Neuroprotective effects of vitamins C and E against epilepsy-induced neuronal death

Epilepsy,Neuroprotectors — Tags: , , , , — 7:49 am

Epilepsy is thought to be associated with oxidative stress, which play its role in the seizures-induced neuronal death (1, 2). On the other hand, the brain, due to a high content of polyunsaturated fatty acids, is an easy target for the peroxidation. Luckily, it has neuroprotective systems such as superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione (3, 4).

Exogenous antioxidants like vitamin E and C, can inhibit the neuronal damage provoced by lipid peroxidation during seizures and prevent the increase in brain free fatty acid levels, suggesting that the protection may be mediated by, for example, increase of hippocampal catalase activity (5). Vitamin C significantly decreased the lipid peroxidation after seizures induced by cholinergic agonist pilocarpine supporting the idea of interaction of the C and E vitamins with catalase activity to produce neuronal protection amd to decrease the lipid peroxidation level (6).

When oxidative damage accumulates over  years, it may account for the increased incidence of neurodegenerative diseases in aged populations. The mechanisms of neuronal degeneration in these cases remain unknown and this is a major obstacle in the development of effective therapies targeting the causes of the diseases.

Sources

  1. Neurosci Lett 420 (2007), pp. 76–79
  2. Neurosci Lett 291 (2000), pp. 179–182
  3. Cell signaling and neurotoxic events. In: L.W. Chang, Editor, Principles of Neurotoxicology, Marcel Dekker, New York (1994), pp. 475–493
  4. Neurosci Lett 8 (2007), pp. 76–79
  5. Epilepsy Res 46 (2001), pp. 121–128
  6. Pharmac Biochem & Behavior, Volume 89, Issue 1, March 2008, Pages 1-5

Neuroprotective effects of Coenzyme Q10

Neurodegenerative diseases,Neuroprotectors — Tags: , , — 6:00 am

Related: Is Q10 a fitness-enhancing or an anti-aging supplement in the long run?

“Several clinical trials of CoQ10 have been performed in Parkinson’s disease and atypical Parkinson’s syndromes, Huntington’s disease, Alzheimer disease, Friedreich’s ataxia, and amyotrophic lateral sclerosis, with equivocal findings. CoQ10 is widely available in multiple formulations and is very well tolerated with minimal adverse effects, making it an attractive potential therapy.”
Meredith Spindler, M Flint Beal, and Claire Henchcliffe. Coenzyme Q10 effects in neurodegenerative disease. Neuropsychiatr Dis Treat. 2009; 5: 597–610
“There is ample evidence showing involvement of mitochondrial dysfunction in the pathogenesis of neurodegenerative disorders, therefore, one would predict that agents that alleviate mitochondrial dysfunction could be beneficial and exert neuroprotective effects. Several bioenergetic agents that improve mitochondrial function including creatine, coenzyme Q10 (CoQ10), nicotinamide, riboflavin and lipoic acid are being tested for their neuroprotective efficacy in neurodegenerative disorders. Among them, creatine and CoQ10 are in clinical trials for PD, HD and AD.”
Rajnish K. Chaturvedi and M. Flint Beal. Mitochondrial approaches for neuroprotection. Ann N Y Acad Sci. 2008 December; 1147: 395–412
“…combination therapy using CoQ10 and creatine may be useful in the treatment of neurodegenerative diseases such as Parkinson’s disease and HD.”
Lichuan Yang  et al., Combination therapy with Coenzyme Q10 and creatine produces additive neuroprotective effects in models of Parkinson’s and Huntington’s Diseases. J Neurochemistry, 109, 5, 1427–1439, 2009
“…a synthetic analog of CoQ10, idebenone, has been investigated in clinical trials for its ability to inhibit lipid peroxidation. Although several smaller studies reported beneficial effects on memory and attention after several months of treatment, a larger study reported no effect in slowing disease progression.”
Magali Dumont, M. Flint Beal. Neuroprotective strategies involving ROS in Alzheimer disease. Free Radical Biology and Medicine, 2011, online ahead of print
“These data demonstrate that in addition to reducing intracellular deposition of A-beta, CoQ10 can also reduce plaque pathology. Our study further supports the use
of CoQ10 as a therapeutic candidate for AD.”
Xifei Yang et al., Coenzyme Q10 Reduces β-Amyloid Plaque in an APP/PS1
Transgenic Mouse Model of Alzheimer’s Disease. Mol Neurosci (2010) 41:110–113
Abbreviations

