Difference between revisions of "Serotoninergic, GABAergic, and glutamatergic pathways"

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'''GABAergic pathway'''
 
'''GABAergic pathway'''
  
 
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Abnormalities in the GABAergic system have been found the platelets of all of the autistic children in one study, which makes some researchers hypothesize that the elevated plasma GABA levels result because of hyposensitivity of a subset of GABA recepters.  Presynaptic cells increase GABA release to compensate  for the subsets' decreased sensitivity, but this in consequently results in increased post-synaptic activation of other normal GABA receptor subtypes.<sup>4</sup>
  
 
'''Glutamatergic pathway'''
 
'''Glutamatergic pathway'''
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3. West L et. al. '''Review of the evidence for treatment of children with autism with selective serotonin reuptake inhibitors.''' J Spec Pediatr Nurs. 2009 Jul;14(3):183-91. PMID 19614827
 
3. West L et. al. '''Review of the evidence for treatment of children with autism with selective serotonin reuptake inhibitors.''' J Spec Pediatr Nurs. 2009 Jul;14(3):183-91. PMID 19614827
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4. Schmitz, C. et. al. '''Autism: neuropathology, alterations of the GABAergic system, and animal models.''' Int Rev Neurobiol. 2005;71:1-26. PMID 16512344

Revision as of 15:56, 19 November 2009

Serotoninergic, GABAergic, and Glutamatergic pathways

Serotoninergic pathway

Serotonin platelet levels are elevated in 25-33% of people with autism, which indicates that serotonin may be associated with the pathophysiology of autism.3 One group, Chugani et. al. has demonstrated that there are developmental differences in serotonin synthesis capacity between those with autism and those without. Global brain values for autistic children, non-autistic children, and epileptic children without autism were obtained and trajectories were plotted for serotonin synthesis capacity. It was found that for non-autistic children, serotonin synthesis capacity was greater than 200% of adult capacity until 5 years, when capacity then started declining until it reaches adult values. For autistic children, serotonin synthesis capacity gradually increased between 2-11 years of age to 1 and a half times the normal values of an adult.

Pharmacological and knock-out experiments with mice show that serotonin can also affect synaptogenesis. There is transient serotonergic innervation of the primary sensory cortex between postnatal days 2-14 during the period of synaptogenesis in the rat cortex. There is transient expression of high-affinity serotonin transporter and vesicular monoamine transporter by glutamergic thalamocortical neurons. Thalamo-cortical neurons take up and store serotonin during this period but do not synthesis the neurotransmitter. Depletion of serotonin stores delays the development of the barrel fields of the rat somatosensory cortex and decreases the size of barrel fields. Too much serotonin results in incrased tangential arborization of these axons resulting in the blurring of boundaries between cortical barrels.

There is also evidence that changes in the serotonin receptor 5HT1A can affect the brain regions that are abnormal in autism.2Although the exact relationship between serotonin and autism is not known, research suggests that the change in thalamo-cortico connections may result from severatl types of 5-HT transporters, a decreased central response to 5-HT, or diminished binding to 5-HT receptors.3


GABAergic pathway

Abnormalities in the GABAergic system have been found the platelets of all of the autistic children in one study, which makes some researchers hypothesize that the elevated plasma GABA levels result because of hyposensitivity of a subset of GABA recepters. Presynaptic cells increase GABA release to compensate for the subsets' decreased sensitivity, but this in consequently results in increased post-synaptic activation of other normal GABA receptor subtypes.4

Glutamatergic pathway







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References

1. Pardo, CA et. al. The Neurobiology of Autism.Brain Pathol. 2007 Oct;17(4):434-47. PMID 17919129

2. Chugani DC.Role of altered brain serotonin mechanisms in autism.Mol Psychiatry. 2002;7 Suppl 2:S16-7. PMID 12142936

3. West L et. al. Review of the evidence for treatment of children with autism with selective serotonin reuptake inhibitors. J Spec Pediatr Nurs. 2009 Jul;14(3):183-91. PMID 19614827

4. Schmitz, C. et. al. Autism: neuropathology, alterations of the GABAergic system, and animal models. Int Rev Neurobiol. 2005;71:1-26. PMID 16512344