Living and Adapting to Its Own Habitat - Building the Most Complex Structure on Earth - page 208

of high-LG mothers from those of low-LG mothers appear between the first and
sixth day and include increased synthesis of the neurotransmitter serotonin and GR
expression, particularly in the hippocampus area. This coincides with a period of
time in which differences in the maternal LG behavior are apparent, clearly suggest-
ing that “the sensory input associated with maternal LG selectively alters 5-HT activ-
ity in specific brain regions” ( Meaney and Szyf, 2005b ).
Investigators relate this to the presence of an enzymatic machinery of methyla-
tion/demethylation in hippocampal neurons ( Meaney and Szyf, 2005a ). Figure 4.6
schematically depicts the structure of the epigenetic machinery responsible for
maternal care and the flow of the epigenetic information along the machinery. It
shows that the afferent information on maternal tactile stimuli induces the secretion
of serotonin in the puppy's hippocampal neurons, which is followed by the dem-
ethylation of the nerve-growth-factor-inducible factor-A (NGFI-A), also known as
zenk or egr-1, and of the exon 1 7 promoter of the GR gene. This enables binding
of NGFI-A to the exon promoter, thus inducing GR expression ( Figure 4.6 ). The
increased synthesis of GR, in a feedback, acts as an antistress factor. It decreases
the secretion of the stress hormone/neurotransmitter corticotropin-releasing hormone
(CRH) and the activity of the hypothalamic-pituitary-adrenal (HPA) axis. The sensi-
tivity of the brain to stressful stimuli is diminished.

GCs feedback to the brain

Brain

Processing of the
maternal tactile stimuli
in the cerebral cortex

Adrenal
gland

Secretion of serotonin
in hipocampal neurons

Serotonin

Serotonin
receptor

Binding of serotonin
receptor

Cytoplasm

Pituitary

Secretion of NGFI-A

NGFI-A

NGtFI-A
gene

GR gene

GR synthesis

Nucleus

GR

GR

Hipocampal neuron

Figure 4.6 Simplified representation of the neural mechanism of demethylation of the GR
gene and GR synthesis in high-LG mother rats. Abbreviations : ACTH, adrenocorticotropic
hormone; CRH, corticotropin -releasing hormone; GC, glucocorticoids; GR, glucocorticoid
receptor; NGFI-A, nerve growth factor-induced clone A.