Regulator of G protein signaling 6 mediates exercise-induced recovery of hippocampal neurogenesis,learning,and memory in a mouse model of Alzheimer’s disease

Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.

A Low-Power,Single-Poly,Non-Volatile Memory for Passive RFID Tags

Single-poly,576bit non-volatile memory is designed and implemented in an SMIC 0.18μm standard CMOS process for the purpose of reducing the cost and power of passive RFID tag chips. The memory bit cell is designed with conventional single-poly pMOS transistors, based on the bi-directional Fowler-Nordheim tunneling effect, and the typical program/erase time is 10ms for every 16bits. A new ,single-ended sense amplifier is proposed to reduce the power dissipation in the current sensing scheme. The average current consumption of the whole memory chip is 0.8μA for the power supply voltage of 1.2V at a reading rate of 640kHz.

Overview of one transistor type of hybrid organic ferroelectric non-volatile memory

Organic ferroelectric memory devices based on field effect transistors that can be configured between two stable states of on and off have been widely researched as the next generation data storage media in recent years.This emerging type of memory devices can lead to a new instrument system as a potential alternative to previous non-volatile memory building blocks in future processing units because of their numerous merits such as cost-effective process,simple structure and freedom in substrate choices.This bi-stable non-volatile memory device of information storage has been investigated using several organic or inorganic semiconductors with organic ferroelectric polymer materials.Recent progresses in this ferroelectric memory field,hybrid system have attracted a lot of attention due to their excellent device performance in comparison with that of all organic systems.In this paper,a general review of this type of ferroelectric non-volatile memory is provided,which include the device structure,organic ferroelectric materials,electrical characteristics and working principles.We also present some snapshots of our previous study on hybrid ferroelectric memories including our recent work based on zinc oxide nanowire channels.

Formation of high density TiN nanocrystals and its application in non-volatile memories

Non-volatile memory based on TiN nanocrystal （TiN-NC） charge storage nodes embedded in SiO2 has been fabricated and its electrical properties have been measured. It was found that the density and size distribution of TiN-NCs can be controlled by annealing temperature. The formation of well separated crystalline TiN nano-dots with an average size of 5 nm is confirmed by transmission electron microscopy and x-ray diffraction, x-ray photoelectron spectroscopy confirms the existence of a transition layer of TiNxOy/SiON oxide between TiN-NC and SiO2, which reduces the barrier height of tunnel oxide and thereby enhances programming/erasing speed. The memory device shows a memory window of 2.5V and an endurance cycle throughout 10^5. Its charging mechanism, which is interpreted from the analysis of programming speed （dVth/dt） and the gate leakage versus voltage characteristics （Ig vs Vg）, has been explained by direct tunnelling for tunnel oxide and Fowler Nordheim tunnelling for control oxide at programming voltages lower than 9V, and by Fowler-Nordheim tunnelling for both the oxides at programming voltages higher than 9V.

Molecular dynamics simulations on the wet/dry self-latching and electric fields triggered wet/dry transitions between nanosheets:A non-volatile memory nanostructure

We design a nanostructure composing of two nanoscale graphene sheets parallelly immersed in water.Using molecular dynamics simulations,we demonstrate that the wet/dry state between the graphene sheets can be self-latched;moreover,the wet→dry/dry→wet transition takes place when applying an external electric field perpendicular/parallel to the graphene sheets(E;/E;).This structure works like a flash memory device(a non-volatile memory):the stored information(wet and dry states)of the system can be kept spontaneously,and can also be rewritten by external electric fields.On the one hand,when the distance between the two nanosheets is close to a certain distance,the free energy barriers for the transitions dry→wet and wet→dry can be quite large.As a result,the wet and dry states are self-latched.On the other hand,an E;and an E;will respectively increase and decrease the free energy of the water located in-between the two nanosheets.Consequently,the wet→dry and dry→wet transitions are observed.Our results may be useful for designing novel information memory devices.

