In adult mammalian brain, occurrence of the synthesis of estradiol from endogenous cholesterol has been doubted because of the inability to detect dehydroepiandrosterone synthase, P45017␣. In adult male rat hippocampal formation, significant localization was demonstrated for both cytochromes P45017␣ and P450 aromatase, in pyramidal neurons in the CA1-CA3 regions, as well as in the granule cells in the dentate gyrus, by means of immunohistochemical staining of slices. Only a weak immunoreaction of these P450s was observed in astrocytes and oligodendrocytes. ImmunoGold electron microscopy revealed that P45017␣ and P450 aromatase were localized in pre-and postsynaptic compartments as well as in the endoplasmic reticulum in principal neurons. The expression of these cytochromes was further verified by using Western blot analysis and RT-PCR. Stimulation of hippocampal neurons with N-methyl-D-aspartate induced a significant net production of estradiol. Analysis of radioactive metabolites demonstrated the conversion from [ 3 H]pregnenolone to [ 3 H]estradiol through dehydroepiandrosterone and testosterone.This activity was abolished by the application of specific inhibitors of cytochrome P450s. Interestingly, estradiol was not significantly converted to other steroid metabolites. Taken together with our previous finding of a P450scc-containing neuronal system for pregnenolone synthesis, these results imply that 17␤-estradiol is synthesized by P45017␣ and P450 aromatase localized in hippocampal neurons from endogenous cholesterol. This synthesis may be regulated by a glutamate-mediated synaptic communication that evokes Ca 2؉ signals.

Patients with Parkinson's disease (PD) can develop mild cognitive impairment (PD-MCI), frequently progressing to dementia (PDD). Here, we aimed to elucidate the relationship between white matter alteration and cognitive status in PD and dementia with Lewy bodies (DLB) by using diffusion tensor imaging. We also compared the progression patterns of white and gray matter and the cerebral perfusion. We enrolled patients with PD cognitively normal (PD-CogNL, n = 32), PD-MCI (n = 28), PDD (n = 25), DLB (n = 29), and age- and sex-matched healthy control subjects (n = 40). Fractional anisotropy (FA) map of a patient group was compared with that of control subjects by using tract-based spatial statistics. For the patient cohort, intersubject voxel-wise correlation was performed between FA values and Mini-Mental Status Examination (MMSE) scores. We also evaluated the gray matter and the cerebral perfusion by conducting a voxel-based analysis. There were significantly decreased FA values in many major tracts in patients with PD-MCI, PDD, and DLB, but not in PD-CogNL, compared with control subjects. FA values in the certain white matter areas, particularly the bilateral parietal white matter, were significantly correlated with MMSE scores in patients with PD. Patients with PDD and DLB had diffuse gray matter atrophy. All patient groups had occipital and posterior parietal hypoperfusion when compared with control subjects. Our results suggest that white matter damage underlies cognitive impairment in PD, and cognitive impairment in PD progresses with functional alteration (hypoperfusion) followed by structural alterations in which white matter alteration precedes gray matter atrophy.

This work reports the first demonstration that corticosterone (CORT) has a rapid and transient effect on NMDA receptormediated Ca 2+ signaling in cultured rat hippocampal neurons. These results imply that high levels of CORT induce a rapid and non-genomic prolongation of NMDA receptor-mediated Ca 2+ elevation, probably via putative membrane surface receptors for CORT in the hippocampal neurons.

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Our results suggest that patients with iNPH have altered microstructures in the CST. Quantitative and visual CST evaluation by using DTI may be useful for differentiating patients with iNPH from patients with AD or PDD or healthy subjects.

Corneolimbal stem/progenitor cells are significantly reduced after depletion of sensory nerves. The data suggest a critical role of innervation in maintaining stem cells and/or the stem cell niche.

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The normal corneal epithelium is endowed with CD11c(+) Langerin+ cells that are LCs, whereas the stroma is endowed with a separate population of (non-LC) Langerin+ DCs. These findings should henceforth facilitate the examination of Langerin-expressing DC subsets in the immunopathogeneses of conditions such as keratoconjunctivitis sicca, allergic keratoconjunctivitis, and corneal allograft rejection.