PD: Parkinson’s disease;
HD: Huntington’s disease;
AD: Alzheimer’s disease;
A-beta – beta-Amyloid peptide

The eight mechanisms of anti-Alzheimer’s effects of curcumin

Alzheimer's,Neurodegenerative diseases,Neuroprotectors — Tags: , , , — 9:44 am

Related: Resveratrol and curcumin, plant’s own weapons that protect the brain

1. Curcumin is a better antioxidant than alpha-tocopherol and can protect blood vessel cells from oxidative stress caused by Amyloid beta peptide (Abeta), the main constituent of amyloid plaques in the brains of Alzheimer’s disease (AD) patients. Interestingly, with low-dose curcumin, but not with high-dose curcumin the plaque occurrence was decreased by up to 50%.

2. Curcumin significantly lowered levels of oxidized proteins, which content is elevated in the brains of mice model of AD.

3. Curcumin inhibits the formation of fibrillar Abeta (fAbeta) and destabilized already formed fAbeta.

4. In animal models of AD, curcumin prevented cognitive deficits presumably by binding the redox-active metals Fe and Cu.

5. Curcumin decreased Abeta formation. When fed to aged mice with advanced amyloid accumulation, curcumin directly binds small beta-amyloid and blocks fibril formation.

6. Beta-amyloid peptide can form a peroxidase playing a major role in the pathologies of AD. Curcumin inhibits this peroxidase.

7. Curcumin enhances the phagocytosis and Abeta removal by macrophages, the process that is impaired in patients with AD.

8. Curcumin crosses the blood–brain barrier, disrupts existing plaques and partially restores damaged neurones in annimal AD model leading to a significant reversal of structural neuronal damage.

Source

B.B. Aggarwal, K.B. Harikumar. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. The International Journal of Biochemistry & Cell Biology 41 (2009) 40–59

Music is good for the brain

Dementia,Epilepsy,Neuroprotectors,Parkinson's — Tags: , — 11:00 am

The study conducted by researchers at McGill University in Montreal and published in January 2011 issue of Nature Neuroscience showed that the music increased dopamine levels in certain areas of the brain. Various types of music were shown to be effective depending on individual preferences. (1). On the other hand, dopamine is crucial in the brain system of movement organization, deficiencies of brain cells producing dopamine, as we know, result in Parkinson’s disease, and the only reliable method of treatment is the L-DOPA medication having severe side effects and gradually losing its efficiency as the disease progresses.

Other studies revealed that music (e.g., exposure to Mozart’s music) can decrease the blood pressure in hypertensive patients and even experimental animals. Increased dopamine levels improve dopaminergic neurotransmission in epilepsy (2), dementia (3), and ADHD (4).

The beneficial effects of music are thought to work through brain structures involved in reward processing including the nucleus accumbens* and the ventral tegmental area**, hypothalamus*** and insula****

Sources

1. Music – it does a body and mind good, Baxterbulletin.com

2. Brain Res. Rev. 25 (1997), pp. 1–26

3. Exp. Aging Res., Volume 27, Issue 3 July 2001 , pp. 215 – 228

4. J. Learn. Disabil. 29 (1996), pp. 238–246

Footnotes

* also known as “center of motivation”

** a component of the reward pathway in the brain

*** a very important brain area responsible for many bodily functions as well as instincts for basic survival, fight or flight, mating, eating, and drinking, etc.

**** linked to emotions, perception, motor control, self-awareness, cognitive functioning, and interpersonal experience.

MCT and beta-hydroxybutirate protect cognitive and synaptic functions

Energy Homeostasis,Energy Substrates,Glucose,Ketone bodies,Neuroprotectors — 7:57 am


Medium-Chain Fatty Acids Improve Cognitive Function and Support In Vitro Synaptic Transmission During Acute Hypoglycemia (1)

The brain can use alternative fuels such as monocarboxylic acids, lactate, and ketones to maintain energy homeostasis (2-8). Fasting or hypoglycemia causes adaptive changes in the brain, including an enhanced ability to utilize alternative fuels. The work conducted by joined teams from Yale School of Medicine, State University of New York, Winthrop University Hospital, Long Island, Department of Psychology, State University of New York, and University at Albany studied how alternative energy substrates influenced cognitive and synaptic functions disturbed by hypoglycemia.

