Astrocytes are implicated in information processing, signal transmission, and regulation of synaptic plasticity. Aquaporin-4 (AQP4) is the major water channel in adult brain and is primarily expressed in astrocytes. A growing body of evidence indicates that AQP4 is a potential molecular target for the regulation of astrocytic function. However, little is known about the role of AQP4 in synaptic plasticity in the amygdala. Therefore, we evaluated long-term potentiation (LTP) in the lateral amygdala (LA) and associative fear memory of AQP4 knockout (KO) and wild-type mice. We found that AQP4 deficiency impaired LTP in the thalamo-LA pathway and associative fear memory. Furthermore, AQP4 deficiency significantly downregulated glutamate transporter-1 (GLT-1) expression and selectively increased NMDA receptor (NMDAR)-mediated EPSCs in the LA. However, low concentration of NMDAR antagonist reversed the impairment of LTP in KO mice. Upregulating GLT-1 expression by chronic treatment with ceftriaxone also reversed the impairment of LTP and fear memory in KO mice. These findings imply a role for AQP4 in synaptic plasticity and associative fear memory in the amygdala by regulating GLT-1 expression.

Objective-Macrophage apoptosis plays important roles in atherosclerosis. Bcl-2 is a key cell survival molecule, but its role in macrophage apoptosis in atherosclerosis is not known. The goal herein was to determine the effect of macrophage-targeted deletion of Bcl-2 on macrophage apoptosis in atherosclerotic lesions of Apoe Ϫ/Ϫ mice. Methods and Results-Bcl2 flox -LysMCre mice were created as a model of macrophage Bcl-2 deficiency. Macrophages from these mice were more susceptible to apoptosis than those from control Bcl2 WT -LysMCre mice. The mice were bred onto the Apoe Ϫ/Ϫ background and fed a Western-type diet for 4 or 10 weeks. Apoptotic cells were equally very rare in the lesions of both groups of the 4-week-diet mice, and there was no difference in lesion area. However, Bcl2 flox -LysMCre;Apoe Ϫ/Ϫ plaques from the 10-week-diet protocol had a 40% to 45% increase in apoptotic cells and, in female mice, a Ϸ25% increase in plaque necrosis (PϽ0.05) compared with Bcl2 WT -LysMCre lesions. Key Words: atherosclerosis-pathophysiology Ⅲ apoptosis Ⅲ macrophage Ⅲ animal models of human disease M acrophage apoptosis can be a critical event in atherosclerosis and occurs at all stages of disease development. 1 In early lesions, macrophage apoptosis is associated with a decrease in lesion cellularity and plaque progression, 2,3 which could be attribtuable to rapid phagocytic clearance or egress of the apoptotic cells or decreased influx of macrophages. In advanced lesions, however, clearance of apoptotic cells is defective, which leads to secondary necrosis of apoptotic cells. 4 -6 Accordingly, we have proposed that macrophage apoptosis in advanced lesions leads to plaque necrosis, which is thought to promote plaque disruption and acute clinical events in humans. 7 In support of this idea, vulnerable necrotic human plaques have increased macrophage apoptosis. 8 Moreover, genetic or pharmacological manipulations that decrease macrophage apoptosis in advanced murine lesions decrease plaque necrosis, and vice versa. 9 Conclusions-Macrophage See accompanying article on page 153Bcl-2 has been on the forefront of cell survival signaling since its discovery more than 20 years ago, yet there is an absence of in vivo causation studies assessing the role of Bcl-2 in atherosclerosis using genetically altered mouse models. This point is critical, because there are a number of other cell survival molecules in lesional cells, including Bcl-xL, apoptosis inhibitor expressed by macrophages (AIM; SP␣), Mcl-1, and members of the inhibitor-of-apoptosis (IAP) family, and so redundancy might negate the effect of deletion of any one cell survival molecule. Because Bcl-2 is expressed in other lesional cell types and holo-Bcl2 Ϫ/Ϫ mice have multiple abnormalities at birth, 10 we created macrophage-targeted Bcl-2-deficient mice and studied the effect of this mutation on atherosclerosis in Western diet-fed Apoe Ϫ/Ϫ mice. Our studies indicate that macrophage Bcl-2 plays a protective role against macrophage apoptosis specifically in advanced ath...

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The significant relations observed in the current study between HS and the general psychopathological as well as cognitive symptoms suggest that decreased HS is involved in the psychopathology and cognitive deficits of schizophrenia, and it might be a promising peripheral biomarker of schizophrenia.

These results identify a key role of leptin in dampening fear conditioning-induced synaptic potentiation in the LA through NMDA receptor and indicate a new strategy for treating anxiety disorders.

Due to their excellent mechanical properties and good biocompatibility, titanium alloys have become a popular research topic in the field of medical metal implants. However, the surface of the titanium alloy does not exhibit biological activity, which may cause poor integration between the interface of the titanium implant and the interface of the bone tissue and subsequently may cause the implant to fall off. Therefore, surface biological inertness is one of the problems that titanium alloys must overcome to become an ideal orthopedic implant material. Surface modification can improve the biological properties of titanium, thereby enhancing its osseointegration effect. Copper is an essential trace element for the human body, can promote bone formation and plays an important role in maintaining the physiological structure and function of bone and bone growth and development. In this study, a microporous copper-titanium dioxide coating was prepared on the surface of titanium by microarc oxidation. Based on the evaluation of its surface characteristics, the adhesion, proliferation and differentiation of MC3T3-E1 cells were observed. A titanium rod was implanted into the rabbit femoral condyle, and the integration of the coating and bone tissue was evaluated. Our research results show that the microporous copper-titanium dioxide coating has a nearly three-dimensional porous structure, and copper is incorporated into the coating without changing the structure of the coating. In vitro experiments found that the coating can promote the adhesion, proliferation and differentiation of MC3T3-E1 cells. In vivo experiments further confirmed that the titanium copper-titanium dioxide microporous coating can promote the osseointegration of titanium implants. In conclusion, copper-titanium dioxide microporous coatings can be prepared by microarc oxidation, which can improve the biological activity and biocompatibility of titanium, promote new bone formation and demonstrate good osteoinductive properties. Therefore, the use of this coating in orthopedics has potential clinical application.