Low-dose lithium uptake promotes longevity in humans and metazoans.
rs1...@yahoo.com
Low-dose lithium uptake promotes longevity in humans and metazoans.
Zarse K, Terao T, Tian J, Iwata N, Ishii N, Ristow M.
Department of Human Nutrition, Institute of Nutrition, University of
Jena, D-07743, Jena, Germany.
PURPOSE: Lithium is a nutritionally essential trace element
predominantly contained in vegetables, plant-derived foods, and
drinking water. Environmental lithium exposure and concurrent
nutritional intake vary considerably in different regions. We here
have analyzed the possibility that low-dose lithium exposure may
affect mortality in both metazoans and mammals.
METHODS: Based on a large Japanese observational cohort, we have used
weighted regression analysis to identify putative effects of tap water-
derived lithium uptake on overall mortality. Independently, we have
exposed Caenorhabditis elegans, a small roundworm commonly used for
anti-aging studies, to comparable concentrations of lithium, and have
quantified mortality during this intervention.
RESULTS: In humans, we find here an inverse correlation between
drinking water lithium concentrations and all-cause mortality in 18
neighboring Japanese municipalities with a total of 1,206,174
individuals (β = -0.661, p = 0.003). Consistently, we find that
exposure to a comparably low concentration of lithium chloride extends
life span of C. elegans (p = 0.047).
CONCLUSIONS: Taken together, these findings indicate that long-term
low-dose exposure to lithium may exert anti-aging capabilities and
unambiguously decreases mortality in evolutionary distinct species.
PMID: 21301855 [PubMed - as supplied by publisher]
Taka
Chronic lithium downregulates cyclooxygenase-2 activity and
prostaglandin E2 concentration in rat brain
F Bosettia, J Rintalaa, R Seemann, T A Rosenberger, M A Contreras, S I
Rapoport and M C Chang
Brain Physiology and Metabolism Section, National Institute on Aging,
National Institutes of Health, Bethesda, Maryland, USA
Rats treated with lithium chloride for 6 weeks have been reported to
demonstrate reduced turnover of arachidonic acid (AA) in brain
phospholipids, and decreases in mRNA and protein levels, and enzyme
activity, of AA-selective cytosolic phospholipase A2(cPLA2). We now
report that chronic lithium administration to rats significantly
reduced the brain protein level and enzyme activity of
cyclooxygenase-2 (COX-2), without affecting COX-2 mRNA. Lithium also
reduced the brain concentration of prostaglandin E2 (PGE2), a
bioactive product of AA formed via the COX reaction. COX-1 and the
Ca2+-independent iPLA2 (type VI) were unaffected by lithium. These and
prior results indicate that lithium targets a part of the AA cascade
that involves cPLA2 and COX-2. This effect may contribute to lithium's
therapeutic action in bipolar disorder.
Lithium May Come to the Rescue When Brain Is Inflamed
Lithium treatment subdues an inflammatory compound and increases an
anti-inflammatory compound in the brains of animals. Such actions may
help explain why it stabilizes moods in bipolar patients.
Although it has been 40 years since lithium carbonate was approved by
the Food and Drug Administration to treat bipolar disorder, exactly
how it works has not been clear. A common belief, however, is that it
reduces brain inflammation during the manic phase. Indeed, postmortem
frontal cortex samples from individuals with bipolar disorder have
shown signs of inflammation.
And now another study bolstering the hypothesis that lithium counters
bipolar disorder by countering inflammation has been published in the
May Journal of Lipid Research.
The study found that when lithium reaches the brain, it both reduces
levels of the inflammatory compound arachidonic acid and increases
levels of the anti-inflammatory compound 17-OH-DHA, which is formed
from an omega-3 fatty acid—docosahexaenoic acid.
Mireille Basselin, Ph.D., a scientist at the National Institute on
Aging, and colleagues fed 17 rats lithium chloride for six weeks to
produce brain concentrations of lithium that were therapeutically
similar to those obtained in patients taking lithium carbonate. They
fed 17 other rats a lithium-free diet during the six-week period.
During a six-day period, bacterial lipolysaccharide was infused via
cannulas into the brains of both groups of rats to produce an
inflammatory response. The rats were then sacrificed, and findings
from the brains of the two groups were compared.
The group that had not received lithium had a substantial amount of
the inflammatory compound arachidonic acid in their brains, whereas
the group that had received lithium did not. In contrast, the group
that had received lithium had a substantial amount of the anti-
inflammatory compound 17-OH-DHA in their brains, which was not the
case for the lithium-free rats.