Impaired verbal memory, digit symbol coding, digit span backwards, and map searching was observed during insulin-induced hypoglycemia. Medium-chain triglycerides given in a drink produced higher free fatty acids and beta-hydroxybutyrate levels and returned cognitive performance to normal levels without adversely affecting adrenergic or symptomatic responses to hypoglycemia.

1. Diabetes 58:1237–1244, 2009
2. Hasselbalch SG, Knudsen GM, Jakobsen J, Hageman LP, Holm S, Paulson
OB. Brain metabolism during short-term starvation in humans. J Cereb
Blood Flow Metab 1994;14:125–131
3. Maran A, Cranston I, Lomas J, Macdonald I, Amiel SA. Protection by
lactate of cerebral function during hypoglycaemia. Lancet 1994;343:16–20
4. Veneman T, Mitrakou A, Mokan M, Cryer P, Gerich J. Effect of hyperketonemia
and hyperlacticacidemia on symptoms, cognitive dysfunction,
and counterregulatory hormone responses during hypoglycemia in normal
humans. Diabetes 1994;43:1311–1317
5. Amiel SA, Archibald HR, Chusney G, Williams AJ, Gale EA. Ketone infusion
lowers hormonal responses to hypoglycaemia: evidence for acute cerebral
utilization of a non-glucose fuel. Clin Sci (Lond) 1991;81:189–194
6. Hawkins RA, Williamson DH, Krebs HA. Ketone-body utilization by adult
and suckling rat brain in vivo. Biochem J 1971;122:13–18
7. Pan JW, Rothman TL, Behar KL, Stein DT, Hetherington HP. Human brain
beta-hydroxybutyrate and lactate increase in fasting-induced ketosis.
J Cereb Blood Flow Metab 2000;20:1502–1507
8. Mason GF, Petersen KF, Lebon V, Rothman DL, Shulman GI. Increased
brain monocarboxylic acid transport and utilization in type 1 diabetes.
Diabetes 2006;55:929–934


Energy substrates and neuroprotection: what does what

Epilepsy,Glucose,Ketone bodies,Lactate,Neuroprotectors,Pyruvate — Tags: — 6:05 am

A few interesting articles about glucose, lactate, and pyruvate
and their neuroprotective functions.

J Neurochem. 2010 Feb 15
Chronic in vitro ketosis is neuroprotective but not anticonvulsant.
Marina Samoilova, Michael Weisspapir, Peter Abdelmalik, Alexander A
Velumian, Peter L Carlen

Chronic in vitro treatment with a ketone body, D-beta-hydroxybutyrate
(DbetaHB), protected the cultures against chronic hypoglycemia,
oxygen-glucose deprivation and NMDA-induced excitotoxicity, but failed
to suppress intrinsic and induced seizure-like activity, indicating
improved neuroprotection is not directly translated into seizure
control. However, chronic in vitro ketosis abolished hippocampal
network hyperexcitability following a metabolic insult, hypoxia,
demonstrating for the first time a direct link between metabolic
resistance and better control of excessive, synchronous, abnormal
electrical activity.

Neuroscience. 2007 Jun 7
Lactate, not pyruvate, is neuronal aerobic glycolysis end product: An
in vitro electrophysiological study. A Schurr, R S Payne

We hypothesized that, in the brain, both aerobic and anaerobic
glycolysis terminate with the formation of lactate from pyruvate by the
enzyme lactate dehydrogenase (LDH). If this hypothesis is correct,
lactate must be the mitochondrial substrate for oxidative energy
metabolism via its oxidation to pyruvate, plausibly by a mitochondrial
LDH

Neurosci Res. 2004 Dec;50 (4):467-74
Glycolysis regulates the induction of lactate utilization for synaptic
potentials after hypoxia in the granule cell of guinea pig hippocampus.
Toshihiro Takata, Bo Yang, Takashi Sakurai, Yasuhiro Okada, Koichi
Yokono

Population spikes are not maintained with lactate following hypoxia in
10 mM glucose medium, but are maintained at their original levels with
lactate after exposure to hypoxia in lower concentration (5 mM) of
glucose.

