Longvida Curcumin

Longvida Curcumin is one of my favorite supplements that Jett takes (as well as the whole family). I saw positive results in Jett very quickly -- in fact, at 8 months old, he said his first meaningful word: "water," four days after starting LC! 

Other parents have also reported significant improvements in verbal communication as well as muscle memory. The benefits involve much, much more that you can't see...

You can give it as a supplement or through "golden milk." Jett's brother, Oliver loves it. It's just organic coconut milk (I empty the can into a glass jar, add a little coconut water or water and shake until I get the consistency I want), organic tumeric, a bit of ginger (I used ginger juice), coconut oil or ghee and warm it up. It's really tasty and the mixture works well to deliver the brain-healing powers of whole tumeric instead of just the curcumin. I supplement Oliver with the curcumin as well.

What is curcumin?

Curcumin is a traditional healing herb used in India and other asian countries. Modern research has verified the medicinal value of curcumin, including uses as a potent anti-cancer, anti-inflammatory and brain longevity nutrient. Keep in mind that those with DS have higher levels of amyloid plaques, inflammation, diabetes and negative symptoms related to high metal levels than the typical population.

From Memory Action:
 

• Anti-Inflammatory. In the brain, inflammation is suspected to cause many neuro pathologies, including Alzheimer’s disease. Curcumin significantly inhibited pro-inflammatory substances generated by the immune cells. For example, in Alzheimer’s disease, the formation of amyloid plaques (characteristic of the disease) stimulates an over activation of the immune cells, creating a chronic state of inflammation. This continuous state of inflammation will eventually cause the death of neurons in the brain.
• Reduces Amyloid Plaques. In Alzheimer mice models, curcumin administration enabled the dispersal and clearing of amyloid plaques. There was also a partial restoration of dendrites which were damaged by the plaques.
• Prevention and Reduction of Diabetic Cognitive Decline. The diabetic condition brings about many changes in the brain which result in decreased levels of cognition. Curcumin, in research with diabetic rats, significantly reversed mental declines. Curcumin improved the acetylcholine levels (by reversing increases in acetycholinesterase – the enzyme which breaks down acetylcholine), reduced oxidative stress and inflammation.
• Attenuates damage to the blood-brain-barrier and brain after a stroke. The neuroprotective ability of curcumin extends to that of being protective against damage resulting from cerebral ischemia (i.e. a stroke). In research studies, the area of ischemia damage to the brain was significantly reduced, due to curcumin protecting the blood-brain-barrier.
• Protects against memory loss due to heavy metal toxicity. Lab animals fed curcumin in conjunction with the heavy metal lead, experienced less memory impairment than those not taking curcumin.
• Promotes neurogenesis by increasing serotonin and BDNF (brain derived neurotrophic factor). 
• Supports the Cardiovascular System
  
  Diminishes cardiotoxicity from Adriamycin (a chemotherapeutic drug) and supporting a healthy heart in diabetic patients. Curcumin’s anti-thrombotic (anti-clotting), anti-inflammatory and anti-proliferative effects may also protect the health of the arteries and heart. Other effects include lessening the development of cardiac hypertrophy (enlargement) and heart failure in animals, and supporting healthy atrial and ventricular heart rhythm.
  Through other avenues of effect, curcumin may preserve heart muscle function after ischemic (lack of oxygen) or biochemical damage to the heart. Also, curcumin decreases the extent of cardiovascular remodeling in experimental models of pressure overload (when the pressure from the circulation is excessive on the heart it damages the muscle). From: Beyond Brain Health by Chris D. Meletis, ND

Where to Purchase Products, see DS Day to Day Store

In the UK, you can purchase it online at:
Amazon.com
Special Health Store
or the cream at Mandi Mart

In the US:
Phytosenia ($44.99 plus $12 shipping to US) But, through their program as a distributor, you get the curcumin for $28 per bottle. Only catch...you have to order 6 at a time. Since you may already be spending at least $35 per bottle, it’s at if you’re ordering 4 and getting 2 free. Get with someone else who lives nearby if you can and split the order. Or work it out with someone that you could split the order – one of you orders and sends half to the other person. (If you are in the southeast Wisconsin area, let me know so we can go in together!)

It's easy to fill out the application & be accepted. You might reference the fact that you have a special needs individual at home and that’s what it’s for. Or you could just become a real distributor, which means selling it for the MSRP of $35.

