Synaptic Plasticity

BDNF Signalling

Brain-derived neurotrophic factor acting at TrkB. The growth signal behind new synapses and behind the kind of memory that needs sleep to form. It is suppressed by sustained cortisol and by lost deep sleep, which is how a compound with no direct action in the brain still reaches memory.

Dendritic Spine Density

How many connection points a neuron carries. Spines appear and disappear over hours, and their number is the physical substrate of how much a circuit can currently hold. Estradiol raises spine density in hippocampal CA1, and the effect tracks the hormone.

G Protein-Coupled Estrogen Receptor

A membrane estrogen receptor separate from ER-alpha and ER-beta. It responds in seconds, which is why some estrogen effects in the brain appear far too fast to be explained by gene transcription.

Glutamate Signalling

The brain's main excitatory signal. Everything fast the brain does runs on it, and too much of it is how neurons die. Long-term users show a chemical signature consistent with raised turnover, which is the nearest thing to direct human evidence of a neurotoxic process in this literature.

NMDA Glutamate Receptor

The receptor that carries the calcium current behind learning. It is also the route by which too much glutamate kills the cell, so the same channel that writes memory is the one that destroys the neuron when it stays open too long.

Verbal Memory

Recall of words, names and conversation. Studied in testosterone trials in older men with mixed and generally small results, which is worth stating plainly: this is one of the few cognitive measures here with any controlled human data at all, and the data does not show a large effect.

Neuroinflammation

Immune activation inside brain tissue. Short bursts are protective. Sustained activation is not, and it limits the very functions the immune cells were maintaining. Estrogen is one of the main brakes on it, which is the mechanistic core of why crashing estrogen has a cost.