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Acute stress elevates the levels of inhibitory neurosteroids like allopregnanolone, and these neurosteroids are known to counteract many of the effects of stress. [32] This is similar to the case of endorphins , which are released in response to stress and physical pain and counteract the negative subjective effects of such states.
This is a list of neurosteroids, or natural and synthetic steroids that are active on the mammalian nervous system through receptors other than steroid hormone receptors. It includes inhibitory , excitatory , and neurotrophic neurosteroids as well as pheromones and vomeropherines .
Pregnenolone and its 3β-sulfate, pregnenolone sulfate, like dehydroepiandrosterone (DHEA), DHEA sulfate, and progesterone, belong to the group of neurosteroids that are found in high concentrations in certain areas of the brain, and are synthesized there. Neurosteroids affect synaptic functioning, are neuroprotective, and enhance myelinization.
Little is known about where different complexes are located in the brain, complicating drug discovery. [7] For example, the binding site of neurosteroids in the GABA A receptor is not known [9] and barbiturates bind at a beta subunit that is distinct from the benzodiazepine binding site.
A neurosteroidogenesis inhibitor is a drug that inhibits the production of endogenous neurosteroids.Neurosteroids include the excitatory neurosteroids pregnenolone sulfate, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEA-S), and the inhibitory neurosteroids allopregnanolone, tetrahydrodeoxycorticosterone (THDOC), and 3α-androstanediol, among others. [1]
Many commonly used sedative and anxiolytic drugs that affect the GABA receptor complex are not agonists. These drugs act instead as positive allosteric modulators (PAMs) and while they do bind to the GABA receptors, they bind to an allosteric site on the receptor and cannot induce a response from the neuron without an actual agonist being present.
The key cellular components of the neuroimmune system are glial cells, including astrocytes, microglia, and oligodendrocytes. [1] [2] [5] Unlike other hematopoietic cells of the peripheral immune system, mast cells naturally occur in the brain where they mediate interactions between gut microbes, the immune system, and the central nervous system as part of the microbiota–gut–brain axis.
Allopregnanolone is a metabolic intermediate in an androgen backdoor pathway from progesterone to dihydrotestosterone, which occurs during normal male fetus development; placental progesterone in the male fetus is the feedstock of this pathway; deficiencies in this pathway lead to insufficient virilization of the male fetus.