, hyperthyroidism, fibromyalgia, gout, and familial Mediterranean fever. Lithium can raise low white blood cell counts, low platelet counts, and possibly even red blood cell counts. Lithium has been shown to lower blood sugar in some diabetics.


[1] Moore G J et al. Lithium-induced increase in human brain grey matter. Lancet 2000;356:1241-1242

[2] Chuang, De-Maw; Christ, Lori; Fujimaki, Koichiro; Hashimoto, Ryota; Jeong, Mi Ra Lithium-induced inhibition of Src tyrosine kinase in rat cerebral cortical neurons: A role in neuroprotection against N-methyl-D-aspartate receptor-mediated excitotoxicity. FEBS Letters 2003;538(1-3):45-148.

[3] Hashimoto, R.; Takei, N.; Shimazu, K.; Christ, L.; Lu, B.; Chuang, D. M. Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: an essential step for neuroprotection against glutamate excitotoxicity. Neuropharmacology 2002;43:1173-9

[4] Ren, M.; Kanai, H.; Chuang, D. M.; Chen, R. W.; Chalecka-Franaszek, E.; Qin, Z. H. Regulation of c-Jun n-terminal kinase (JNK) and p38 kinase in cultured brain neurons: Roles of glutamate and lithium. Society for Neuroscience Abstracts 2001;27(1):259.

[5] Chuang, De-Maw Lithium exerts robust neuroprotective effects in vitro and in the CNS in vivo: Therapeutic implications. Neuropsychopharmacology 2000;23(S2):S39.

[6] Nonaka, S.; Hough, C. J.; Chuang, D-M. Chronic lithium treatment robustly protects neurons in the central nervous system against excitotoxicity by inhibiting N-methyl-D-aspartate receptor-mediated calcium influx.Proceedings of the National Academy of Sciences of the United States of America 1998;95(5):2642-2647

 

[7] Nonaka, S.; Katsube, N.; Chuang, D-M. Lithium protects rat cerebellar granule cells against apoptosis induced by anticonvulsants, phenytoin and carbamazepine. Journal of Pharmacology and Experimental Therapeutics 1998;286(1):539-547

[8] Reda FA, Escobar JJ, Scanlan JM. Lithium Carbonate in the Treatment of tardive dyskinesia. Am J Psych 1975;132(5):560-562

[9] Manji, Husseini K.; Chen, Guang; Moore, Gregory J. Lithium up-regulates the cytoprotective protein Bcl-2 in the CNS in vivo: A role for neurotrophic and neuroprotective effects in manic depressive illness. Journal of Clinical Psychiatry 2000;61(9):82-96.

[10]Manji, Husseini K.; Chen, Guang; Moore, Gregory J. Lithium at 50: Have the neuroprotective effects of this unique cation been overlooked? Biological Psychiatry 1999;46(7): 929-940.

[11] Chuang, D.-M.; Hashimoto, R.; Kanai, H.; Leeds, P.; Senatorov, V. Lithium stimulates progenitor proliferation in cultured brain neurons. Neuroscience 2003;117(1):55-61.

[12] Tsai G, Coyle JT. N-acetyl aspartate in neuropsychiatric disorders. Prog Neurobiol 1995;46:531-540

[13] Moore GJ et al. Lithium Increases N-acetyl aspartate in the human brain: in vivo evidence in support of bcl-2’s neurotrophic effects? Biol Psych 2000;48:1-8

[14] Williams, R. S. B.; Harwood, A. J. Lithium therapy and signal transduction. Trends in Pharmacological Sciences 2000;21(2);61-64

[15] Lenox, Robert H.; Hahn, Chang-Gyu Overview of the mechanism of action of lithium in the brain: Fifty-year update. Journal of Clinical Psychiatry 2000;61 (Supplement 9):5-15.

[16] Williams, R. S. B.; Harwood, A. J. Lithium therapy and signal transduction. Trends in Pharmacological Sciences 2000;21(2);61-64

[17] Lenox, Robert H.; Hahn, Chang-Gyu Overview of the mechanism of action of lithium in the brain: Fifty-year update. Journal of Clinical Psychiatry 2000;61 (Supplement 9):5-15.