The 30,000 mg bulk powder is 44.99, 6+ is 28.11 each, 25+ is 27.35, 100+ is 26.59 1 kg bulk powder is 635.00, 6+ is 575 each (big savings) Capsules 44.99, 6+ is 27.51, 25+ is 26.10, 100+ is 25.40 Shipping varies from 12.95 to 35.00. All wholesale accounts have same pricing.

Prohealth.com  $39.56 including shipping (When you sign up for autoship/billing. This is one of the few products that I feel is worth autoship/billing!)

Nutrivene $34 plus $8 in shipping ($42) (They also sell TriEnza enzymes)

Vitamin Research Products. For 2 bottles, including shipping, it's $66.90, ($33.45 each) when they have a 50% off sale.

Another possible product: Some on the autism lists are claiming that Enhansa is very effective also. http://www.leesilsby.com/enhansamain.php I don't know how the price compares or efficacy.

For the Longvida Curcumin, 2000 mgs/day is the minimum dose adults have seen results at, but you want to eventually work your way up to 4000 mgs/day.

I saw results with Jett by 4 days at the 1st amount!

What are the possible side effects?

If your child gets irritable, too hyper or has diarrhea, reduce the dose and add in TriEnza enzymes to break down the phenols. Make sure your child drinks more water once you've introduced curcumin. It makes Jett very thirsty and constipated if he's not drinking enough water with it. In fact, at 8 months old, he said his first meaningful word: "water," four days after starting LC because he was so thirsty.

How can I give it?

LC has a very mild flavor. I've had no problems with Jett taking it mixed in applesauce, mashed cauliflower, yogurt or soft scrambled eggs.

Suggested Introduction Schedule

According to http://www.riverbendds.org/longvidadose.html, Dr. Leichtman and INI recommend not starting Longvida curcumin until one year of age due to "diet issues," which I'm assuming means difficulty in digestion. I do know that countries around the world have curcumin in infant formula. (I don't know how much or what form.) Again, I started Jett at 8 months.

Week 1 - 1/4 teaspoon (500 mg) in the morning.

Week 2 - 1/4 teaspoon (500 mg) in the morning. And 1/8 teaspoon (250 mg) no closer than four hours before bedtime. If it keeps him up at night or thrashing too much, change the time to 1/2 hour earlier the next night until you find a good time to give it.

Week 3 - 1/4 teaspoon (500 mg) in the morning. And 1/4 teaspoon (500 mg) closest to bedtime w/out disturbing sleep.

Week 4- in the morning. And 1/4 teaspoon (500 mg) at night.

Week 5 & 6- 1/2 teaspoon (1000 mg) in the morning. And 1/2 teaspoon (1000 mg) at night. Stay at 1 tsp for a while (a month) and then slowly increase until you get to 4000mg (2tsp) without diarrhea. I only have my son on 1000 mg total so far because any more disturbs his sleep. He only weighs 16 lbs and I will eventually increase his dosage.

Update: Jett weighs 18.2 lbs and is 20 months old. He can now tolerate a scoop and a half with no sleep disturbance.

Update: At 27 lbs, Jett takes two capsules with no problems.

_________ 

Beyond Brain Health

by Chris D. Meletis, ND

  

...Researchers from UCLA have been able to resolve this challenge by increasing the bioavailability of curcumin in a unique form known as Longvida®. As was mentioned in the November issue of Vitamin Research News, in clinical studies, Longvida shows demonstrably increased levels achieved in the blood stream, and perhaps even more important is the ability of this breakthrough form of curcumin to cross the blood-brain barrier.1 (The blood-brain barrier is composed of a specialized layer of cells that restricts the passage of many substances from the general circulation into the brain. It presents a challenge in the treatment of brain conditions as it limits the ability of many therapeutic agents to enter the brain.)

This ability to optimize the absorption of curcumin is important in that curcumin’s benefits are multifactorial, and it may perhaps be one of the most scientifically researched natural compounds as literally thousands of studies investigating its effects have been carried out. This article will serve as a review of some of curcumin’s most promising qualities, several of which will be highlighted below.