Neurosci Res. 2003 Jul ;46 (3):333-7
Effects of lactate/pyruvate on synaptic plasticity in the hippocampal
dentate gyrus.
Bo Yang, Takashi Sakurai, Toshihiro Takata, Koichi Yokono

Replacement of glucose with lactate and pyruvate maintained population
spikes after transient depression, and supported a similar degree of
paired-pulse facilitation. These results indicate that monocarboxylates
could serve as sufficient substrates LTP but with less efficiency than
glucose.

Neuroscience. 2007 Jun 7
Lactate, not pyruvate, is neuronal aerobic glycolysis end product: An
in vitro electrophysiological study.A Schurr, R S Payne

 

We hypothesized that, in the brain, both aerobic and anaerobic
glycolysis terminate with the formation of lactate from pyruvate by the
enzyme lactate dehydrogenase (LDH). If this hypothesis is correct,
lactate must be the mitochondrial substrate for oxidative energy
metabolism via its oxidation to pyruvate, plausibly by a mitochondrial
LDH


Neurosci Res. 2004 Dec 50 (4):467-74
Glycolysis regulates the induction of lactate utilization for synaptic
potentials after hypoxia in the granule cell of guinea pig
hippocampus.Toshihiro Takata, Bo Yang, Takashi Sakurai, Yasuhiro Okada,
Koichi Yokono

 

Population spikes are not maintained with lactate following hypoxia in
10 mM glucose medium, but are maintained at their original levels with
lactate after exposure to hypoxia in lower concentration (5 mM) of
glucose.

 

Memory impairment, hippocampal atrophy, and the 10,000 steps a day rule.

Brain metabolism,Dementia,Energy Substrates,Neuroprotectors — 5:34 am

Twenty-five percent of individuals over 65 years of age have sufficient cognitive problems, short of dementia, to affect the quality of their lives (1, 2). The ability to learn consciously and recall new information, which is known as recent or declarative memory, is one of the areas most affected during aging. However, our knowledge about the medical factors that predispose a person to age-associated cognitive problems remains undeveloped.

After the age of 65, a quarter of otherwise normal, healthy people have memory problems serious enough to affect their quality of life. Learning and memorizing new information is the most prominent cognitive deficit in these people. Is there anything that can be done to prevent and/or to improve this condition?

First, it’s important to know what changes in elderly people’s brain and metabolism and how these changes are different in the 25% of those having poorer memories and those that retain robust learning and memory capacity.

  • They have glucose intolerance
  • Their brain region responsible for new memory processing, hippocampus, shrinks according to MRI
  • The delivery of metabolic substrates to the hippocampus is compromised

What can be done?

There are at least two things that should be kept in mind:

1. The 10,000 steps a day does work. In one study, at the background level, participants made average 5,000 steps a day. During the experiment, they were instructed to increase their daily walking (cumulative) to 10,000 steps — and after 4 weeks, not only their glucose tolerance improved, but their blood pressure normalized.

2. Get enough sleep. Reduced sleep duration is associated with glucose intolerance especially when combined with physical inactivity and overeating.

More on brain aging and NDD prevention at Ageless Brain (click to read)

Sources

Unverzagt F et. al., Neurology. 2001;57:1655–1662.

Convit A et. al., Proc Natl Acad Sci USA, 2003, v.100(4); Feb 18

Swartz A et. al., Prev Med. 2003 Oct;37(4):356-62

Nedeltcheva A et al., J Clinical Endocrinology & Metabolism 2009, Vol. 94, No. 9 3242-3250

The MMM of aging: mood, memory, movement

Alzheimer's,Dementia,Neurodegenerative diseases,Neuroprotectors,Parkinson's — Tags: , , , , — 6:55 am

“Thinking, Moving, Feeling”: What Do They Have in Common?

This question opens a review of age-related declines, their inter-relationships, mechanisms, and the ways to postpone if not avoid them. The authors discuss the occurrence of depression and mood disorders during normal, premature or pathological aging, reminding that the usual suspects – serotonin and norepinephrine – indeed decline as people age as well as in Alzheimer’s and Parkinson’s diseases (A, Granholm et al., Mood, Memory and Movement: An Age-Related Neurodegenerative Complex? Curr Aging Sci. 2008 July ; 1(2): 133–139.)

