Long-term potentiation-based screening identifies neuronal PYGM as a synaptic plasticity regulator participating in Alzheimer's disease

Synaptic dysfunction is an important pathological hallmark and cause of Alzheimer's disease(AD).High-frequency stimulation(HFS)-induced long-term potentiation(LTP)has been widely used to study synaptic plasticity,with impaired LTP found to be associated with AD.However,the exact molecular mechanism underlying synaptic plasticity has yet to be completely elucidated.Whether genes regulating synaptic plasticity are altered in AD and contribute to disease onset also remains unclear.Herein,we induced LTP in the hippocampal CA1 region of wildtype(WT)and AD model mice by administering HFS to the CA3 region and then studied transcriptome changes in the CA1 region.We identified 89 genes that may participate in normal synaptic plasticity by screening HFS-induced differentially expressed genes(DEGs)in mice with normal LTP,and 43 genes that may contribute to synaptic dysfunction in AD by comparing HFS-induced DEGs in mice with normal LTP and AD mice with impaired LTP.We further refined the 43 genes down to 14 by screening for genes with altered expression in pathological-stage AD mice without HFS induction.Among them,we found that the expression of Pygm,which catabolizes glycogen,was also decreased in AD patients.We further demonstrated that down-regulation of PYGM in neurons impaired synaptic plasticity and cognition in WT mice,while its overexpression attenuated synaptic dysfunction and cognitive deficits in AD mice.Moreover,we showed that PYGM directly regulated energy generation in neurons.Our study not only indicates that PYGM-mediated energy production in neurons plays an important role in synaptic function,but also provides a novel LTP-based strategy to systematically identify genes regulating synaptic plasticity under physiological and pathological conditions.

Changes in microstructure and properties of weld heat-affected zone of high-strength low-alloy steel

The evolution of the microstructure and toughness of APL5L X80 pipeline steel after thermal welding simulation was investigated by X-ray diffraction,electron backscatter diffraction,and transmission electron microscopy.The results indicated that primary heat-affected zones can be divided into weld,coarse-grained,fine-grained,intercritical,and sub-critical zones.The microstructure of the weld zone is mainly composed of bainitic ferrite and a small amount of granular bainite;however,the original austenite grains are distributed in the columnar grains.The structure of the coarse-grained zone is similar to that of the weld zone,but the original austenite grains are equiaxed.In contrast,the microstructure in the fine-grained zone is dominated by fine granular bainite,and the effective grain size is only 8.15μm,thus providing the highest toughness in the entire heat-affected zone.The intercritical and subcritical zones were brittle valley regions,and the microstructure was dominated by granular bainite.However,the martensite-austenite(M/A)constituents are present in island chains along the grain boundaries,and the coarse size of the M/A constituents seriously reduces the toughness.The results of the crack propagation analyzes revealed that high-angle grain boundaries can significantly slow down crack growth and change the crack direction,thereby increasing the material toughness.The impact toughness of the low-temperature tempering zone was equivalent to that of the columnar grain zone,and the impact toughness was between those of the critical and fine-grained zones.