  

Neurological Health

Curcumin’s influence on the brain is mainly attributed to its anti-inflammatory and antioxidative effects; however, other mechanisms are apparent as well.3 In animal models of cognitive dysfunction, curcumin administration lowered amyloid beta (Abeta) (the principle component of senile plaques that are the driving pathology in brain disorders) by slowing the production of amyloid-beta precursor protein (APP).4 Curcumin will also bind to the Abeta fibrils and aggregates5 where it may have a direct effect on decreasing amyloid pathology.6 The anti-inflammatory, antioxidant and anti-amyloid activity of curcumin in cognitive health makes it a promising area of research.7

In mood balancing, curcumin is thought to have potential clinical usefulness because of its ability to 1) Inhibit monoamine oxidase and thereby enhance the release of serotonin and dopamine and 2) Enhance neurogenesis, namely in the frontal cortex and hippocampus.8-9 Several animal studies highlight the benefits of curcumin in improving mood; curcumin boosted monoamine oxidase inhibition, enhanced serotonin and dopamine levels and reversed stress-related behaviors.10-12 Additional animal studies show a protective effect of curcumin against seizures as well; the neuroprotective and antioxidative effects are thought to be responsible.13-15

  

Anti-Inflammatory Effects

Inflammation is widely used as a term to loosely define pathological immunologic effects. Overexpression of inflammatory pathways is undoubtedly associated with many disease processes. Curcumin exhibits a number of anti-inflammatory effects, and it has been studied in lung health and immune challenges. Controlling inflammation occurs at numerous levels; a number of studies have elucidated key areas where curcumin has an effective role in thwarting specific inflammatory processes thereby resulting in positive clinical outcomes.

  

Lung Health

In asthmatic mouse models, curcumin decreased the total number of leukocytes (white blood cells, a component of inflammation) and eosinophils (additional allergy-mediating cells) in lung fluid. Additionally, other inflammatory cells and mucus occlusion in lung tissues were decreased as well as IgE (a primary immunological mediator of allergy) in the lung fluid. Investigators of this study conclude that curcumin produced these positive effects through inhibition of NF-kappaB.16

Curcumin’s potent anti-inflammatory effects stem from its ability to modulate T and B cells, macrophages, neutrophils, dendritic and natural killer cells. It also down regulates the expression of pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukins 1, 2, 6, 7 and 12, and NF-kappaB as previously mentioned.17

Curcumin is a direct free radical scavenger in the lung tissue (and elsewhere), and can down regulate other pro-inflammatory mediators including matrix metalloproteinase, adhesion molecules and growth factor receptor genes, thereby exerting antioxidative and anti-inflammatory effects in the lungs.18

As an adjunctive therapy to standard corticosteroid treatment in asthma and chronic obstructive pulmonary disease (COPD), curcumin shows promise as well. Histone deacetylase 2 (HDAC-2) is an enzyme that plays a major role in how corticosteroids work; its function is decreased in circumstances of steroid insensitivity, and oxidative stress further compromises its function. Curcumin improves HDAC activity and thereby restores corticosteroid function.19

  

Joint Function

Curcumin also shows benefit in joint health. Animals with arthritis who were given curcumin experienced a dose-related suppression in arthritic signs and symptoms; markers such as infiltration of immune cells, synovial hyperplasia (thickening of inner joint tissue), destruction of cartilage and bone erosion were all halted by curcumin.20 Additionally, matrix metalloproteinases 1 and 3 (MMP-1, MMP-3) and tumor necrosis factor-alpha (TNF-alpha)-stimulated chondrocytes and fibroblasts (diseased joint cells) were also inhibited by curcumin in a dose dependent manner.

Furthermore, in an animal model of osteoarthritis, curcumin significantly decreased interleukin-1beta stimulated release of glycosaminoglycans (GAGS) with increasing doses to pre-experimental levels.21 In a similarly designed study using human chondrocytes (cartilage cells found in joints), curcumin inhibited several inflammatory markers including nitric oxide, prostaglandin E2, interleukins 6 and 8 and MMP-3 all in direct relationship to the dose used.22 Curcumin’s potent anti-inflammatory effects on chondrocytes support its use in joint health.

  

Specific Organ Health

Curcumin and its metabolites offer protection for a variety of conditions and organ systems. At the root of curcumin’s efficacy in these areas are its anti-inflammatory and antioxidative effects, as previously discussed. The following are a few brief areas where curcumin research has provided some valuable insight into its protective effects.