An Overview of Non-Volatile Flip-Flops Based on Emerging Memory Technologies(Invited paper)

Low power consumption is a major issue in nowadays electronics systems. This trend is pushed by the development of data center related to cloud services and soon to the Internet of Things （IoT） deployment. Memories are one of the major contributors to power consumption. However, the development of emerging memory technologies paves the way to low-power design, through the partial replacement of the dynamic random access memory （DRAM） with the non-volatile stand-alone memory in servers or with the embedded or distributed emerging non-volatile memory in IoT objects. In the latter case, non-volatile flip-flops （NVFFs） seem a promising candidate to replace the retention latch. Indeed, IoT objects present long sleep time and NVFFs offer to save data in registers with zero power when the application is idle. This paper gives an overview of NVFF architecture flavors for various emerging memory technologies.

Design of an Electrically Written and Optically Read Non-volatile Memory Device Employing BiFeO3/Au Heterostructures with Strong Absorption Resonance

Exploiting new concepts for dense, fast, and nonvolatile random access memory with reduced energy consump- tion is a significant issue for information technology. Here we design an ＇electrically written and optically read＇ information storage device employing BiFeO3/A u heterostruetures with strong absorption resonance. The electro- optic effect is the basis for the device design, which arises from the strong absorption resonance in BiFeO3/Au heterostructures and the electrically tunable significant birefringence of the BiFeO3 film. We first construct a sim- ulation calculation of the BiFeO3/Au structure spectrum and identify absorption resonance and electro-optical modulation characteristics. Following a micro scale partition, the surface reflected light intensity of different polarization units is calculated. The results depend on electric polarization states of the BiFeO3 film, thus BiFeO3/Au heterostructures can essentially be designed as a type of electrically written and optically read infor- mation storage device by utilizing the scanning near-field optical microscopy technology based on the conductive silicon cantilever tip with nanofabricated aperture. This work will shed light on information storage technology.

Fabrication and integration of photonic devices for phase-change memory and neuromorphic computing

In the past decade,there has been tremendous progress in integrating chalcogenide phase-change materials(PCMs)on the silicon photonic platform for non-volatile memory to neuromorphic in-memory computing applications.In particular,these non von Neumann computational elements and systems benefit from mass manufacturing of silicon photonic integrated circuits(PICs)on 8-inch wafers using a 130 nm complementary metal-oxide semiconductor line.Chip manufacturing based on deep-ultraviolet lithography and electron-beam lithography enables rapid prototyping of PICs,which can be integrated with high-quality PCMs based on the wafer-scale sputtering technique as a back-end-of-line process.In this article,we present an overview of recent advances in waveguide integrated PCM memory cells,functional devices,and neuromorphic systems,with an emphasis on fabrication and integration processes to attain state-of-the-art device performance.After a short overview of PCM based photonic devices,we discuss the materials properties of the functional layer as well as the progress on the light guiding layer,namely,the silicon and germanium waveguide platforms.Next,we discuss the cleanroom fabrication flow of waveguide devices integrated with thin films and nanowires,silicon waveguides and plasmonic microheaters for the electrothermal switching of PCMs and mixed-mode operation.Finally,the fabrication of photonic and photonic–electronic neuromorphic computing systems is reviewed.These systems consist of arrays of PCM memory elements for associative learning,matrix-vector multiplication,and pattern recognition.With large-scale integration,the neuromorphic photonic computing paradigm holds the promise to outperform digital electronic accelerators by taking the advantages of ultra-high bandwidth,high speed,and energy-efficient operation in running machine learning algorithms.

A Low Power Non-Volatile LR-WPAN Baseband Processor with Wake-Up Identification Receiver

The paper proposes a low power non-volatile baseband processor with wake-up identification(WUI) receiver for LR-WPAN transceiver.It consists of WUI receiver,main receiver,transmitter,non-volatile memory(NVM) and power management module.The main receiver adopts a unified simplified synchronization method and channel codec with proactive Reed-Solomon Bypass technique,which increases the robustness and energy efficiency of receiver.The WUI receiver specifies the communication node and wakes up the transceiver to reduce average power consumption of the transceiver.The embedded NVM can backup/restore the states information of processor that avoids the loss of the state information caused by power failure and reduces the unnecessary power of repetitive computation when the processor is waked up from power down mode.The baseband processor is designed and verified on a FPGA board.The simulated power consumption of processor is 5.1uW for transmitting and 28.2μW for receiving.The WUI receiver technique reduces the average power consumption of transceiver remarkably.If the transceiver operates 30 seconds in every 15 minutes,the average power consumption of the transceiver can be reduced by two orders of magnitude.The NVM avoids the loss of the state information caused by power failure and energy waste caused by repetitive computation.

