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BackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by an abnormal accumulation of amyloid-β (Aβ) plaques, neuroinflammation, and impaired neurogenesis. Urolithin A (UA), a gut-microbial metabolite of ellagic acid, has been reported to exert anti-inflammatory effects in the brain. However, it is unknown whether UA exerts its properties of anti-inflammation and neuronal protection in the APPswe/PS1ΔE9 (APP/PS1) mouse model of AD.MethodsMorris water maze was used to detect the cognitive function. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was performed to detect neuronal apoptosis. Immunohistochemistry analyzed the response of glia, Aβ deposition, and neurogenesis. The expression of inflammatory mediators were measured by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). The modulating effects of UA on cell signaling pathways were assayed by Western blotting.ResultsWe demonstrated that UA ameliorated cognitive impairment, prevented neuronal apoptosis, and enhanced neurogenesis in APP/PS1 mice. Furthermore, UA attenuated Aβ deposition and peri-plaque microgliosis and astrocytosis in the cortex and hippocampus. We also found that UA affected critical cell signaling pathways, specifically by enhancing cerebral AMPK activation, decreasing the activation of P65NF-κB and P38MAPK, and suppressing Bace1 and APP degradation.ConclusionsOur results indicated that UA imparted cognitive protection by protecting neurons from death and triggering neurogenesis via anti-inflammatory signaling in APP/PS1 mice, suggesting that UA might be a promising therapeutic drug to treat AD.

BackgroundEndogenously produced hydrogen sulfide (H2S) may have multiple functions in brain. An increasing number of studies have demonstrated its anti-inflammatory effects. In the present study, we investigated the effect of sodium hydrosulfide (NaHS, a H2S donor) on cognitive impairment and neuroinflammatory changes induced by injections of Amyloid-β1-40 (Aβ1-40), and explored possible mechanisms of action.MethodsWe injected Aβ1-40 into the hippocampus of rats to mimic rat model of Alzheimer’s disease (AD). Morris water maze was used to detect the cognitive function. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was performed to detect neuronal apoptosis. Immunohistochemistry analyzed the response of glia. The expression of interleukin (IL)-1β and tumor necrosis factor (TNF)-α was measured by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). The expression of Aβ1-40, phospho-p38 mitogen-activated protein kinase (MAPK), phospho-p65 Nuclear factor (NF)-κB, and phospho-c-Jun N-terminal Kinase (JNK) was analyzed by western blot.ResultsWe demonstrated that pretreatment with NaHS ameliorated learning and memory deficits in an Aβ1-40 rat model of AD. NaHS treatment suppressed Aβ1-40-induced apoptosis in the CA1 subfield of the hippocampus. Moreover, the over-expression in IL-1β and TNF-α as well as the extensive astrogliosis and microgliosis in the hippocampus induced by Aβ1-40 were significantly reduced following administration of NaHS. Concomitantly, treatment with NaHS alleviated the levels of p38 MAPK and p65 NF-κB phosphorylation but not JNK phosphorylation that occurred in the Aβ1-40-injected hippocampus.ConclusionsThese results indicate that NaHS could significantly ameliorate Aβ1-40-induced spatial learning and memory impairment, apoptosis, and neuroinflammation at least in part via the inhibition of p38 MAPK and p65 NF-κB activity, suggesting that administration of NaHS could provide a therapeutic approach for AD.

Area prostriata (Pro) has been found to play important roles in the rapid processing of moving stimuli in the far peripheral visual field. However, the specific neural substrates responsible for these functions remain unknown. In this study, we first examined the location, extent, and topography of the rodent equivalent of the primate Pro based on cytoarchitecture and molecular markers. We then identified its intimate connections with the primary visual cortex (V1) using retrograde and anterograde tracers. Our main finding is that medial V1, which receives peripheral visual information, has strong reciprocal connections with the Pro in both rat and mouse while lateral V1 has significantly fewer such connections. The direct V1 inputs to the Pro provide at least one of the shortest pathways for visual information to reach the Pro, and may be crucial to the fast processing of unexpected stimuli in the peripheral visual field.

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