Neuroscience
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Recent work identified novel progestin signaling molecules, including progesterone receptor membrane component 1 (Pgrmc1), Pgrmc2, serpine mRNA binding protein 1 (Serbp1), progestin and adiponectin receptors 7 (Paqr7) and Paqr8. These molecules mediate rapid progesterone (P(4)) effects in non-neural tissue and we recently mapped their expression in the brain. Many rapid effects of P(4) require 17β-estradiol (E(2)) and P(4) priming; therefore, we examined the effects of ovarian hormones on the expression of these non-classical progestin signaling molecules. ⋯ Finally, in the VMNvl, P(4) increased mRNA levels encoding Pgrmc1, Pgrmc2 and Serbp1, and the combination of E(2) and P(4) increased Pgrmc1 and Serbp1 mRNA levels. Paqr7 was not regulated by E(2) or P(4) in any brain region examined. In summary, we showed that ovarian hormones regulate novel progestin signaling molecules in brain regions important for the neuroendocrine control of reproduction.
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Traditionally studies aimed at elucidating the molecular mechanisms underlying cerebellar motor learning have been focused on plasticity at the parallel fiber to Purkinje cell synapse. In recent years, however, the concept is emerging that formation and storage of memories are both distributed over multiple types of synapses at different sites. ⋯ In addition, we demonstrate that these NR2A(-/-) mutants as well as mutants in which the C terminal in the NR2A subunit is selectively truncated (NR2A(ΔC/ΔC) mice) have deficits in phase reversal adaptation of their vestibulo-ocular reflex (VOR), while their basic eye movement performance is similar to that of wild type littermates. These results indicate that NMDA-NR2A mediated potentiation at the mossy fiber to granule cell synapse is not required for basic motor performance, and they raise the possibility that it may contribute to some forms of vestibulo-cerebellar memory formation.
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Borneol, a terpene and bicyclic organic compound found in several species, can easily penetrate the blood-brain barrier (BBB) and helps the absorption of many agents through BBB in the brain, but there has been no study about its direct action on neurons in the CNS. In the present study, we used an in vitro ischemic model of oxygen-glucose deprivation followed by reperfusion (OGD/R) to investigate the neuroprotective effects of borneol and the related mechanisms. We demonstrated that borneol reversed OGD/R-induced neuronal injury, nuclear condensation, intracellular reactive oxygen species (ROS) generation, and mitochondrial membrane potential dissipation. ⋯ In conclusion, our study indicated that borneol protects against cerebral ischemia/reperfusion injury through multifunctional cytoprotective pathways. The mechanisms of this reversal from OGD/R may be involved in the alleviation of intracellular ROS and iNOS/NO pathway, inhibition of inflammatory factor release and depression of caspase-related apoptosis. Among these effects, the inhibition of IκBα-NF-κB and translocation signaling pathway might play a significant role in the neuroprotection of borneol.
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Cortical malformations are commonly associated with intractable epilepsy and other developmental disorders. Our studies utilize the tish rat, a spontaneously occurring genetic model of subcortical band heterotopia (SBH) associated with epilepsy, to evaluate the developmental events underlying SBH formation in the neocortex. Our results demonstrate that Pax6(+) and Tbr2(+) progenitors are mislocalized in tish(+/-) and tish(-/-)- neocortex throughout neurogenesis. ⋯ However, vimentin immunohistochemistry indicates that the radial glial scaffold is disrupted in the region of the tish(-/-) heterotopia. Moreover, lineage tracing experiments using in utero electroporation in tish(-/-) neocortex demonstrate that mislocalized progenitors do not retain contact with the ventricular surface and that ventricular/subventricular zone (SVZ) progenitors produce neurons that migrate into both the heterotopia and cortical plate (CP). Taken together, these findings define a series of developmental errors contributing to SBH formation that differs fundamentally from a primary error in neuronal migration.