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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 11 of 11. This is the beginning of the thread.
Posted by raybakes on November 18, 2004, at 6:48:42
Article on neuron energy needs and what happens when energy falls too low..
DEATH OF A NEURON Several cellular insults, including mutations, toxins, and lack of oxygen, can induce mitochondrial failure, but the end result is the same: too little energy to meet the cell's demands. Most cells store glycogen and can derive some energy from glycolysis, but neurons are particularly susceptible to damage from low levels of ATP, owing to their high energy needs and almost exclusive reliance on mitochondria for energy.
ATP-driven ion pumps maintain neurons in a low-calcium state; the resulting calcium gradient is essential for the calcium signaling that plays such an important role in neuronal function.3 When calcium enters the cell, the mitochondria act as temporary reservoirs until the ion pumps can lower intracellular calcium to their usual levels. Without sufficient ATP to drive the pumps, however, mitochondrial calcium levels become excessive,4 further impairing the mitochondria and leading to intracellular accumulation of ROS. "Mitochondria cannot work in a high calcium environment," Nicholls explains.
ATP also functions in sequestering neurotransmitters such as glutamate in synaptic vesicles. When the neuron receives an impulse, these vesicles release glutamate into the synapse, where it triggers a calcium influx. The cell then quickly takes up the glutamate, thus removing the stimulation from the synapse and allowing neuronal calcium levels to normalize. But in a low-ATP state, glutamate remains in the synapse indefinitely, which exacerbates already-elevated calcium levels, increases ROS levels, and further impairs the mitochondrion.5
Eventually the calcium overload and excess ROS kill the cell. Tim Greenamyre, professor of neurology and pharmacology at Emory University, says that whether the cell dies by apoptosis or necrosis depends on how quick and severe the damage is. "It's like most insults. If you slam it they die from necrosis," he says. "If you don't, they get their affairs in order and commit suicide."
THE WEAKEST LINK When mutations severely impair mitochondrial proteins, the resulting diseases appear early and impact almost every cell type. That is not the case, however, with milder mutations. "It's a threshold process," Dykens explains. "As long as there is minimal energy [from ATP] then the person may be impaired but not ill." In these cases, he says, the disease may not appear until later in life, as in Parkinson and Alzheimer diseases. "In one cell or another, mitochondrial capacity can't keep pace with demand," he says, and disease results.
Posted by linkadge on November 18, 2004, at 11:05:12
In reply to Brain energy and brain disease, posted by raybakes on November 18, 2004, at 6:48:42
So should we work to prevent glutamate toxicity, or, work to keep cellular energy at a optimal level, or both ??
I certainly don't think that antidepressants do much to solve these types of problems, save for perhaps lesseneing the release of cortisol and preventing dammage this way.
Linkadge
Posted by raybakes on November 18, 2004, at 13:35:55
In reply to Re: Brain energy and brain disease, posted by linkadge on November 18, 2004, at 11:05:12
> So should we work to prevent glutamate toxicity, or, work to keep cellular energy at a optimal level, or both ??
>
> I certainly don't think that antidepressants do much to solve these types of problems, save for perhaps lesseneing the release of cortisol and preventing dammage this way.
>
>
> LinkadgeDefinitely think mitochondrial dysfunction is the primary problem in a lot of cases - interesting that steroids like cortisol are partly synthesised in the mitochondria too. Calcium metabolism affects so many areas as well. I think people expect instant results with antidepressants but really a lot of time and effort needs to go into protecting the brain alongside the medication - seems sensible to prepare the terrain before sowing seeds!
Ray
Posted by linkadge on November 18, 2004, at 15:43:04
In reply to Re: Brain energy and brain disease » linkadge, posted by raybakes on November 18, 2004, at 13:35:55
I think this is right.
Have you read the article...
http://www.mcmanweb.com/article-191.htm
A lot of what you're talking about.
Linkadge
Posted by raybakes on November 18, 2004, at 18:26:53
In reply to Re: Brain energy and brain disease, posted by linkadge on November 18, 2004, at 15:43:04
> I think this is right.
>
> Have you read the article...
>
> http://www.mcmanweb.com/article-191.htm
>
>
> A lot of what you're talking about.