Effects of medicinal plants on Alzheimer＇s disease and memory deficits

Alzheimer＇s disease is an age-related neurodegenerative disorder characterized by memory deficits. Various studies have been carried out to find therapeutic approaches for Alzheimer＇s disease. However, the proper treatment option is still not available. There is no cure for Alzheimer＇s disease, but symptomatic treatment may improve the memory and other dementia related problems. Traditional medicine is practiced world- wide as memory enhancer since ancient times. Natural therapy including herbs and medicinal plants has been used in the treatment of memory deficits such as dementia, amnesia, as well as Alzheimer＇s disease since a long time. Medicinal plants have been used in different systems of medicine, particularly Unani system of medicines and exhibited their powerful roles in the management and cure of memory disorders. Most of herbs and plants have been chemically evaluated and their efficacy has also been proven in clinical trials. However, the underlying mechanisms of actions are still on the way. In this paper, we have reviewed the role of different medicinal plants that play an important role in the treatment of Alzheimer＇s disease and memory deficits using conventional herbal therapy.

A high methionine,low folate and vitamin B_6/B_(12) containing diet can be associated with memory loss by epigenetic silencing of netrin-1

Memory-epigenetics which is the loss of memory due to epigenetic modifications can be due to the silencing of genes involved in cognitive functions and this is the basis of the current study.We hypothesize that a diet containing high methionine and low vitamins can lead to memory impairment by increasing global DNA methylation and therefore,silencing the netrin-1 gene,which encodes the glycoprotein involved in neurogenesis,axonal guidance and maintenance of the synaptic plasticity.Wild type(C57 BL/6 J) mice were fed with a diet containing excess methionine(1.2%),low-folate(0.08 mg/kg),vitamin B_6(0.01 mg/kg),and B_(12)(10.4 mg/kg) for 6 weeks.Mice were examined weekly for the long-term memory function,using a passive avoidance test,which determined loss of fear-motivated long-term memory starting from the fourth week of diet.Similarly,an increase in brain %5-methyl cytosine was observed starting from the 4 th week of diet in mice.Mice fed with a high methionine,low folate and vitamins containing diet showed a decrease in netrin-1 protein expression and an increase in netrin-1 gene promotor methylation,as determined by methylation-sensitive restriction enzyme-polymerase chain reaction analysis.The increase in methylation of netrin-1 gene was validated by high-resolution melting and sequencing analysis.Furthermore,the association of netrin-1 with memory was established by administering netrin that considerably restored long-term fear motivated memory.Taken together,these results suggest that a diet rich in methionine and lacking in folate and vitamin B_6/B_(12) can induce defects in learning and memory.Furthermore,the data indicates that decrease in netrin-1 expression due to hyper-methylation of its gene can be associated with memory loss.The animal procedures were approved by the Institutional Animal Care and Use Committee,University of Louisville,USA(No.A3586-01) on February 2,2018.

Icariin ameliorates memory deficits through regulating brain insulin signaling and glucose transporters in 3×Tg-AD mice

Icariin,a major prenylated flavonoid found in Epimedium spp.,is a bioactive constituent of Herba Epimedii and has been shown to exert neuroprotective effects in experimental models of Alzheimer’s disease.In this study,we investigated the neuroprotective mechanism of icariin in an APP/PS1/Tau triple-transgenic mouse model of Alzheimer’s disease.We performed behavioral tests,pathological examination,and western blot assay,and found that memory deficits of the model mice were obviously improved,neuronal and synaptic damage in the cerebral cortex was substantially mitigated,and amyloid-βaccumulation and tau hyperphosphorylation were considerably reduced after 5 months of intragastric administration of icariin at a dose of 60 mg/kg body weight per day.Furthermore,deficits of proteins in the insulin signaling pathway and their phosphorylation levels were significantly reversed,including the insulin receptor,insulin receptor substrate 1,phosphatidylinositol-3-kinase,protein kinase B,and glycogen synthase kinase 3β,and the levels of glucose transporter 1 and 3 were markedly increased.These findings suggest that icariin can improve learning and memory impairments in the mouse model of Alzheimer’s disease by regulating brain insulin signaling and glucose transporters,which lays the foundation for potential clinical application of icariin in the prevention and treatment of Alzheimer’s disease.

