Endoplasmic reticulum (ER) stress is involved in Alzheimer's disease (AD), but the mechanism is not fully understood. Here, we injected tunicamycin (TM), a recognized ER stress inducer, into the brain ventricle of Sprague‐Dawley (SD) rats to induce the unfolded protein response (UPR), demonstrated by the enhanced phosphorylation of pancreatic ER kinase (PERK), inositol‐requiring enzyme‐1 (IRE‐1) and activating transcription factor‐6 (ATF‐6). We observed that UPR induced spatial memory deficits and impairments of synaptic plasticity in the rats. After TM treatment, GSK‐3β was activated and phosphorylation of cAMP response element binding protein at Ser129 (pS129‐CREB) was increased with an increased nuclear co‐localization of pY126‐GSK‐3β and pS129‐CREB. Simultaneous inhibition of GSK‐3β by hippocampal infusion of SB216763 (SB) attenuated TM‐induced UPR and spatial memory impairment with restoration of pS129‐CREB and synaptic plasticity. We concluded that UPR induces AD‐like spatial memory deficits with mechanisms involving GSK‐3β/pS129‐CREB pathway.

Background: Alzheimer disease (AD) is the most common type of dementia which is becoming a primary problem in the present society, but it lacks effective treatment methods and means of AD. Tanshinone IIA (Tan IIA) has been reported to have neuroprotective effects to restrain the Aβ_{25 -35}-mediated apoptosis. However, few studies try to understand how Aβ_1-42 affects hyperphosphorylation of tau and how Tan IIA regulates this process at the molecular level. Methods: Fifty male Sprague-Dawley rats were randomly divided into 5 groups and infused through the lateral ventricle with Aβ_1-42 except the control group. Then the rats were treated with Tan IIA through intragastric administration for 4 weeks. After the ability of learning and memory being measured, histomorphological examination and Western blot were used to detect the possible mechanism in the AD-associated model rats. Results: We observed that Aβ_1-42 infusion could induce spatial learning and memory deficits in rats. Simultaneously, Aβ_1-42 also could reduce the neuron in cornu ammonis 1 and dentate gyrus of hippocampus, as well as increase the levels of cleaved caspase 3, hyperphosphorylated tau at the sites Ser396, Ser404, and Thr205 with enhancing staining of black granules in brain. We also found that Aβ_1-42 could increase the activity of extracellular signal-regulated protein kinase (ERK) and glycogen synthase kinase-3β (GSK-3β). Meanwhile, these phenomena could be ameliorated when Tan IIA was used. Conclusion: We concluded that Tan IIA might have neuroprotective effect and improving learning and memory ability to be a viable candidate in AD therapy with mechanisms involving the ERK and GSK-3β signal pathway.

Aging is a complex and inevitable biological process affected by a combination of external environmental and genetic factors. Humans are currently living longer than ever before, accompanied with aging-related alterations such as diminished autophagy, decreased immunological function, mitochondrial malfunction, stem cell failure, accumulation of somatic and mitochondrial DNA mutations, loss of telomere, and altered nutrient metabolism. Aging leads to a decline in body functions and age-related diseases, for example, Alzheimer's disease, which adversely affects human health and longevity. The quality of life of the elderly is greatly diminished by the increase in their life expectancy rather than healthy life expectancy. With the rise in the age of the global population, aging and related diseases have become the focus of attention worldwide. In this review, we discuss several major mechanisms of aging, including DNA damage and repair, free radical oxidation, telomeres and telomerase, mitochondrial damage, inflammation, and their role in neurodegenerative diseases to provide a reference for the prevention of aging and its related diseases.

As current efforts have limited effects on the clinical outcome of intracerebral hemorrhage (ICH), the mechanisms including microglia/macrophages that involved inflammation need further investigation. Here, 0.4 units of collagenase VII were injected into the left caudate putamen (CPu) to duplicate ICH rat models. In the brains of ICH rats, microglia/macrophages, the nearest cells to the hemorrhagic center, were observed as ameboid and Prussian-blue positive. Furthermore, the ameboid microglia/macrophages were differentiation (CD) 68 and interleukin-1β (IL-1β) positive, and neither CD206 nor chitinase3-like 3 (Ym1) positive, suggesting their strong abilities of phagocytosis and secretion of IL-1β. According to the distance to the hemorrhagic center, we selected four areas—I, II, III, and IV—to analyze the morphology of microglia/macrophages. The processes decreased successively from region I to region IV. Microglia/macrophages in region IV had no processes. The processes in region I were radially distributed, however, they showed obvious directivity towards the hemorrhagic center in regions II and III. Region III had the largest density of compactly arrayed microglia/macrophages. All these in vivo results present the high morphologic plasticity of microglia/macrophages and their functions in the pathogenesis of ICHs.