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Pulling it All Together. Internal Milieu. External Milieu. Synaptic Self. Psychological Milieu. Three Interacting Components Internal Milieu ~ Our Physiology External Milieu ~ Environmental Exposure Psychological Milieu ~ Mental Trilogy. (Thinking, Emotions, Motivation).

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pulling it all together
Pulling it All Together

Internal Milieu

External Milieu

Synaptic Self

Psychological Milieu

Three Interacting Components

Internal Milieu ~ Our Physiology

External Milieu ~ Environmental Exposure

Psychological Milieu ~ Mental Trilogy

(Thinking, Emotions, Motivation)

epigenetics microgenetics

Where the Internal Milieu meets the External Milieu:

Epigenetics & Microgenetics

Epigenetics: Study of heritable changes in gene expression that occur without a change in DNA sequence. This “extra” layer (or “epi”) of transcriptional control regulates how genes are expressed. (Rodeniser & Mann, 2006, CMAJ, 174, 341-348)

note: The epigenetic process occurs before transcription

Microgenetics: Study of small RNA molecules (microRNA) that can negatively control their target expression post-transcriptionally (Chuang & Jones, 2007)

note: the mircrogenetic process occurs after transcription

what does this mean
What does this mean?

Genetic expression (DNA) controls our physiology


Microgenetics and Epigenetics control the expression of our DNA.

This can occur before the transcription of RNA (epigenetics) or after the transcription of RNA (microgenetics). Typically they are thought of as separate and independent processes, but a current theory is that they are interconnected (Chuang & Jones, 2007, Pediatric Research, 61, 24-29).

Lets start with the expression of DNA, in basic terms…


DNA Expression: Transcription to Protein Synthesis




Protein Synthesis

From: fajerpc.magnet.fsu.edu/Education/2010/Lecture...



Small (micro) RNA molecules made up of ~22 nucleotides are made at the same time mRNA is made (left side). These come from the “noncoding” part of the DNA (introns).

420 different microRNAs have been identified to date.

microRNAs alter the translation and stability of mRNA (by turning gene sequences on and off) and are linked to aging, cancer and anti-apoptosis events.



Diagram from: Rodeniser & Mann, 2006


This process occurs before mRNA transcription and directly affects the DNA/histone complex (chromatin).

Only unmethylated portions of the DNA can begin transcription.

When sequences on the DNA are methylated (i.e. cytosine receives a methyl group – as one cause), the DNA portion becomes silenced in an aberrant way.

The problem arises because the necessary proteins (histones) to regulate (turn on) gene expression are NOT made PLUS the methylated gene sequence becomes susceptible to mutation.

What controls the methylation process? Diet, stress, etc. and who knows what else…

again what does this mean
Microgenetic changes can lead to an array of disorders any time during one’s life.

Epigenetic changes can lead to an array of disorders prenatally, postnatally and possibly in future generations.

Again, What Does this Mean?


Epigenetic mechanisms (DNA methylation and histone modification) can affect the expression of microRNAs… (Chuang & Jones, 2007)

food for thought
Food for thought:
  • Microgenetic changes alter (down-regulate) Brain Derived Neurotrophic Factor (BDNF; Schratt et al., 2006, Nature, 283-289)
  • Loss of BDNF reduces synaptic plasticity (Berton & Nestler, 2006, Nature Reviews, 137-151).
  • Hormones/peptides associated with stress decrease BDNF activity (Berton & Nestler, 2006)
  • Stress and its accompany neurochemical changes are Epigenetic factors (Fish, et al., 2004, Annals of New York Academy of Sciences, 167-179)
  • Epigenetic mechanisms influence microgenetic mechanisms (Chuang & Jones, 2007)

Might this be ONE of the processes from which genetic abnormalities are transferred from one generation to another?

Might this the etiology of mental illness in the diathesis-stress model?

Might this be how Fluoride and other toxins affect gene expression, health and off-spring?

Might this be the direction of future therapeutic interventions in the area of mental illness in addition to somatic diseases?

Might this be the totality of the who we are, which underlies the “Synaptic Self”?

Some answers?

The Ghost in Your Genes (BBC presentation)