[18] Nonaka S, Chuang DM. Neuroprotective effects of chronic lithium on focal cererbral ischemia in rats. Neuroreport 1998;9(9):2081-2084

[19] Weeks, O. I.; Volmar, C. H. Lithium and spatial memory: A new pathway? Society for Neuroscience Abstracts 2001;27 (1) 845.

[20] Takashima, A.; Murayama, M.; Murayama, O.; Park, J.-M.; Sato, S.; Sun, X.; Yamaguchi, H. Lithium inhibits amyloid secretion in COS7 cells transfected with amyloid precursor protein C100. Neuroscience Letters 2002;321 (1-2):61-64.

[21] Chuang, De-Maw; Chen, Ren-wu; Leeds, Peter R.; Qian, Yanning; Wei, Huafeng; Wei, Wenlin beta-Amyloid peptide-induced death of PC 12 cells and cerebellar granule cell neurons is inhibited by long-term lithium treatment. European Journal of Pharmacology 2000;392(3):117-123.

[22] Diaz-Nido, Javier; Alvarez, Gema; Avila, Jesus; Bogonez, Elena; Munoz-Montano, Juan Ramon; Satrustegui, Jorgina Lithium protects cultured neurons against beta-amyloid-induced neurodegeneration. FEBS Letters 1999;453(3):260-264.

[23] Diaz-Nido, Javier; Alvarez, Gema; Avila, Jesus; Bogonez, Elena; Munoz-Montano, Juan Ramon; Satrustegui, Jorgina Lithium protects cultured neurons against beta-amyloid-induced neurodegeneration. FEBS Letters 1999;453 (3):260-264.

[24] Munoz-Montano, J. R.; Moreno, F. J.; Avila, J.; Diaz-Nido, J. Lithium inhibits Alzheimer’s disease-like tau protein phosphorylation in neurons FEBS LETTER. 1997;411(2-3):183-188

[25] Radesater, A.; Peterson, E.; Nilsson, Y.; Luthman, J.; Leonov, S.; Budd, S. L.; Bhat, R. V.; Backstrom, A. Inhibition of GSK3beta by lithium attenuates tau phosphorylation and degeneration. Society for Neuroscience Abstracts 2001;27(1):1437.

[26] Bjorksten J. Pathways to the decisive extension of the human lifespan, J Am Ger Soc 1977;25:396-399

 

 

[1] Moore G J et al. Lithium-induced increase in human brain grey matter. Lancet 2000;356:1241-1242

[1] Chuang, De-Maw; Christ, Lori; Fujimaki, Koichiro; Hashimoto, Ryota; Jeong, Mi Ra Lithium-induced inhibition of Src tyrosine kinase in rat cerebral cortical neurons: A role in neuroprotection against N-methyl-D-aspartate receptor-mediated excitotoxicity. FEBS Letters 2003;538(1-3):45-148.

[1] Hashimoto, R.; Takei, N.; Shimazu, K.; Christ, L.; Lu, B.; Chuang, D. M. Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: an essential step for neuroprotection against glutamate excitotoxicity. Neuropharmacology 2002;43:1173-9

[1] Ren, M.; Kanai, H.; Chuang, D. M.; Chen, R. W.; Chalecka-Franaszek, E.; Qin, Z. H. Regulation of c-Jun n-terminal kinase (JNK) and p38 kinase in cultured brain neurons: Roles of glutamate and lithium. Society for Neuroscience Abstracts 2001;27(1):259.

[1] Chuang, De-Maw Lithium exerts robust neuroprotective effects in vitro and in the CNS in vivo: Therapeutic implications. Neuropsychopharmacology 2000;23(S2):S39.

[1] Nonaka, S.; Hough, C. J.; Chuang, D-M. Chronic lithium treatment robustly protects neurons in the central nervous system against excitotoxicity by inhibiting N-methyl-D-aspartate receptor-mediated calcium influx.Proceedings of the National Academy of Sciences of the United States of America 1998;95(5):2642-2647

[1] Nonaka, S.; Katsube, N.; Chuang, D-M. Lithium protects rat cerebellar granule cells against apoptosis induced by anticonvulsants, phenytoin and carbamazepine. Journal of Pharmacology and Experimental Therapeutics 1998;286(1):539-547

[1] Reda FA, Escobar JJ, Scanlan JM. Lithium Carbonate in the Treatment of tardive dyskinesia. Am J Psych 1975;132(5):560-562

[1] Manji, Husseini K.; Chen, Guang; Moore, Gregory J. Lithium up-regulates the cytoprotective protein Bcl-2 in the CNS in vivo: A role for neurotrophic and neuroprotective effects in manic depressive illness. Journal of Clinical Psychiatry 2000;61(9):82-96.