Power-Aware Data Management Based on Hybrid RAM-NVM Memory for Smart Bracelet

Wearable devices become popular because they can help people observe health condition.The battery life is the critical problem for wearable devices. The non-volatile memory(NVM) attracts attention in recent years because of its fast reading and writing speed, high density, persistence, and especially low idle power. With its low idle power consumption,NVM can be applied in wearable devices to prolong the battery lifetime such as smart bracelet. However, NVM has higher write power consumption than dynamic random access memory(DRAM). In this paper, we assume to use hybrid random access memory(RAM)and NVM architecture for the smart bracelet system.This paper presents a data management algorithm named bracelet power-aware data management(BPADM) based on the architecture. The BPADM can estimate the power consumption according to the memory access, such as sampling rate of data, and then determine the data should be stored in NVM or DRAM in order to satisfy low power. The experimental results show BPADM can reduce power consumption effectively for bracelet in normal and sleeping modes.

Age-dependent loss of cholinergic neurons in learning and memory-related brain regions and impaired learning in SAMP8 mice with trigeminal nerve damage

The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we investigated the effects of damage to the inferior alveolar nerve, an important peripheral nerve in the trigeminal sensory pathway, on learning and memory be-haviors and structural changes in related brain regions, in a mouse model of Alzheimer’s disease. Inferior alveolar nerve transection or sham surgery was performed in middle-aged （4-month-old） or elderly （7-month-old） senescence-accelerated mouse prone 8 （SAMP8） mice. When the middle-aged mice reached 8 months （middle-aged group 1） or 11 months （middle-aged group 2）, and the elderly group reached 11 months, step-down passive avoidance and Y-maze tests of learn-ing and memory were performed, and the cholinergic system was examined in the hippocampus （Nissl staining and acetylcholinesterase histochemistry） and basal forebrain （choline acetyltrans-ferase immunohistochemistry）. In the elderly group, animals that underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1 and CA3 regions, fewer cholinergic ifbers in the CA1 and dentate gyrus, and fewer cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band, compared with sham-operated animals, as well as showing impairments in learning and memory. Conversely, no signiifcant differences in histology or be-havior were observed between middle-aged group 1 or group 2 transected mice and age-matched sham-operated mice. The present ifndings suggest that trigeminal nerve damage in old age, but not middle age, can induce degeneration of the septal-hippocampal cholinergic system and loss of hippocampal pyramidal neurons, and ultimately impair learning ability. Our results highlight the importance of active treatment of trigeminal nerve damage in elderly patients and those with Alzheimer’s disease, and indicate that tooth extraction should be avoided in these populations.

Radix Achyranthis Bidentatae improves learning and memory capabilities in ovariectomized rats

Kidney-tonifying recipe can reduce the accumulation of advanced glycation end products, prevent neuronal degeneration and improve cognitive functions in ovariectomized rats. Radix Achyranthis Bidentatae alcohol extracts may dose-dependently inhibit non-enzymatic saccharification in vitro. This study aimed to examine the effect of Radix Achyranthis Bidentatae on advanced glycation end products and on learning and memory capabilities in ovariectomized rats. Ovariectomized rats were treated with Radix Achyranthis Bidentatae alcohol extracts （containing 1.5 g/kg crude drug） or 0.1% aminoguanidine for 12 weeks and behavioral testing was performed with the Y-electrical maze. This test revealed that Radix Achyranthis Bidentatae and aminoguanidine could improve the learning and memory capabilities of ovariectomized rats. Results of competitive enzyme-linked immunosorbent assay showed that treatment with Radix Achyranthis Bidentatae or aminoguanidine reduced the accumulation of advanced glycation end products in the frontal cortex of ovariectomized rats, while increasing content in the blood and urine. Biochemical tests showed that treatment with Radix Achyranthis Bidentatae or aminoguanidine decreased superoxide dismutase activity in the serum and frontal cortex, and increased serum levels of glutathione peroxidase in ovariectomized rats. In addition there was no apparent effect on malondialdehyde levels. These experimental findings indicate that Radix Achyranthis Bidentatae inhibits production of advanced glycation end products and its accumulation in brain tissue, and improves learning and memory capabilities in ovariectomized rats. These effects may be associated with an anti-oxidative action of the extract.

