|
Autism
is characterized by a spectrum of behaviors and developmental delays
that are generally attributed to a complex set of neurological
disturbances that result from a combination of genetic and
environmental factors. Many of the alternative treatment approaches
or adjunct therapies for patients with neurodegenerative disorders
are designed to improve methylation and detoxifi cation
pathways.
These treatments
generally view the environment or other external sources, like
mercury in vaccines, as the origin of the neurotoxic substances.
Neurotoxins are defined as chemical substances that are lethal to
neurons. While the environment certainly can be a source of
neurotoxins, these therapeutic protocols overlook the fact that
neurotoxic substances may originate within the body and can actually
be formed within the neurons themselves.
Neurotoxin Synthesis
Neurotransmitters are metabolized in a
two-step process that utilizes the enzymes monoamine oxidase (MAO)
and aldehyde dehydrogenase. The fi rst step involves MAO, which is
present within the cytoplasm of neurons, and breaks down
neurotransmitters to form highly reactive aldehyde intermediates.
The dopamine metabolite DOPAL (3-, 4-dihydroxyphenylethanol) is one
of the reactive aldehyde intermediates formed by MAO and is a potent
neurotoxin.
Studies have found that Parkinson's-like
brain lesions can be induced with DOPAL and that the cognitive
impairment seen has similarities to autism1. MAO is a mitochondrial
enzyme and is present inside the neurons, but not inside the
neurotransmitter vesicles within the neuron. As such, DOPAL and
related reactive neurotransmitter aldehydes are formed from
neurotransmitter pools that are present inside a neuron, but outside
of the intracellular vesicles. Excessive catecholamine (dopamine,
norepinephrine, and epinephrine) neurotransmitter turnover, the sum
of neurotransmitter fi ring and reuptake, increases the production
of these neurotoxins. In order to limit the formation of these
aldehydes, it is necessary to limit the supply of neurotransmitters
present in the cytoplasm.
A common misconception regarding
neurotransmitter turnover and degradation is that neurotransmitter
molecules are only released from the vesicles via synaptic release
and that the neurotransmitters degraded by MAO are only those that
have been returned to the neuron through an active reuptake
mechanism. While it is true that this is one source of
neurotransmitter degradation products, neurotransmitters can also
leak out of vesicles directly. This leaking process is a signifi
cant source of neurotransmitters degraded by MAO and therefore
neurotoxin formation.
In summary, neurotoxic aldehyde formation
comes from two sources:
• reuptake
degradation
• vesicle leakage degradation
In a normal heathy situation, the active
release of neurotransmitters and subsequent reuptake contributes
only a very small fraction <2% of the neurotransmitters
metabolized by MAO to form the neurotoxic reactive aldehydes. The
primary source >98% is the constant non-specifi c leaking of
neurotransmitters directly from the vesicles. This situation changes
dramatically when neurons are highly stimulated. In this situation
>60% of the neurotransmitters susceptible to MAO degradation and
aldehyde formation originate from the active release and reuptake
of neurotransmitters and <40% are from the
non-specific leaking of vesicles. This high rate of firing can be
pathogenic because it significantly increases the formation of toxic
metabolites within the neuron and increases the risk of neurological
damage.
Neurotoxins & Autism
Many patients with autism have
high urinary levels
of
neurotransmitters indicating an increased rate of neurotransmitter
turnover. Insufficient regulation of excitatory neurotransmitters
increases the high rate of neurotransmitter release and reuptake and
increases neurotransmitter exposure to MAO.
Unchecked, excitatory neurotransmitters will cause rapid and
repeated neuron fi ring and increase neurotoxin formation.
Interventions that reduce high rates of neurotransmitter turnover
will also reduce the formation of toxic aldehydes and as a
consequence can reduce neurological damage.
Raising the level of inhibitory neurotransmitters will
decrease the rate of firing and decrease aldehyde formation. Because
over-stimulation results in the formation of toxic compounds and
neurological damage, it may also contribute to the development of
symptoms seen in autistic patients. Urinary testing of
neurotransmitter levels confirms that supporting the inhibitory
neurotransmitters with Targeted Amino Acid Therapy (TAAT) will
reduce the excretion of excitatory neurotransmitters.
Case Study:Autism & TAAT
• Patient: M
• DOB:
9/21/00
• History: Diagnosed Autistic with significant hand
flapping and low social interaction
• Medications: None
Introduction:
The patient's mother was searching for a
treatment program that would decrease or eliminate her son's
handflapping, a common symptom in autistic patients. The mother also
was hoping to develop her son's social skills, particularly his
ability to communicate verbally. The doctor ordered a urine test to
identify neurotransmitter imbalances.
Summary:
Many autistic
patients have elevated urinary catecholamine (dopamine,
norepinephrine, and epinephrine) levels, indicating a high rate of
neurotransmitter turnover.
Supporting inhibitory neurotransmitters
with a TAAT program has been shown to decrease urinary levels of
catecholamines and therefore is a method to decrease the rate
of catecholamine turnover. TAAT can be used to decrease the rate of
neurotoxic aldehyde formation by MAO, and reduce the risk of further
neurological damage in patients with autism.
References:
1. Burke WJ, Li SW,
Williams EA, Nonneman R, Zahm DS. 3,4-Dihydroxyphenylacetaldehyde is
the toxic dopamine
metabolite in vivo: implications for
Parkinson's disease pathogenesis. Brain Res. 2003 Nov
7;989(2):205-
13.
2. Eisenhofer G, Kopin IJ, Goldstein DS.
Leaky catecholamine stores: undue waste or a stress response
coping
mechanism? Ann N Y Acad Sci. 2004 Jun;1018:224-30.
| 
