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Targeting the Glutamatergic System to Develop Novel, Improved Therapeutics for Mood Disorders

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Not sure if anyone has come across this. I am working through it slowly.. my knowledge is modest so taking me a while to debunk the jargon. Nonetheless, seems highly relevant and I wonder if those with more knowledge might find some new ideas to research.



Overall, this focus on monoaminergic systems has not yet greatly advanced our understanding of the biology underlying recurrent mood disorders. Any such understanding must include an explanation for the tendency towards episodic and often profound mood disturbance that can become progressive over time. These observations suggest that although monoaminergic neurotransmitter systems play an important role in the pathophysiology and treatment of mood disorders, other systems that regulate synaptic and neural plasticity are more central to the neurobiology and treatment of these disorders


Abnormal function of the glutamatergic system has been implicated in the pathophysiology of many different disorders including amyotrophic lateral sclerosis (ALS), Huntington’s chorea, epilepsy, Alzheimer’s disease, schizophrenia, and anxiety disorders. Thus, dysfunction of glutamatergic neurotransmission may be a common pathophysiological mechanism, aspects of which are shared between several disorders.



Particularly take a look at the last bit 'Emerging promise of novel therapeutics'




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Nice one Syntheso!
Yes, it is true that the latest experiments and inventions have been targeting gutamatergic transmission.
I think someone her thought that a cyclical glutamergic excitotoxicity might be what was perpetuating HPPD, but don't quote me on that.
However, there's a difference between glutamine and glutamate! Yes: it is dizzying.
Fun fact: high doses of L-Glutamine are anxiolytic.
Basically though, glutamate is the most important excitatory neurotransmitter.

From wiki:

 In brain injury or disease, they can work in reverse, and excess glutamate can accumulate outside cells. This process causes calcium ions to enter cells via NMDA receptor channels, leading to neuronal damage and eventual cell death, and is called excitotoxicity. The mechanisms of cell death include

  • Glu/Ca2+-mediated promotion of transcription factors for pro-apoptotic genes, or downregulation of transcription factors for anti-apoptotic genes

Excitotoxicity due to excessive glutamate release and impaired uptake occurs as part of the ischemic cascade and is associated with stroke[4] and diseases like amyotrophic lateral sclerosis,lathyrismautism, some forms of mental retardation, and Alzheimer's disease.[4][14] In contrast, decreased glutamate release is observed under conditions of classical phenylketonuria[15] leading to developmental disruption of glutamate receptor expression.[16]

Glutamic acid has been implicated in epileptic seizures. Microinjection of glutamic acid into neurons produces spontaneous depolarisations around one second apart, and this firing pattern is similar to what is known as paroxysmal depolarizing shift in epileptic attacks. This change in the resting membrane potential at seizure foci could cause spontaneous opening of voltage-activated calcium channels, leading to glutamic acid release and further depolarization[citation needed].

Well hey there, did that just say mitochondrial and excitotoxic damage from excess intracellular Calcium??
Awesome, didn't know that! So mitochondrial support (Resveratrol) could definitely aid in the mitigation thereof.
Anyway; it appears glutamate, calcium and seizural activity are all interrelated. So there's some food for thought :)

Thanks Syntheso!

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