  

Kidney and Liver

Tetrahydrocurcumin (THU1) is one of curcumin’s major metabolites and shows some of the highest antioxidative activity. THU1 has been shown to improve 2 major kidney functions, creatinine and urea clearance; it is also supportive in kidney health after kidney transplants. In the liver, previous studies have shown reduced liver damage from iron, aflatoxin- and benzo[a]pyrene- induced mutagenicity.23

  

Cardiovascular System

The effects of curcumin have been widely researched in the cardiovascular system. Benefits of curcumin here include diminished cardiotoxicity from Adriamycin (a chemotherapeutic drug) and supporting a healthy heart in diabetic patients. Curcumin’s anti-thrombotic (anti-clotting), anti-inflammatory and anti-proliferative effects may also protect the health of the arteries and heart. Other effects include lessening the development of cardiac hypertrophy (enlargement) and heart failure in animals, and supporting healthy atrial and ventricular heart rhythm.24

Through other avenues of effect, curcumin may preserve heart muscle function after ischemic (lack of oxygen) or biochemical damage to the heart. Also, curcumin decreases the extent of cardiovascular remodeling in experimental models of pressure overload (when the pressure from the circulation is excessive on the heart it damages the muscle).25

  

Conclusion

The medical literature contains thousands of studies investigating the role of curcumin in health. Curcumin’s health benefits are wide ranging, and this brief review only provides a fraction of the data concerning curcumin. Already an effective agent for health promotion, a newer, highly bioavailable form of the herb called Longvida is now available, thereby increasing our access to curcumin’s benefits. An important aspect of this improved form of curcumin is its ability to enter neurological circulation by crossing the blood-brain barrier. This novel breakthough allows for potentially greater clinical benefits from curcumin.

  

References
1. Frautschy SA et al. Efficacy of curcumin formulations in relation to systemic availability in the brain and different blood compartments in neuroinflammatory and AD models at the 39th Annual Meeting of the Society of Neuroscience, Chicago, October 2009.
2. Srivastava RM, Singh S, Dubey SK, et al. Immunomodulatory and therapeutic activity of curcumin. Int Immunopharmacol. 2010 Sep 8. [Epub ahead of print]
3. Kulkarni SK, Dhir A. An overview of curcumin in neurological disorders. Indian J Pharm Sci. 2010 Mar;72(2):149-54.
4. Zhang C, Browne A, Child D, Tanzi RE. Curcumin decreases amyloid-beta peptide levels by attenuating the maturation of amyloid-beta precursor protein. J Biol Chem. 2010 Sep 10;285(37):28472-80. Epub 2010 Jul 9.
5. Yanagisawa D, Shirai N, Amatsubo T, et al. Relationship between the tautomeric structures of curcumin derivatives and their Abeta-binding activities in the context of therapies for Alzheimer’s disease. Biomaterials. 2010 May;31(14):4179-85.
6. Ringman JM, Frautschy SA, Cole GM, et al. A potential role of the curry spice curcumin in Alzheimer’s disease. Curr Alzheimer Res. 2005 Apr;2(2):131-6.
7. Frautschy SA, Cole GM. Why pleiotropic interventions are needed for Alzheimer’s disease. Mol Neurobiol. 2010 Jun;41(2-3):392-409. Epub 2010 May 2.
8. Kulkarni S, Dhir A, Akula KK. Potentials of curcumin as an antidepressant. ScientificWorld Journal. 2009 Nov 1;9:1233-41.
9. Xu Y, Ku B, Cui L, et al Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats. Brain Res. 2007 Aug 8;1162:9-18. Epub 2007 Jun 21.
10. Bhutani MK, Bishnoi M, Kulkarni SK. Anti-depressant like effect of curcumin and its combination with piperine in unpredictable chronic stress-induced behavioral, biochemical and neurochemical changes. Pharmacol Biochem Behav. 2009 Mar;92(1):39-43. Epub 2008 Oct 25.
11. Wang R, Xu Y, Wu HL, et al. The antidepressant effects of curcumin in the forced swimming test involve 5-HT1 and 5-HT2 receptors. Eur J Pharmacol. 2008 Jan 6;578(1):43-50. Epub 2007 Sep 19.
12. Xu Y, Ku BS, Yao HY, et al. The effects of curcumin on depressive-like behaviors in mice. Eur J Pharma col. 2005 Jul 25;518(1):40-6.
13. Bharal N, Sahaya K, Jain S, et al. Curcumin has anticonvulsant activity on increasing current electroshock seizures in mice. Phytother Res. 2008 Dec;22(12):1660-4.
14. Jyoti A, Sethi P, Sharma D. Curcumin protects against electrobehavioral progression of seizures in the iron-induced experimental model of epileptogenesis. Epilepsy Behav. 2009 Feb;14(2):300-8. Epub 2008 Dec 17.
15. Sumanont Y, Murakami Y, Tohda M, et al. Prevention of kainic acid-induced changes in nitric oxide level and neuronal cell damage in the rat hippocampus by manganese complexes of curcumin and diacetylcurcumin. Life Sci. 2006 Mar 13;78(16):1884-91. Epub 2005 Nov 2.
16. Oh SW, Cha JY, Jung JE, et al. Curcumin attenuates allergic airway inflammation and hyper-responsiveness in mice through NF-kappaB inhibition J Ethnopharmacol. 2010 Jul 17. [Epub ahead of print]
17. Jagetia GC, Aggarwal BB. “Spicing up” of the immune system by curcumin. J Clin Immunol. 2007 Jan;27(1):19-35. Epub 2007 Jan 9.
18. Biswas S, Rahman I. Modulation of steroid activity in chronic inflammation: a novel anti-inflammatory role for curcumin. Mol Nutr Food Res. 2008 Sep;52(9):987-94.
19. Marwick JA, Ito K, Adcock IM, Kirkham PA. Oxidative stress and steroid resistance in asthma and COPD: pharmacological manipulation of HDAC-2 as a therapeutic strategy. Expert Opin Ther Targets. 2007 Jun;11(6):745-55.
20. Mun SH, Kim HS, Kim JW, et al. Oral administration of curcumin suppresses production of matrix metalloproteinase (MMP)-1 and MMP-3 to ameliorate collagen-induced arthritis: inhibition of the PKCdelta/JNK/c-Jun pathway. J Pharmacol Sci. 2009 Sep;111(1):13-21.
21. Clutterbuck AL, Mobasheri A, Shakibaei M, et al. Interleukin-1beta-induced extracellular matrix degradation and glycosaminoglycan release is inhibited by curcumin in an explant model of cartilage inflammation. Ann N Y Acad Sci. 2009 Aug;1171:428-35.
22. Mathy-Hartert M, Jacquemond-Collet I, Priem F, et al. Curcumin inhibits pro-inflammatory mediators and metalloproteinase-3 production by chondrocytes. Inflamm Res. 2009 Dec;58(12):899-908. Epub 2009 Jul 5.
23. Osawa T. Nephroprotective and hepatoprotective effects of curcuminoids. Adv Exp Med Biol. 2007;595:407-23.
24. Wongcharoen W, Phrommintikul A. The protective role of curcumin in cardiovascular diseases. Int J Cardiol. 2009 Apr 3;133(2):145-51. Epub 2009 Feb 23.
25. Srivastava G, Mehta JL. Currying the heart: curcumin and cardioprotection. J Cardiovasc Pharmacol Ther. 2009 Mar;14(1):22-7. Epub 2009 Jan 18.