(more…)

The seven effects of ketone bodies making them powerful neuroprotectors

Ketone bodies,Neuroprotectors — Tags: , , , — 9:27 am

There are seven traits allowing ketones to serve as neuroprotectors during brain damage:

  1. they require only three steps to enter the Krebs cycle (footnote a) – compare with 9 steps obligatory for glucose;
  2. they cause  inhibition of glycolysis, thus decreasing free radical formation;
  3. they increase production of ATP (footnote b);
  4. they increase mitochondrial energy efficiency;
  5. they increase antioxidant activity of glutathione peroxidase (footnote c);
  6. they spare pyruvate from processing in the Krebs cycle

Source: Journal of Cerebral Blood Flow & Metabolism (2008) 28, 1–16

Footnotes
a) The Krebs cycle or the citric acid cycle is a metabolic pathway involved in the conversion (“burning”) of carbohydrates, fats and proteins into CO2 and H2O to generate energy in the form that can be used by living organisms.
b) ATP: Adenosine Triphosphate, the ultimate “energy molecule”.
c) Glutathione peroxidase: a powerful scavenger of free radicals.

Both hypervitaminosis D3 and hypovitaminosis D3 cause premature aging of CNS

Brain metabolism,Neuroprotectors,Parkinson's — Tags: , , , , , , , , , , — 7:37 am
Both hypervitaminosis D3 and hypovitaminosis D3 cause premature aging
Vitamin D3 is not a vitamin because it is not biologically active as it is. However, without it, the body’s hormonal system cant function properly without the vitamin, which is not produced by the body so the body has to be helped with proper diet and sun light. The tree hormones are called calcipherols and they are fully dependent on Vit. D3, they  are: calcidiol, calcitriol and 24-calcitriol. The brain is capable of synthesizing the calcipherol hormones and has Vitamin D3 receptors in the cortex, cerebellum, mesopontine area, diencephalon, spinal cord, amygdala, hypothalamus and hippocampus.
Calcipherol hormones are involved in the control of anxiety, autism, seasonal affective disorder, schizophrenia, Parkinson’s and Alzheimer’s diseases, and reducing risk of multiple sclerosis. Hypovitaminosis D3 may cause a premature aging of cognitive functions.
As people age, their calcipherol endocrine system becomes vulnerable. The production of calcipherols by the skin decreases partly because elderly people are less exposed to sunlight. Somewhat of a paradox,, the calcipherol hormone seems to enhance aging. The appearance of prematurely aging mice with hypovitaminosis are similar to those of hypervitaminosis D3. However, the precise role of calcipherol hormones in the brain aging remains to be studied.
Source: Psychoneuroendocrinology (2009) 34S, S278—S286

Related post: Vitamin D and mental health – an easy solution for serious problems?

Vitamin D3 is not a vitamin because it is not biologically active as it is. However, the body’s hormonal system cannot function properly without it since the body has to be helped with proper diet and sun light. The tree hormones are called calcipherols and they are fully dependent on Vit. D3, they  are: calcidiol, calcitriol and 24-calcitriol. The brain is capable of synthesizing the calcipherol hormones and has Vitamin D3 receptors in the cortex, cerebellum, mesopontine area, diencephalon, spinal cord, amygdala, hypothalamus and hippocampus.

Calcipherol hormones are involved in the control of anxiety, autism, seasonal affective disorder, schizophrenia, Parkinson’s and Alzheimer’s diseases, and reducing risk of multiple sclerosis. Hypovitaminosis D3 may cause a premature aging of cognitive functions.

As people age, their calcipherol endocrine system becomes vulnerable. The production of calcipherols by the skin decreases partly because elderly people are less exposed to sunlight. Somewhat of a paradox,, the calcipherol hormone seems to enhance aging. The appearance of prematurely aging mice with hypovitaminosis are similar to those of hypervitaminosis D3. However, the precise role of calcipherol hormones in the brain aging remains to be studied.

Source: Psychoneuroendocrinology (2009) 34S, S278—S286

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