Effect of Panax notoginseng saponins on the expression of beta-amyloid protein in the cortex of the parietal lobe and hippocampus, and spatial learning and memory in a mouse model of senile dementia

BACKGROUND： The pharmacological actions of Panax notoginseng saponins （PNS） lie in removing free radicals, anti-inflammation and anti-oxygenation. It can also improve memory and behavior in rat models of Alzheimer＇s disease. OBJECTIVE： Using the Morris water maze, immunohistochemistry, real-time PCR and RT-PCR, this study aimed to measure improvement in spatial learning, memory, expression of amyloid precursor protein （App） and β -amyloid （A β ）, to investigate the mechanism of action of PNS in the treatment of AD in the senescence accelerated mouse-prone 8 （SAMP8） and compare the effects with huperzine A. DESIGN, TIME AND SETTING： A completely randomized grouping design, controlled animal experiment was performed in the Center for Research ＆ Development of New Drugs, Guangxi Traditional Chinese Medical University from July 2005 to April 2007. MATERIALS： Sixty male SAMP8 mice, aged 3 months, purchased from Tianjin Chinese Traditional Medical University of China, were divided into four groups： PNS high-dosage group, PNS low-dosage group, huperzine A group and control group. PNS was provided by Weihe Pharmaceutical Co., Ltd. （batch No.： Z53021485, Yuxi, Yunan Province, China）. Huperzine A was provided by Zhenyuan Pharmaceutical Co., Ltd. （batch No.： 20040801, Zhejiang, China）. METHODS： The high-dosage group and low-dosage group were treated with 93.50 and 23.38 mg/kg PNS respectively per day and the huperzine A group was treated with 0.038 6 mg/kg huperzine A per day, all by intragastric administration, for 8 consecutive weeks. The same volume of double distilled water was given to the control group. MAIN OUTCOME MEASURES： After drug administration, learning and memory abilities were assessed by place navigation and spatial probe tests. The recording indices consisted of escape latency （time-to-platform）, and the percentage of swimming time spent in each quadrant. The number of A β 1-40, A β 1-42 and App immunopositive neurons in the brains of SAMP8 mice was analyzed by immunohistochemistry. The mRNA content ofApp, tau, acetylcholinesterase, and synaptophysin （Syp） was tested by real time PCR and RT-PCR. RESULTS： The PCR results show that PNS can downregulate the expression of the App gene and upregulate the expression of the Syp gene in the parietal cortex and hippocampus of SAMP8 mice. The therapeutic effects of the PNS high-dosage group were greater than those of the PNS low-dosage group and the huperzine A group （P 〈 0.05）. The results of the Morris water maze and immunohistochemistry indicated that PNS can improve the capacity for spatial learning and memory in SAMP8 mice, and reduce the content of A β 1-40, A β 1-42 and expression of App in the brains of SAMP8 mice. The therapeutic effects of the PNS high-dosage group were greater than that of the PNS low-dosage group and the huperzine A group （P 〈 0.05）. CONCLUSION： These results support the hypothesis that PNS plays a therapeutic and protective role on the pathological lesions and learning dysfunction of Alzheimer＇s disease. The therapeutic effects of PNS for Alzheimer＇s disease are possibly achieved through downregulating the expression of the App gene and upregulating the expression of the Syp gene. The therapeutic effects of PNS are dose-dependent and are greater than the effect of huperzine A.

