Locally Synthesized 17-Beta-Estradiol Reverses Amyloid-Beta-42-Induced Hippocampal Long-Term Potentiation Deficits

    January 2024 in “ International journal of molecular sciences ”
    Laura Bellingacci, Jacopo Canonichesi, Miriam Sciaccaluga, Alfredo Megaro, Petra Mazzocchetti, Michela Di Mauro, Cinzia Costa, Massimiliano Di Filippo, Vito Enrico Pettorossi, Alessandro Tozzi
    TLDR A brain-made hormone can protect against memory-related brain damage caused by harmful proteins.
    The study investigated the role of neural-derived 17β-estradiol (nE2) in counteracting the neurotoxic action of Amyloid beta 1-42 (Aβ42) on hippocampal long-term potentiation (LTP), a process important for memory and learning. The researchers found that increasing nE2 synthesis from testosterone using finasteride completely recovered LTP in slices treated with soluble Aβ42 aggregates. Additionally, modulation of the glutamate N-methyl-D aspartate receptor (NMDAR) by memantine effectively rescued the LTP deficit observed in slices exposed to Aβ42. The study concludes that nE2 could potentially serve as a neuroprotective agent in cerebral amyloidosis, counteracting the early loss of synaptic plasticity associated with Aβ aggregates’ accumulation.
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