_____

Teresa Cody's Comments on Curcumin

I finally had a chance to research curcumin and I am delightfully surprised. It has some properties similar to Prozac but it has even more. One research study I found looked at curcumin using what is called an 'unpedictable stress model'. It is when the researchers stess the mice in randam, unpredictable ways. They have found this to be the most stressful. If stress is consistent and/or predictable, it is not as hard on the body or brain.
Curcumin did increase neurogenesis by increasing serotonin and BDNF (brain derived neurotrophic factor). But it did something more that I think may be the biggest help to Down syndrome.
Curcumin is an anti-inflammatory as well as an antioxidant, but that is not the most intriguing part of the research. Lots of herbs and vitamins are anti-inflammatory or have antioxidant properties.
The most intriguing part is the idea that curcumin is structurally capable of binding to amyloid plaques and breaking up the aggregation of them. Curcumin literally sticks itself to the junk (amyloid plaque) and breaks up the group of them stuck together.
This group of junk clogs up the brain and stops it from working.
Down syndrome has a triplicate copy of the APP gene. Amyloid precursor protein gene. This is the gene associated with Alzheimer's disease. In Alzheimer's disease, brain researchers find the brains full of plaques and tangles. The plaques are called amyloid plaques.
Now, the big drawback I see to curcumin is getting it into the brain. It doesn't cross the BBB (blood brain barrier) easily. But, one brand, Longvida Curcumin, came up with an intriguing solution. They combined curcumin with lecithin. What does that do, you ask? Well, lecithin is phosphatidyl choline, a fat that will cross the BBB. Brilliant!!!
I think curcumin is a fantastic addition for the health of the Down syndrome brain (and probably everyone would benefit).

Why Curcumin interferes with sleep

  

Regarding the sleep problem at night with curcumin:

Curcumin is a GSK-3beta inhibitor and GSK-3 is involved with the circadian clock.

