INTRODUCTION:Neuropeptide Y (NPY) exerts neuroprotective effects; however, its functional relationship with autophagy-related signaling pathways in AD-associated cognitive dysfunction remains insufficiently understood. Using an Aβ-induced rat model of AD, the present study evaluated the effects of NPY on learning and memory. Specifically, we examined whether pharmacological manipulation with 3-methyladenine and MHY1485 modifies the cognitive effects of NPY, providing an indirect behavioral-pharmacological assessment of processes potentially related to autophagy and mTOR signaling. METHODS:This experimental study was conducted on 88 male Wistar rats (200-250 g) randomly divided to 11 groups (n = 8 per group). An intracerebroventricular (ICV) injection of Aβ (2 µg/µl per rat) was used to induce the AD model. NPY (10 ng /µl), MHY1485 (an mTOR activator; 2 µM), and 3-methyladenine (3-MA; an autophagy inhibitor; 300 nmol, 30 nmol, and 3 µmol) were administered via ICV injection. Cognitive performance was assessed using the passive avoidance and Y-maze tasks. RESULTS:NPY administration significantly decreased time spent in the dark compartment (TDC), increased step-through latency (STL) in the passive avoidance task, and enhanced spontaneous alternation behavior in the Y-maze (P < 0.05). Importantly, administration of MHY1485 and 3-MA (300 nM), either alone or in combination, significantly attenuated the cognitive-enhancing effects of NPY (P < 0.05) CONCLUSION: NPY improved cognitive performance in an Aβ-induced rat model of Alzheimer's disease. Our behavioral-pharmacological findings suggest that autophagy-related signaling contributes to the memory-enhancing effects of NPY. Pharmacological modulation with 3-MA and MHY1485 provides functional evidence consistent with the potential involvement of Beclin-1- and mTOR-related signaling, although direct molecular confirmation warrants further investigation.

Objective(s): Several studies have reported that the lncRNA Nuclear-enriched abundant transcript 1 (NEAT1) is associated with the progression of Alzheimer's disease (AD). Oxidative stress and apoptosis also play crucial roles in the development of AD. The present study compared the serum levels of NEAT1, superoxide dismutase (SOD), glutathione (GSH), and P53 between individuals with AD and healthy controls. Materials and Methods: Peripheral blood samples were collected from 30 AD patients and 33 healthy controls and then centrifuged to separate serum. Total RNAs were isolated, and real-time polymerase chain reaction (RT-qPCR) was applied to determine NEAT1 gene expression. Also, Enzyme-linked immunoassays (ELISA) were conducted to measure SOD and GSH as anti-oxidant factors, and p53 as an apoptosis marker. Results: NEAT1 expression was significantly higher in AD patients than in controls (P<0.001). In addition, ROC analysis revealed that serum NEAT1 levels distinguished AD patients from healthy controls with 90% sensitivity and 84.85% specificity. Moreover, the anti-oxidant levels of SOD (P<0.0001) and GSH (P<0.05) were significantly decreased in AD patients, while P53 levels were significantly increased (P<0.05). However, no significant association was found between NEAT1 expression and the measured blood factors. Conclusion: The serum levels of NEAT1 effectively distinguished between AD patients and non-AD people, underscoring its potential as a blood-based biomarker for the development of Alzheimer's disease.

Cyclosporine A (CsA) is a powerful immunosuppressant commonly used as a prophylaxis on transplant. However, it is associated with serious effects, including cardiotoxicity. Curcumin is a bioactive compound known for its anti-oxidative, anti-inflammatory, and anti-apoptotic effects. So, the present study investigated the possible protective effect of curcumin on CsA-induced heart injury in rats, focusing on oxidative stress, autophagy, and apoptosis. A total of 32 male Wistar rats were divided into control, sham (drug solvent), CsA (30 mg/kg BW), and curcumin + CsA (40 mg/kg BW, 30 mg/kg BW, respectively) groups. After 4 weeks of treatment, the heart was isolated for molecular assays. Immunoblot detected oxidative and autophagic proteins NOX4, hsp-70, beclin-1, and LC3II. The amount of 8-OHdG was measured by ELISA and heart apoptosis was examined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining (TUNEL). At the molecular levels, CSA increased the expression of NOX-4, beclin-1, LC3b, and oHdG in heart tissue. In addition, the amount of apoptosis increased in the heart tissue. However, curcumin treatment improved heart injury by significantly downregulating NOX4, LC3b, and decreasing 8-OHdG. Also, curcumin significantly reduced the rate of myocardial apoptosis. To sum up, curcumin appears to protect against CsA-induced cardiotoxicity in rats by reducing oxidative activity, apoptosis, and regulating autophagy.

The potential role of adenosine, a natural neuroprotective agent, and its receptors in the pathogenesis of Alzheimer's disease has been proposed. The present study aims to examine the effect of administering both an A1 receptor agonist and an A2A adenosine receptor antagonist simultaneously on memory, inflammatory factors, and PSD-95 in an LPS-induced Alzheimer's disease model in rats.Fifty-six male Wistar rats were randomly divided into seven groups: Saline, LPS, Saline + Vehicle, LPS + Vehicle, LPS + SCH58261 (A2A receptor antagonist), LPS + CPA (A1 receptor agonist), LPS + SCH58261+CPA. LPS (3mg/kg/ip) was used to cause memory impairment. Treatment was performed by intraventricular injection of CPA at a dose of 700μg and SCH-58261 at 40μg for ten days. Passive avoidance and Y-maze tests were performed to examine animals’ memories. IL-10, TNF-α, and PSD-95 levels were measured in the brain using ELISA and western blot, respectively.Compared to the groups receiving each medication separately, the simultaneous administration of CPA and SCH58261 improved memory (P<0.05). Additionally, compared to the single medication groups, there was a significant increase in IL-10, PSD-95, and a significant decrease in TNF-α in the brain tissue (P<0.05).These findings suggest that the activation of A1 receptors along with A2A receptor inhibition could be a potential therapeutic strategy for Alzheimer's disease. These findings suggest that A1 receptor activation combined with A2A receptor inhibition may be a promising therapeutic approach for Alzheimer's disease.

