Poster Presentation The International Congress of Neuroendocrinology 2014

Neuronal luteinizing hormone receptor activation affects synaptic plasticity (#197)

Jeff Blair 1 , Xinglong Wang 2 , Jared Cregg 3 , Jerry Silver 3 , Gemma Casadesus 4
  1. School of Biomedical Sciences, Kent State University, Kent, Ohio
  2. Department of Pathology, Case Western Reserve University, Cleveland, Ohio
  3. Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio
  4. Department of Biological Sciences, Kent State University, Kent, Ohio

Previously, we and others have shown that reducing serum luteinizing hormone (LH) levels in ovariectomized rodents increases cognitive function and dendritic spine number.  Furthermore, we have observed that LH is produced endogenously within the brain and that its levels oppose serum LH levels, such that after ovariectomy the levels of brain LH are lowest.  This suggests that loss of LH receptor (LHR) activation, derived from reduced levels of brain LH after ovariectomy, may be a mediator of cognition and neuroplasticity loss associated with menopause.  The LHR, is a GPCR classically known to be a key component of reproductive function. LHR stimulation by LH and human chorionic gonadotropin (hCG) leads to activation of cAMP and PI3K pathways, both key pathways in neuroplasticity and cognition. Therefore, and given the broad expression of LHR in the brain, we investigated whether LHR activation could drive cellular signaling associated with the synaptic plasticity changes that were previously observed in vivo. Using primary neuronal cultures we observed that LHR activation increased GSK3β phosphorylation and β-catenin protein levels, both important in spine/synapse formation and remodeling. Furthermore, we found that LHR activation increased the number of secondary neurites. Taken together, these data suggest that LHR activation increases signaling events associated with synaptic plasticity and regulates neuronal morphology in primary culture.  Given the role of these cellular aspects on learning and memory, our data suggest that LHR activation may be a key regulator of cognition.