Neurosteroid Production Decline is the age-related reduction in the de novo synthesis of steroid hormones within the central nervous system, independent of peripheral endocrine gland output. Neurosteroids, such as allopregnanolone and DHEA, are critical for modulating neurotransmitter activity, supporting mood regulation, enhancing memory, and promoting neurogenesis. This decline compromises the brain’s local homeostatic mechanisms, contributing to age-associated cognitive impairment, increased anxiety, and vulnerability to neurological disorders. Addressing this deficit is a key strategy in neuroendocrine-focused anti-aging protocols.
Origin
This concept arose following the identification of steroid-synthesizing enzymes in glial cells and neurons, distinguishing locally produced neurosteroids from those transported from peripheral glands. The term highlights the distinct, localized endocrine function within the nervous system. The ‘decline’ component reflects the observed reduction in these compounds with advancing chronological age.
Mechanism
The mechanism involves the reduced activity or expression of key steroidogenic enzymes, such as cytochrome P450 side-chain cleavage enzyme and 3-beta-hydroxysteroid dehydrogenase, within the brain and spinal cord. The resultant lower concentration of neurosteroids leads to insufficient positive allosteric modulation of GABA-A receptors and NMDA receptors, impairing inhibitory and excitatory balance, respectively. This diminished modulation compromises the brain’s stress response, reduces synaptic resilience, and accelerates age-related neurophysiological deterioration.
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