Sounds like it is wise to avoid use of GSK-3beta inhibitors at night.

http://www.ncbi.nlm.nih.gov/pubmed/18720192

http://www.ncbi.nlm.nih.gov/pubmed/15972822

Study Abstracts

Acta Pol Pharm,   2011 Sep-Oct;68(5):769-75.
Evaluation of antidepressant like activity of curcumin and its combination with fluoxetine and imipramine: an acute and chronic study.
Sanmukhani J, Anovadiya A, Tripathi CB.

http://www.ncbi.nlm.nih.gov/pubmed/21928724
Department of Pharmacology, Government Medical College, Bhavnagar - 364001, Gujarat, India.


Abstract

Curcumin is the active ingredient of commonly used spice Curuma longa Linn. In the present study, the antidepressant like activity of curcumin and its combination with fluoxetine and imipramine was studied in acute model (three doses 24, 5 and 1 h before test) of forced swimming test (FST) in glass jar and tail suspension test (TST) in mice and in chronic model (14 day study) of FST with water wheel in rats. All the tests were carried out in the following seven groups (n = 6 in each group), drugs being given orally (doses for mice): Group 1 (vehicle), group 2 (curcumin 50 mg/kg), group 3 (curcumin 100 mg/kg), group 4 (fluoxetine 20 mg/kg), group 5 (imipramine 15 mg/kg), group 6 (curcumin 100 mg/kg plus fluoxetine 20 mg/kg) and group 7 (curcumin 100 mg/kg plus imipramine 15 mg/kg). Equivalent doses for rats were used. Both the acute model of FST and TST, and the chronic model of FST with water wheel showed significant antidepressant like activity of curcumin in 100 mg/kg dose as compared to vehicle control (p < 0.05). The effect of curcumin (100 mg/kg) was similar to that of fluoxetine and imipramine (p > 0.05) but its addition to fluoxetine and imipramine did not improve their antidepressant activity (p > 0.05). Curcumin increased both the swimming and climbing behavior in FST, thus its antidepressant like activity could be due to an increase in serotonin, norepinephrine and dopamine levels in the brain. Curcumin can be a useful antidepressant especially in cases which respond to drugs having mixed effects on serotonin and catecholamines levels in the brain.

PMID:21928724[ PubMed - indexed for MEDLINE]


Curcumin prevents corticosterone- induced neurotoxicity and abnormalities of neuroplasticity via 5-HT receptor pathway.

http://www.ncbi.nlm.nih.gov/pubmed/21689105

J Neurochem.2011 Sep;118(5):784- 95.  Epub 2011
Jul 18.
by Xu Y, Li S, Vernon MM, Pan J, Chen L, Barish PA, Zhang Y, Acharya AP, Yu J, Govindarajan SS, Boykin E, Pan X, O'Donnell JM, Ogle WO.

Abstract

Curcumin, a major active component of Curcuma longa, possesses antioxidant and neuroprotective activities. The present study explores the mechanisms underlying the neuroprotective effect of curcumin against corticosterone and its relation to 5-hydroxy tryptamine (5-HT) receptors. Exposure of cortical neurons to corticosterone results in decreased mRNA levels for three 5-HT receptor subtypes, 5-HT(1A), 5-HT(2A) and 5-HT(4), but 5-HT(1B,) 5-HT(2B), 5-HT(2C), 5-HT(6) and 5-HT(7) receptors remain unchanged. Pre-treatment with curcumin reversed this effect on mRNA for the 5-HT(1A) and 5-HT(4) receptors, but not for the 5-HT(2A) receptor. Moreover, curcumin exerted a neuroprotective effect against corticosterone-induced neuronal death. This observed effect of curcumin was partially blocked by either 5-HT(1A) receptor antagonist p-MPPI or 5-HT(4) receptor antagonist RS 39604 alone; whereas, the simultaneous application of both antagonists completely reversed the effect. Curcumin was also found to regulate corticosterone-induced morphological changes such as increases in soma size, dendritic branching and dendritic spine density, as well as elevate synaptophysin expression in cortical neurons. p-MPPI and RS 39604 reversed the effect of curcumin-induced change in neuronal morphology and synaptophysin expression of corticosterone-treated neurons. In addition, an increase in cyclic adenosine monophosphate (cAMP) level was observed after curcumin treatment, which was further prevented by RS 39604, but not by p-MPPI. However, curcumin-induced elevation in protein kinase A activity and phosphorylation of cAMP response element-binding protein levels were inhibited by both p-MPPI and RS 39604. These findings suggest that the neuroprotection and modulation of neuroplasticity exhibited by curcumin might be mediated, at least in part, via the 5-HT receptor-cAMP-PKA-CREB signal pathway.

© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

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