Neurosteroids in developmental disorders

Steroids play several vital roles in the central nervous system. Some of these steroids, called neurosteroids, are synthesized within the brain by the glial cells. The main neurosteroid is allopregnanolone, a metabolite of progesterone. We will describe neuronal aspects of neurosteroids activity and draw implications for their possible roles in brain development. During late fetal and early postnatal life, steroids influence the differentiation, the connectivity and the survival of specific neuronal populations in both the brain and the spinal cord. Later on neurosteroids are also able to influence neuronal activity within large parts of the nervous system, mainly by regulating synaptic transmission, either by binding to membrane receptors for neurotransmitters such as GABA_A or glutamate or by increasing the transcription of specific genes after binding to intracellular receptors. Therefore due to the participation of neurosteroids in GABAergic and glutamatergic transmission we will review their possible involvement in developmental psychiatric conditions. Moreover, we will investigate whether abnormal neurosteroids synthesis could be linked to seizures disorders. We measured in tuberous sclerosis complex epileptic children at different ages the plasma concentrations of neurosteroids and found significantly lower levels of the GABA_A active neurosteroid allopregnanolone compared with control subjects.