So it looks as if lithium can reduce levels of the inflammatory
compound arachidonic acid and increase levels of the anti-inflammatory
compound 17-OH-DHA in the brain. Such actions may explain how lithium
helps people with bipolar disorder, the researchers believe.
Moreover, aspirin, like lithium, is known to increase levels of 17-OH-
DHA, Basselin told Psychiatric News. So these findings may also
explain why researchers recently reported that bipolar subjects who
took aspirin plus lithium did even better than those taking lithium
alone.
Lithium has also been reported to show some therapeutic benefit in
other brain illnesses besides bipolar disorder, Basselin and her
colleagues noted, including Alzheimer's disease, amyotrophic lateral
sclerosis, and HIV-related dementia. These illnesses, like bipolar
disorder, are known to involve brain inflammation. Thus lithium's
therapeutic effectiveness against these illnesses may be due to its
anti-inflammatory actions, Basselin and her team speculated.
SOURCE: http://pn.psychiatryonline.org/content/45/14/13.2.full
SEE ALSO: http://www.psychiatry.wustl.edu/Resources/LiteratureList/2002/August/Rapoport.PDF
--------------------------
Wouldn't it be just easier to get rid of the arachidonic acid .....
Taka
Kofi
<c78a0fe0-da11-4da5...@s29g2000pra.googlegroups.com>,
Taka <taka...@gmail.com> wrote:
>
> Chronic lithium downregulates cyclooxygenase-2 activity and
> prostaglandin E2 concentration in rat brain
>
Effects depend on the tissue type.
lithium causes polyuria in the kidneys by decreasing GSK-3b and
increasing COX-2 and PGE2 [PMID 15585669]
I seem to recall lithium behaving like some sort of PGE1 analogue, but I
can't find the reference.
Alonzo
> In article
> <c78a0fe0-da11-4da5-93f5-f49349040...@s29g2000pra.googlegroups.com>,
>
> Taka <taka0...@gmail.com> wrote:
>
> > Chronic lithium downregulates cyclooxygenase-2 activity and
> > prostaglandin E2 concentration in rat brain
>
> Effects depend on the tissue type.
>
> lithium causes polyuria in the kidneys by decreasing GSK-3b and
> increasing COX-2 and PGE2 [PMID 15585669]
>
> I seem to recall lithium behaving like some sort of PGE1 analogue, but I
> can't find the reference.
Here is some reference to their synergistic effect on neuroprotection:
http://www.nature.com/aps/journal/vaop/ncurrent/abs/aps2010211a.html
Combined prostaglandin E1 and lithium exert potent neuroprotection in
a rat model of cerebral ischemia
Aim: To examine the effects of a mixed formulation composed of
prostaglandin E1 and lithium (PGE1+Li mixture) on brain damage after
cerebral ischemia. The effects of the mixture on protein expression of
heat shock proteins (HSPs), p53, and Bcl-2 were also determined.
Methods: Brain ischemia was induced with a permanent middle cerebral
artery occlusion (pMCAO) in rats. Rats were treated with a single
intravenous administration of PGE1, lithium or a PGE1+Li mixture
immediately after the ischemic insult. The infarct volume and motor
behavior deficits were analyzed 24 h after the ischemic insult. The
protein levels of HSP70, glucose-regulated protein 78 (GRP78), HSP60,
Bcl-2, and p53 in the striatum of the ipsilateral hemisphere were
examined using immunoblotting.
Results: The mixture (PGE1 22.6 nmol/kg+Li 0.5 mmol/kg) reduced
infarct volume and neurological deficits induced by focal cerebral
ischemia. Moreover, the mixture had a greater neuroprotective effect
against cerebral ischemia compared with PGE1 or lithium alone. The
mixture was effective even if it was administered 3 h after ischemia.
PGE1+Li also significantly upregulated cytoprotective HSP70, GRP78,
HSP60, and Bcl-2 protein levels, while decreasing p53 expression.
Conclusion: These results demonstrated a PGE1+Li mixture with a
therapeutic window of up to 3 h for clinical treatment of cerebral
ischemia. The PGE1+Li mixture potentially exerts a protective effect
after stroke through the induction of HSPs and Bcl-2 proteins.
Jason
<29ef599a-2818-4e8e...@x11g2000yqc.googlegroups.com>,
Alonzo <jackson...@googlemail.com> wrote:
Lithium can damage the kidneys.