The crucial role that hippocampus Cyclooxygenase-2 plays in memory.

It is generally accepted that Cyclooxygenase-2 (COX-2) is activated to cause inflammation. However, COX-2 is also constitutively expressed at the postsynaptic dendrites and excitatory terminals of the cortical and spinal cord neurons. Although some evidence suggests that COX-2 release during neuronal signalling may be pivotal for regulating the function of memory, the significance of constitutively expressed COX-2 in neuron is still unclear. This research aims to discover the role of COX-2 in memory beyond neuroinflammation and to determine whether the inhibition of COX-2 can cause cognitive dysfunction by influencing dendritic plasticity and its underlying mechanism. We found COX-2 gene knockout (KO) could significantly impact the learning and memory ability, cause neuronal structure disorder and influence gamma oscillations. These might be mediated by the inhibition of prostaglandin (PG) E2/cAMP pathway and phosphorylated protein kinase A (p-PKA)-phosphorylated cAMP response element binding protein (p-CREB)-brain derived neurotrophic factor (BDNF) axis. It suggested COX-2 might play a critical role in learning, regulating neuronal structure and gamma oscillations in the hippocampus CA1 by regulating COX-2/BDNF signalling pathway.

Pain sensitivity related to gamma oscillation of parvalbumin interneuron in primary somatosensory cortex in Dync1i1-/- mice.

Cytoplasmic dynein is an important intracellular motor protein that plays an important role in neuronal growth, axonal polarity formation, dendritic differentiation, and dendritic spine development among others. The intermediate chain of dynein, encoded by Dync1i1, plays a vital role in the dynein complex. Therefore, we assessed the behavioral and related neuronal activities in mice with dync1i1 gene knockout. Neuronal activities in primary somatosensory cortex were recorded by in vivo electrophysiology and manipulated by optogenetic and chemogenetics. Nociception of mechanical, thermal, and cold pain in Dync1i1-/- mice were impaired. The activities of parvalbumin (PV) interneurons and gamma oscillation in primary somatosensory were also impaired when exposed to mechanical nociceptive stimulation. This neuronal dysfunction was rescued by optogenetic activation of PV neurons in Dync1i1-/- mice, and mimicked by suppressing PV neurons using chemogenetics in WT mice. Impaired pain sensations in Dync1i1-/- mice were correlated with impaired gamma oscillations due to a loss of interneurons, especially the PV type. This genotype-driven approach revealed an association between impaired pain sensation and cytoplasmic dynein complex.

Altered pain sensitivity in 5×familial Alzheimer disease mice is associated with dendritic spine loss in anterior cingulate cortex pyramidal neurons.

ABSTRACT: Chronic pain is highly prevalent. Individuals with cognitive disorders such as Alzheimer disease are a susceptible population in which pain is frequently difficult to diagnosis. It is still unclear whether the pathological changes in patients with Alzheimer disease will affect pain processing. Here, we leverage animal behavior, neural activity recording, optogenetics, chemogenetics, and Alzheimer disease modeling to examine the contribution of the anterior cingulate cortex (ACC) neurons to pain response. The 5× familial Alzheimer disease mice show alleviated mechanical allodynia which can be regained by the genetic activation of ACC excitatory neurons. Furthermore, the lower peak neuronal excitation, delayed response initiation, as well as the dendritic spine reduction of ACC pyramidal neurons in 5×familial Alzheimer disease mice can be mimicked by Rac1 or actin polymerization inhibitor in wild-type (WT) mice. These findings indicate that abnormal of pain sensitivity in Alzheimer disease modeling mice is closely related to the variation of neuronal activity and dendritic spine loss in ACC pyramidal neurons, suggesting the crucial role of dendritic spine density in pain processing.

Limit Equilibrium Method-based Shear Strength Prediction for Corroded Reinforced Concrete Beam with Inclined Bars.

Shear strength is a widely investigated parameter for reinforced concrete structures. The corrosion of reinforcement results in shear strength reduction. Corrosion has become one of the main deterioration factors in reinforced concrete beam. This paper proposes a shear strength model for beams with inclined bars based on a limit equilibrium method. The proposed model can be applied to both corroded and uncorroded reinforced concrete beams. Besides the tensile strength of longitudinal steel bars, the shear capacity provided by the concrete on the top of the diagonal crack, the tensile force of the shear steel at the diagonal crack, the degradation of the cross-sectional area and strength of the reinforcements induced by corrosion are all considered. An experimental work on two groups accelerated corroded beams was performed. Good agreements were found between the proposed theoretical predictions and experimental observations.

Static and Fatigue Behavior Investigation of Artificial Notched Steel Reinforcement.

Pitting corrosion is one of the most common forms of localized corrosion. Corrosion pit results in a stress concentration and fatigue cracks usually initiate and propagate from these corrosion pits. Aging structures may fracture when the fatigue crack reaches a critical size. This paper experimentally simulates the effects of pitting morphologies on the static and fatigue behavior of steel bars. Four artificial notch shapes are considered: radial ellipse, axial ellipse, triangle and length-variable triangle. Each shape notch includes six sizes to simulate a variety of pitting corrosion morphologies. The stress-strain curves of steel bars with different notch shape and depth are obtained based on static tensile testing, and the stress concentration coefficients for various conditions are determined. It was determined that the triangular notch has the highest stress concentration coefficient, followed by length-variable triangle, radial ellipse and axial ellipse shaped notches. Subsequently, the effects of notch depth and notch aspect ratios on the fatigue life under three stress levels are investigated by fatigue testing, and the equations for stress range-fatigue life-notch depth are obtained. Several conclusions are drawn based on the proposed study. The established relationships provide an experimental reference for evaluating the fatigue life of concrete bridges.