CATCH 22: DO You have enough ATP to run all those synapses & that 'Hyper-Plastic' brain?

Val's Take/Conjecture

• It was just a few years ago that everyone was talking about "Brain Plasticity."
• I thought that was so cool UNTIL I came across the research that people with ADHD & Autism often have HYPER-PLASTIC BRAINS.

This idea of "BRAIN ENERGY" is linking some things together such as MICROGLIA DYSTREGULATION and EMOTIONAL DYSREGULATION,

• Neuro-Diverse folks are often very bright in one or more respects and struggling to keep it together.

Neuron-Glia Interactions in Neurodevelopmental Disorders (2020)

​Abstract

​Recent studies have revealed synaptic dysfunction to be a hallmark of various psychiatric diseases, and that glial cells participate in synapse formation, development, and plasticity.

Glial cells contribute to neuroinflammation and synaptic homeostasis, the latter being essential for maintaining the physiological function of the central nervous system (CNS).

In particular, glial cells undergo gliotransmission and regulate neuronal activity in tripartite synapses via ion channels (gap junction hemichannel, volume regulated anion channel, and bestrophin-1), receptors (for neurotransmitters and cytokines), or transporters (GLT-1, GLAST, and GATs) that are expressed on glial cell membranes.

In this review, we propose that dysfunction in neuron-glia interactions may contribute to the pathogenesis of neurodevelopmental disorders.

Understanding the mechanisms of neuron-glia interaction for synapse formation and maturation will contribute to the development of novel therapeutic targets of neurodevelopmental disorders.

Glutamate and microglia activation as a driver of dendritic apoptosis: a core pathophysiological mechanism to understand schizophrenia (2021)

Val's Take:  What I'm trying to say is that there is a DISCONNECT between the ENERGY NEEDS of NEURO-DIVERSE BRAINS and the ENERGY that is actually available to them due to dysregulation of Microglia and Mitchondria IN UTERO.

Further, there are other Glial cells such as Astrocytes and they seem to be maintaining glutamate homeostasis in the Central Nervous System.

Surprise, Surprise --- This also seems to be DYSREGULATED for those who experienced Maternal Immune Activation.

​Abnormal Brain Bioenergetics in First-Episode Psychosis (2021)

In addition to understanding:

• Maternal Immune Activation
• BRAIN ENERGY &
• Microglia ----

How does this relate to "HOMEOSTASIS"?

One of the things the researchers are doing is they are getting to the CELLULAR and MOLECULAR PATHWAY LEVEL and finding that:

• Dysregulations occurred IN UTERO via Maternal Immune Activation  which had epigenetic consequences and various "DYSREGULATIONS" pre-natally.
• This often involves:
  • Microglia,
  • Mitchondria (and ATP production),
  • Astrocytes, 
  • And Glutamate which is associated with "NEURONAL EXCITOTOXITY"

Why do Neuro-Diverse folks have excess Glutamate?

​Glutamate-Mediated Excitotoxicity in the Pathogenesis and Treatment of Neurodevelopmental and Adult Mental Disorders (2024)

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​Astrocytes Maintain Glutamate Homeostasis in the CNS by Controlling the Balance between Glutamate Uptake and Release (2019)

Specialized astrocytes mediate glutamatergic gliotransmission in the CNS (2023)

​Maternal Immune Activation imprints translational dysregulation and differential MAP2 phosphorylation in descendant neural stem cells (2024)