[1]Manji, Husseini K.; Chen, Guang; Moore, Gregory J. Lithium at 50: Have the neuroprotective effects of this unique cation been overlooked? Biological Psychiatry 1999;46(7): 929-940.

[1] Chuang, D.-M.; Hashimoto, R.; Kanai, H.; Leeds, P.; Senatorov, V. Lithium stimulates progenitor proliferation in cultured brain neurons. Neuroscience 2003;117(1):55-61.

[1] Tsai G, Coyle JT. N-acetyl aspartate in neuropsychiatric disorders. Prog Neurobiol 1995;46:531-540

[1] Moore GJ et al. Lithium Increases N-acetyl aspartate in the human brain: in vivo evidence in support of bcl-2’s neurotrophic effects? Biol Psych 2000;48:1-8

[1] Williams, R. S. B.; Harwood, A. J. Lithium therapy and signal transduction. Trends in Pharmacological Sciences 2000;21(2);61-64

[1] Lenox, Robert H.; Hahn, Chang-Gyu Overview of the mechanism of action of lithium in the brain: Fifty-year update. Journal of Clinical Psychiatry 2000;61 (Supplement 9):5-15.

[1] Williams, R. S. B.; Harwood, A. J. Lithium therapy and signal transduction. Trends in Pharmacological Sciences 2000;21(2);61-64

[1] Lenox, Robert H.; Hahn, Chang-Gyu Overview of the mechanism of action of lithium in the brain: Fifty-year update. Journal of Clinical Psychiatry 2000;61 (Supplement 9):5-15.

[1] Nonaka S, Chuang DM. Neuroprotective effects of chronic lithium on focal cererbral ischemia in rats. Neuroreport 1998;9(9):2081-2084

[1] Weeks, O. I.; Volmar, C. H. Lithium and spatial memory: A new pathway? Society for Neuroscience Abstracts 2001;27 (1) 845.

[1] Takashima, A.; Murayama, M.; Murayama, O.; Park, J.-M.; Sato, S.; Sun, X.; Yamaguchi, H. Lithium inhibits amyloid secretion in COS7 cells transfected with amyloid precursor protein C100. Neuroscience Letters 2002;321 (1-2):61-64.

[1] Chuang, De-Maw; Chen, Ren-wu; Leeds, Peter R.; Qian, Yanning; Wei, Huafeng; Wei, Wenlin beta-Amyloid peptide-induced death of PC 12 cells and cerebellar granule cell neurons is inhibited by long-term lithium treatment. European Journal of Pharmacology 2000;392(3):117-123.

[1] Diaz-Nido, Javier; Alvarez, Gema; Avila, Jesus; Bogonez, Elena; Munoz-Montano, Juan Ramon; Satrustegui, Jorgina Lithium protects cultured neurons against beta-amyloid-induced neurodegeneration. FEBS Letters 1999;453(3):260-264.

[1] Diaz-Nido, Javier; Alvarez, Gema; Avila, Jesus; Bogonez, Elena; Munoz-Montano, Juan Ramon; Satrustegui, Jorgina Lithium protects cultured neurons against beta-amyloid-induced neurodegeneration. FEBS Letters 1999;453 (3):260-264.

[1] Munoz-Montano, J. R.; Moreno, F. J.; Avila, J.; Diaz-Nido, J. Lithium inhibits Alzheimer’s disease-like tau protein phosphorylation in neurons FEBS LETTER. 1997;411(2-3):183-188

[1] Radesater, A.; Peterson, E.; Nilsson, Y.; Luthman, J.; Leonov, S.; Budd, S. L.; Bhat, R. V.; Backstrom, A. Inhibition of GSK3beta by lithium attenuates tau phosphorylation and degeneration. Society for Neuroscience Abstracts 2001;27(1):1437.

[1] Bjorksten J. Pathways to the decisive extension of the human lifespan, J Am Ger Soc 1977;25:396-399