De Novo Synthesized Estradiol: A Role in Modulating the Cerebellar Function

The estrogen estradiol is a potent neuroactive steroid that may regulate brain structure and function. Although the effects of estradiol have been historically associated with gonadal secretion, the discovery that this steroid may be synthesized within the brain has expanded this traditional concept. Indeed, it is accepted that de novo synthesized estradiol in the nervous system (nE2) may modulate several aspects of neuronal physiology, including synaptic transmission and plasticity, thereby influencing a variety of behaviors. These modulations may be on a time scale of minutes via non-classical and often membrane-initiated mechanisms or hours and days by classical actions on gene transcription. Besides the high level, recent investigations in the cerebellum indicate that even a low aromatase expression can be related to the fast nE2 effect on brain functioning. These pieces of evidence point to the importance of an on-demand and localized nE2 synthesis to rapidly contribute to regulating the synaptic transmission. This review is geared at exploring a new scenario for the impact of estradiol on brain processes as it emerges from the nE2 action on cerebellar neurotransmission and cerebellum-dependent learning.