Hormonal Receptors and Synaptic Plasticity

Study Notes

NMDA receptor activation plays a role in estradiol-induced signaling pathways within neurons.
In CA1 pyramidal neurons, estradiol activates PI3 kinase, enhancing actin polymerization and promoting filopodia outgrowth, which may form synaptic connections.
PI3 kinase activation leads to the translation of PSD-95 in dendrites, crucial for spine synapse maturation.
Key signaling mechanisms involved include LIM kinase, cofilin phosphorylation, and the Rac/Rho signaling pathway.
Cofilin pathways are significant for spinogenesis in the ventromedial hypothalamus, influencing lordosis behavior.

Progesterone causes rapid down-regulation of estradiol-induced spine synapses after their formation.
The progesterone receptor antagonist Ru486 interferes with the normal down-regulation of estradiol-induced spines during the estrous cycle.

Historical efforts isolated peptide releasing factors in the hypothalamus, indicating receptor mechanisms for hormones from gonads, adrenal glands, and thyroid.
Identification of nuclear hormone receptors in peripheral tissues led to discoveries of similar receptors in the hypothalamus and pituitary gland.
Estrogens and androgens activate receptors in the hypothalamus, influencing sexual behavior.
Research revealed estrogen receptors are present in brain regions beyond the hypothalamus, affecting various behaviors including motor control and mood.

Glucocorticoid receptors were first identified in the hippocampus, emphasizing its role in memory and behavior regulation.
Significant density of GluN1 NMDA receptors is observed in hypertensive male and aged female mice, with a decrease in non-hypertensive young females.
AngII-induced hypertension in experimental models correlates with increased GluN1 receptor presence in neurons containing ERβ.

Hypertension linked to AngII is associated with superoxide production by NADPH oxidase (NOX) neurons within the paraventricular nucleus (PVN).
In male models, AngII hypertension leads to alterations in p47phox distribution and increased reactive oxygen species (ROS) production.
Sex differences noted in the hypothalamus regarding neurohumoral regulation of blood pressure; post-menopausal females exhibit different p47phox distribution compared to young females and males.

The cerebellum exhibits responsiveness to estrogens, producing estradiol and progesterone, and is involved in sex-differentiated disorders.
Estrogens regulate dendritic growth in the cerebellum and affect excitatory/inhibitory balance, influencing motor coordination, memory, and mood.
Although neuronal counts are similar, disorders such as autism and ADHD show varying prevalence between sexes, with greater impact noted in males.

Podcast Beta