Sulforaphane attenuates apoptosis of hippocampal neurons induced by high glucose via regulating endoplasmic reticulum.

Diabetic encephalopathy (DE) has been defined as one of the major complications of diabetes, characterized by neurochemical and neurodegenerative changes. However, the molecular mechanism of DE are not fully elucidated at present. Here, the primary hippocampal neurons were cultured in vitro with high glucose (HG) to induce diabetes-like effects, and mice were given streptozotocin (STZ) to induce a model of type 1 diabetes mellitus (T1D) mice. The administration of sulforaphane (SF) were used to observe the protective effects on the hippocampal neurons. We found that the expression of glucose-regulated protein 78 (GRP78), a typical endoplasmic reticulum chaperone, showed a trend of increasing in the early phase but decreasing in the late phase of both HG-induced primary hippocampal neurons and T1D mice. However, SF suppressed the apoptosis induced by HG in vitro and in vivo through TUNEL assay and caspase-3 immunohistochemistry staining. Meanwhile, the administration of SF suppressed the upregulation of CHOP, Bax and p-JNK protein and the downregulation of Bcl-2 protein induced by HG in hippocampal neurons in vitro and in vivo. The caspase-12 gene was upregulated only at 4 weeks in T1D mice compared with control mice, and the upregulation was suppressed by SF. In addition, the combined administration of SF and PX12, which is an inhibitor of thioredoxin (Trx), eliminated the protective effects of SF. We conclude that HG induced the development of endoplasmic reticulum stress (ERS) in hippocampal neurons, eventually leading to the apoptosis of neurons. SF prevented the ERS and attenuates the hippocampal neuron apoptosis induced by HG both in vitro and in vivo. The underlying mechanism may be involved in the suppression of the CHOP-Bax/Bcl-2, JNK and caspase-12 signaling pathways by SF through the Trx-1 target protein.

Antioxidant effects of Lycium barbarum polysaccharides on photoreceptor degeneration in the light-exposed mouse retina.

We assessed the neuroprotective effects of Lycium barbarum Polysaccharides (LBP) on photoreceptor degeneration and the mechanisms involved in oxidative stress in light-exposed mouse retinas. Mice were given a gavage of LBP (150 mg/kg or 300 mg/kg) or phosphate buffered saline (PBS) for 7 days before exposure to light (5000 lx for 24 h). We found that LBP significantly improved the electroretinography (ERG) amplitudes of the a- and b-waves that had been attenuated by light exposure. In addition, changes caused by light exposure including photoreceptor cell loss, nuclear condensation, an increased number of mitochondria vacuoles, outer membrane disc swelling and cristae fractures were distinctly ameliorated by LBP. LBP treatment also significantly prevented the generation of reactive oxygen species (ROS) compared with PBS treatment. The levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and thioredoxin reductase (TrxR1) mRNA were decreased in PBS-treated mice compared with controls but increased remarkably in LBP-treated mice. The mRNA levels of the DNA repair gene Poly (ADP-ribose) polymerase (PARP14) was increased in PBS-treated mice but decreased significantly in the LBP-treated mice. Our findings indicate that pretreatment with LBP effectively protected photoreceptor cells against light-induced retinal damage probably through the up-regulation of the antioxidative genes Nrf2 and TrxR1, the elimination of oxygen free radicals, and the subsequent reduction in the mitochondrial reaction to oxidative stress and enhancement in antioxidant capacity. In addition, the decreased level of PARP14 mRNA in LBP-treated mice also indicated a protective effect of LBP on delaying photoreceptor in the light-damaged retina.

Neural stem cells over-expressing brain-derived neurotrophic factor promote neuronal survival and cytoskeletal protein expression in traumatic brain injury sites.

Cytoskeletal proteins are involved in neuronal survival. Brain-derived neurotrophic factor can increase expression of cytoskeletal proteins during regeneration after axonal injury. However, the effect of neural stem cells genetically modified by brain-derived neurotrophic factor transplantation on neuronal survival in the injury site still remains unclear. To examine this, we established a rat model of traumatic brain injury by controlled cortical impact. At 72 hours after injury, 2 × 107 cells/mL neural stem cells overexpressing brain-derived neurotrophic factor or naive neural stem cells (3 mL) were injected into the injured cortex. At 1-3 weeks after transplantation, expression of neurofilament 200, microtubule-associated protein 2, actin, calmodulin, and beta-catenin were remarkably increased in the injury sites. These findings confirm that brain-derived neurotrophic factor-transfected neural stem cells contribute to neuronal survival, growth, and differentiation in the injury sites. The underlying mechanisms may be associated with increased expression of cytoskeletal proteins and the Wnt/ß-catenin signaling pathway.