Deep Language Statistics of Italian throughout Seven Centuries of Literature and Empirical Connections with Miller’s 7 ∓2 Law and Short-Term Memory

Statistics of languages are usually calculated by counting characters, words, sentences, word rankings. Some of these random variables are also the main “ingredients” of classical readability formulae. Revisiting the readability formula of Italian, known as GULPEASE, shows that of the two terms that determine the readability index G—the semantic index , proportional to the number of characters per word, and the syntactic index GF, proportional to the reciprocal of the number of words per sentence—GF is dominant because GC is, in practice, constant for any author throughout seven centuries of Italian Literature. Each author can modulate the length of sentences more freely than he can do with the length of words, and in different ways from author to author. For any author, any couple of text variables can be modelled by a linear relationship y = mx, but with different slope m from author to author, except for the relationship between characters and words, which is unique for all. The most important relationship found in the paper is that between the short-term memory capacity, described by Miller’s “7 ? 2 law” (i.e., the number of “chunks” that an average person can hold in the short-term memory ranges from 5 to 9), and the word interval, a new random variable defined as the average number of words between two successive punctuation marks. The word interval can be converted into a time interval through the average reading speed. The word interval spreads in the same range as Miller’s law, and the time interval is spread in the same range of short-term memory response times. The connection between the word interval (and time interval) and short-term memory appears, at least empirically, justified and natural, however, to be further investigated. Technical and scientific writings (papers, essays, etc.) ask more to their readers because words are on the average longer, the readability index G is lower, word and time intervals are longer. Future work done on ancient languages, such as the classical Greek and Latin Literatures (or modern languages Literatures), could bring us an insight into the short-term memory required to their well-educated ancient readers.

Protective effect of tetrahydroxy stilbene glucoside on learning and memory by regulating synaptic plasticity

Damage to synaptic plasticity induced by neurotoxicity of amyloid-beta is regarded to be one of the pathological mechanisms of learning and memory disabilities in Alzheimer＇s disease patients. This study assumed that the damage of amyloid-beta to learning and memory abilities was strongly associated with the changes in the Fyn/N-methyl-D-aspartate receptor 2B （NR2B） expression. An APP695V7171 transgenic mouse model of Alzheimer＇s disease was used and treatment with tetrahydroxy-stilbene glucoside was administered intragas- trically. Results showed that intragastric administration of tetrahydroxy-stilbene glucoside improved the learning and memory abilities of the transgenic mice through increasing NR2B receptors and Fyn expression. It also reversed parameters for synaptic interface structure of gray type I. These findings indicate that tetrahydroxy stilbene glucoside has protective effects on the brain, and has prospects for its clinical application to improve the learning and memory abilities and treat Alzheimer＇s disease.

Mathematical Models of Emotional Robots with a Non-Absolute Memory

In this paper, we discuss questions of creating an electronic intellectual analogue of a human being. We introduce a mathematical concept of stimulus generating emotions. We also introduce a definition of logical thinking of robots and a notion of efficiency coefficient to describe their efficiency of rote (mechanical) memorizing. The paper proves theorems describing properties of permanent conflicts between logical and emotional thinking of robots with a nonabsolute rote memory.

STAT3 ameliorates truncated tau-induced cognitive deficits

Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s disease patients.Nonetheless,the molecular mechanisms of truncated tau-induced cognitive deficits remain unclear.Evidence suggests that signal transduction and activator of transcription-3(STAT3)is associated with modulating synaptic plasticity,cell apoptosis,and cognitive function.Using luciferase reporter assays,electrophoretic mobility shift assays,western blotting,and immunofluorescence,we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the nucleus.Overexpression of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss,thereby improving the cognitive deficits in tau-N368 mice.Moreover,in tau-N368 mice,activation of STAT3 increased N-methyl-D-aspartic acid receptor levels,decreased Bcl-2 levels,reversed synaptic damage and neuronal loss,and thereby alleviated cognitive deficits caused by tau-N368.Taken together,STAT3 plays a critical role in truncated tau-related neuropathological changes.This indicates a new mechanism behind the effect of tau-N368 on synapses and memory deficits.STAT3 can be used as a new molecular target to treat tau-N368-induced protein pathology.