Thanks, that was an interesting article...heard of BDNF before, seems to be associated with certain carbohydrates too..(galectin 1)'Galectin-1 induces astrocyte differentiation, which leads to production of brain-derived neurotrophic factor'
http://glycob.oupjournals.org/cgi/content/abstract/14/4/357
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7673482&dopt=Abstract
Wonder whether saccharides can help with neuronal repair?
Ray
Posted by linkadge on November 18, 2004, at 19:22:49
In reply to Re: Brain energy and brain disease » linkadge, posted by raybakes on November 18, 2004, at 18:26:53
Have I heard of BDNF ???
I am the king of BDNF research.
I have spent the last year researching any possible supplement/drug/etc that has any effect on the expression of BDNF.
BDNF (brain derived neurotrophic factor) and NGF (nerve growth factor) are two of the foremost growth factors in the brain. Most effective antidepressants increase BDNF. BDNF, and NGF contribute to neuronal differentiation and synaptic repair. I wached a real time video of neurons exposed to the BDNF molecule. THe nerves were just sitting around doing nothing, but when BDNF reached them they started branching out and making connections like crazy (good/bad, who knows)
ECT seems to cause the most acute and robust increase in BDNF (like 150% increase). Exercise and AD medications increase it too, but to lesser extends. (30% )
I found an article today that even suggested that mice exposed to Mozart, had higher levels of BDNF and CREB, compared to mice that listened to white noice.
I base my life on the idea that boosting BDNF, kickstarts hippocampal repair.
Linkadge
Posted by raybakes on November 19, 2004, at 15:31:15
In reply to Re: Brain energy and brain disease, posted by linkadge on November 18, 2004, at 19:22:49
Not sure about the galactose - in large amounts it seems to inhibit BDNF..
Ray
Posted by linkadge on November 20, 2004, at 11:19:41
In reply to Re: Brain energy and brain disease » linkadge, posted by raybakes on November 19, 2004, at 15:31:15
galactose ? it that found in certain foods ??
Linkadge
Posted by raybakes on November 20, 2004, at 13:08:38
In reply to Re: Brain energy and brain disease, posted by linkadge on November 20, 2004, at 11:19:41
> galactose ? it that found in certain foods ??
>
>
> LinkadgeIt is, especially in dairy, (part of the disaccharide lactose) but galactose appears to cause problems in excess - just was interested in how it worked with BDNF. Also interested in other saccharides and how they interact with the brain structure and regulation neurotransmitters..
'we find that galectin-1, a member of the family of -galactoside binding proteins, induces astrocyte differentiation, and then the differentiated astrocytes greatly enhance their production of brain-derived neurotrophic factor (BDNF). Induction of astrocyte differentiation and BDNF production by an endogenous mammalian lectin may be a new mechanism for preventing neuronal loss after injury.'
and another saccharide sialic acid is involved in sensitizing neurons to BDNF.
'PSA-NCAM modulates BDNF-dependent survival and differentiation of cortical neurons.'
Department of Morphology, University of Geneva Medical School, 1 rue Michel Servet, CH-1211 Geneva 4, Switzerland.
We show that the loss or inactivation of the polysialic acid (PSA) tail of neural cell adhesion molecule (NCAM) on rat cortical neurons in culture leads to reduced differentiation and survival. The mechanism by which this negative effect is mediated appears to involve the neuronal response to brain-derived neurotrophic factor (BDNF): (i) in the absence of PSA or in the presence of excess free PSA added to the culture medium, BDNF-induced cell signalling is reduced; (ii) the addition of exogenous BDNF to the medium reverses the effect of PSA loss or inactivation. These data suggest that PSA-NCAM, previously shown to modulate cell migration and plasticity, is needed for an adequate sensitivity of neurons to BDNF.
Ray
Posted by linkadge on November 20, 2004, at 15:40:56
In reply to Re: Brain energy and brain disease » linkadge, posted by raybakes on November 20, 2004, at 13:08:38
Sorry, you'll have to cut to the chase for me,
Eat dairy or don't eat dairy?
Linkadge
Posted by raybakes on November 22, 2004, at 11:01:55
In reply to Re: Brain energy and brain disease, posted by linkadge on November 20, 2004, at 15:40:56
> Sorry, you'll have to cut to the chase for me,
>
> Eat dairy or don't eat dairy?
>
>
> LinkadgeSorry, can't really cut to the chase, but this article on glyconutrients and how they affect the brain might explain some of what I was thinking.
http://cms.psychologytoday.com/articles/pto-20040608-000001.html
Ray
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