Decreased Brain Glutamate in Alzheimer’s Disease and excitotoxic effect of Glutamate in Parkinson’s disease

Glutamate (Glu) is the most abundant excitatory neurotransmitter in the central nervous system (CNS) and is involved in the pathophysiology of Alzheimer’s disease (AD) in which there is an increased excitotoxicity.

Biochemical composition of living tissues including the levels of Glu was analyzed by magnetic resonance spectroscopy (MRS). Previous reports point to decreased levels of Glu in AD.

As Glu plays an important role in memory, we hypothesize that Glu levels are decreased in patients with AD when compared with controls.
A consecutive sample of 30 patients with mild-to-moderate AD underwent H-MRS with the voxel placed in the bilateral posterior cingulate gyrus.

For comparison purposes, we carried out the same technique in 68 patients with mild cognitive impairment (MCI) and in 26 controls.
The healthy controls had higher metabolite levels of N-acetyl-aspartate (NAA) than patients with MCI and AD.

In turn, patients with MCI and the controls had higher levels of Glu than in patients with AD. The differences were significant in the analysis of variance (ANOVA) test model corrected for age.
In the post hoc analysis, the most remarkable differences were seen between patients with AD and the rest (patients with MCI and the controls). In AD, the levels of Glu and NAA are decreased in comparison with MCI and normality, which reflects loss of neurons.
FAYED, N., MODREGO, P. J., ROJAS-SALINAS, G., AGUILAR, K.
AMERICAN JOURNAL OF ALZHEIMER’S DISEASE AND OTHER DEMENTIAS26(6):450-456, 20111533-3175

Glutamate and Parkinson’s disease (PD)

Altered glutamatergic neurotransmission and neuronal metabolic dysfunction appear to be central to the pathophysiology of Parkinson’s disease (PD).

The substantia nigra pars compacta, the area where the primary pathological lesion is located, is particularly exposed to oxidative stress and toxic and metabolic insults.

A reduced capacity to cope with metabolic demands, possibly related to impaired mitochondrial function, may render nigral highly vulnerable to the effects of glutamate, which acts as a neurotoxin in the presence of impaired cellular energy metabolism.

In this way, glutamate may participate in the pathogenesis of PD. Degeneration of dopamine nigral neurons is followed by striatal dopaminergic denervation, which causes a cascade of functional modifications in the activity of basal ganglia nuclei. As an excitatory neurotransmitter, glutamate plays a pivotal role in normal basal ganglia circuitry.

With nigrostriatal dopaminergic depletion, the glutamatergic projections from subthalamic nucleus to the basal ganglia output nuclei become overactive and there are regulatory changes in glutamate receptors in these regions. There is also evidence of increased glutamatergic activity in the striatum.

In animal models, blockade of glutamate receptors ameliorates the motor manifestations of PD. Therefore, it appears that abnormal patterns of glutamatergic neurotransmission are important in the symptoms of PD. The involvement of the glutamatergic system in the pathogenesis and symptomatology of PD provides potential new targets for therapeutic intervention in this neurodegenerative disorder.

Blandini F, Porter RH, Greenamyre JT. Neurological Institute C. Mondino, University of Pavia, Italy.

About Glutamate (derived glucose) in other diseases

GABA and glutamate are neurotransmitters, chemical messengers in your brain. One is calming, one is stimulating, and they’re supposed to stay in balance with each other. So what happens if this balance is thrown off?

Some research suggests an imbalance of these two substances may play a role in fibromyalgia (FMS). Research is less solid on their involvement in chronic fatigue syndrome (ME/CFS), with some studies turning up evidence of dysregulation and others finding nothing.

In Your Brain
The human brain is incredibly complex. Each neurotransmitter performs a variety of functions, and they interact with each other and your neurons (brain cells) in an intricate manner that we don’t fully understand.

Still, we’re constantly learning more about the brain and researchers have been able to link certain neurotransmitter abnormalities to certain illnesses or symptoms. They’ve also found ways to manipulate neurotransmitter function and see the very real effects it has on research subjects.
The brain is an efficient recycler, often using one neurotransmitter to create another. This function makes a lot of sense when you’re talking about neurotransmitters with opposite functions, such as GABA and glutamate, or the better-known serotonin and melatonin.

Glutamate
A primary function of glutamate is to get brain cells fired up. It stimulates them so they can do important things like learning new information or forming memories – other things in which glutamate is involved.

However, too much of a stimulant isn’t a good thing, as anyone who’s drunk way too much coffee can tell you. Glutamate can become what’s called an “exitotoxin,” meaning that it appears to excite neurons until they die.

Glutamate is believed to be involved in some degenerative brain diseases such as Alzheimer’s disease and amyotrophic lateral sclerosis (ALS or Lou Gherig’s disease.) (Note: FMS and ME/CFS are NOT believed to be degenerative.)
In FMS, research shows abnormally high levels of glutamate in a part of the brain called the insula or insular cortex. Researchers went looking there because that area is highly involved in pain and emotion, which are key components of the condition. The insula is also involved in sensory perception, motor skills, anxiety, eating disorders and addiction.
Research also has linked high glutamate levels with depression and low cognitive function in people with type 1 diabetes. (Glutamate can be derived glucose, which is often high in diabetics.) At least one FMS study has suggested that lowering glutamate levels can reduce pain.

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Connie’s comments: Protect our brain from excitotoxins (radiation and others), metal toxins, metabolic toxins and get nourishment from whole foods.

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