BackgroundCompelling evidence has shown that diabetic metabolic disorder plays a critical role in the pathogenesis of Alzheimer’s disease, including increased expression of β-amyloid protein (Aβ) and tau protein. Evidence has supported that minocycline, a tetracycline derivative, protects against neuroinflammation induced by neurodegenerative disorders or cerebral ischemia. This study has evaluated minocycline influence on expression of Aβ protein, tau phosphorylation, and inflammatory cytokines (interleukin-1β and tumor necrosis factor-α) in the brain of diabetic rats to clarify neuroprotection by minocycline under diabetic metabolic disorder.MethodAn animal model of diabetes was established by high fat diet and intraperitoneal injection of streptozocin. In this study, we investigated the effect of minocycline on expression of Aβ protein, tau phosphorylation, and inflammatory cytokines (interleukin-1β and tumor necrosis factor-α) in the hippocampus of diabetic rats via immunohistochemistry, western blotting, and enzyme-linked immunosorbent assay.ResultsThese results showed that minocycline decreased expression of Aβ protein and lowered the phosphorylation of tau protein, and retarded the proinflammatory cytokines, but not amyloid precursor protein.ConclusionOn the basis of the finding that minocycline had no influence on amyloid precursor protein and beta-site amyloid precursor protein cleaving enzyme 1 which determines the speed of Aβ generation, the decreases in Aβ production and tau hyperphosphorylation by minocycline are through inhibiting neuroinflammation, which contributes to Aβ production and tau hyperphosphorylation. Minocycline may also lower the self-perpetuating cycle between neuroinflammation and the pathogenesis of tau and Aβ to act as a neuroprotector. Therefore, the ability of minocycline to modulate inflammatory reactions may be of great importance in the selection of neuroprotective agents, especially in chronic conditions like diabetes and Alzheimer’s disease.

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By employing some modification to the widely used two-flavor Polyakov-loop extended Nambu-Jona-Lasinio (PNJL) model, we discuss the Wigner solution of the quark gap equation at finite temperature and zero quark chemical potential beyond the chiral limit, and then we try to explore its influence on the chiral and deconfinement phase transitions of QCD at finite temperature and zero chemical potential. The discovery of the coexistence of the Nambu and the Wigner solutions of the quark gap equation with nonzero current quark mass at zero temperature and zero chemical potential, as well as their evolutions with temperature, is very interesting for the studies of the phase transitions of QCD. According to our results, the chiral phase transition might be of first order (while the deconfinement phase transition is still a crossover, as in the normal PNJL model), and the corresponding phase transition temperature is lower than that of the deconfinement phase transition, instead of coinciding with each other, which are not the same as the conclusions obtained from the normal PNJL model. In addition, we also discuss the sensibility of our final results on the choice of model parameters.In the non-perturbative regime of Quantum Chromodynamics (QCD), chiral symmetry breaking and quark color confinement are of great importance and continuous interest for studying the QCD phase diagram. However, their relation is not yet clarified directly from the first principles of QCD. Generally speaking, color confinement indicates chiral symmetry breaking, while the reverse is not necessarily true. How these two phenomena are related to each other and whether (and/or under which conditions) these two transitions coincide when the temperature and/or quark chemical potential a e-mail: zonghs@chenwang.nju.edu.cn grow larger have been speculated and discussed by many people via many a model, for example, see Refs. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. Strictly speaking, chiral and deconfinement phase transitions only occur in opposite sectors in QCD. Chiral symmetry is an exact global symmetry only when the current quark mass m q is zero (the chiral limit). In the low-temperature and lowchemical potential phase (hadronic phase, often referred to as Nambu-Goldstone phase or Nambu phase), this symmetry is spontaneously broken, and as a consequence there exist N 2 f − 1 pseudoscalar Nambu-Goldstone bosons, meanwhile the QCD vacuum hosts a chiral condensate (two quark condensate) qq , which acts as an order parameter for chiral phase transition. However, the Z (3) center symmetry associated with the color confinement is exact only in the limit of pure-gauge QCD, which means m q → ∞, and so of course is too far from our real world. In the high-temperature, deconfinement phase (the Wigner phase, where the quarkgluon plasma, or QGP, is expected to appear) of QCD, this symmetry is spontaneously broken; the Polyakov loop [17], which is related to the heavy quark free energy, can serve as an order parameter for the deconf...