Treatment-resistant depression (TRD), marked by persistent depressive symptoms unresponsive to standard treatments, presents a significant challenge in psychiatry. Deep brain stimulation (DBS) has emerged as a novel intervention for TRD. This study examined the impact of DBS in the olfactory bulb (OB) on depressive symptoms, local field potentials (LFPs), and the medial prefrontal cortex (mPFC)-ventral hippocampus (vHPC) connectivity. Thirty-six male Wistar rats were assigned to four groups: control, chronic mild stress (CMS), CMS + DBS, and DBS. Stereotactic surgery was performed to implant electrodes in the OB, mPFC, and vHPC. The CMS protocol was administered for 3 weeks to induce depression. Behavioral assessments included the sucrose preference test (SPT), forced swim test (FST), and open field test (OFT). During the final 4 days of CMS induction, the DBS groups received OB stimulation for one hour daily. On day 22, LFPs were recorded from the mPFC and vHPC and analyzed using MATLAB. Data were evaluated using ANOVA, with P-values ≤ 0.05 considered significant. Results indicated that three weeks of CMS reduced low-frequency gamma power in the mPFC and overall gamma power in the vHPC, along with decreased delta and theta band coherence between these regions. CMS also increased delta, theta, and alpha band power during exploration. OB-DBS improved depressive-like behaviors, enhanced low-frequency gamma power in both mPFC and vHPC, and increased delta and theta coherence. These findings suggest that depression's pathogenesis involves alterations in the mPFC-vHPC neural network, and that OB-DBS may counteract these changes, offering a potential therapeutic target for TRD.

Introduction: While the involvement of neuropeptide Y (NPY) in learning and memory, as well as the role of the Y1 receptor, are well established, the function of the Y2 receptor remains a topic of debate. While the involvement of neuropeptide Y (NPY) in learning and memory, as well as the role of the Y1 receptor, are well established, the function of the Y2 receptor remains a topic of debate. Some studies suggest that NPY may also play a role in autophagy. In our investigation, we aimed to explore whether NPY and its Y2 receptor inhibitor could influence memory modulation or affect Beclin-1 expression in a rat model of Alzheimer's disease (AD). NPY may also have a role in autophagy, according to some studies. Methods: Intracerebroventricular (i.c.v) injections of amyloid-beta (A beta 1-42, 2 mu g/mu l/ side) were used to establish an animal model of AD. NPY (10 ng/mu l, 10 mu l, i.c.v) was administered 30 minutes before the retrieval. Y2 antagonist BIIE-0246 was injected 15 minutes before NPY administration in the targeted groups. BIIE-0246 was used at three different concentrations (20 nM, 200 nM, and 2 mu M). Passive avoidance memory and novel object recognition were both evaluated. Subsequently, Beclin-1 protein expression in the hippocampus was determined using western blot analysis. Results: It was found that NPY administration improved passive avoidance and cognitive memory in animals treated with A beta. Injecting BIIE-0246 before NPY did not reverse the improving effect of NPY on passive avoidance and Novel Object Recognition memories. Furthermore, compared to sham-operated animals, A beta treatment significantly reduced the hippocampal expression of Beclin-1 protein (P <= 0.05), and neither NPY nor NPY Y2 receptor inhibitors affected Beclin-1. Conclusion: In A beta-induced memory impairment, it is thought that NPY can improve both aversive and cognitive memory. Blocking NPY Y2 receptors with BIIE-0246 did not alter NPY's memory-enhancing effect.

Objectives:Metformin, as an insulin sensitizer, is a familiar antidiabetic drug. Increasing evidence points to metformin's protective effects against Alzheimer's disease (AD). However, the mechanism is not well understood. The present study evaluated whether inhibiting AMPK and activating mTOR could stop metformin from improving memory in rats with streptozotocin (STZ) -induced Alzheimer's disease.Materials and Methods:Twelve-week-old Wistar rats, were injected 3 mg/kg STZ intracerebroventricularly on days 1 and 3 to develop the animal model. Metformin was applied orally at 100 mg/kg (17 days). Forty-five min before the retrieval phase, dorsomorphin (DM; AMPK inhibitor, 2 M) and MHY (mTOR activator, 0.1 M) were administered. Morris Water Maze (MWM) and shuttle box were utilized to measure spatial and passive avoidance memory, respectively. Congo red staining was used to identify cortical amyloid deposition.Results:The findings exhibited a considerable enhancement in spatial learning and memory in the metformin treatment group (P≤0.05). Injection of DM and MHY alone could not significantly change MWM and passive avoidance. Additionally, co-administration of DM and MHY increased escape latency (P≤0.001) and reduced the total time spent in the target quadrant (TTS) (P≤0.05) compared to the STZ+MET group during retrieval of MWM. Also, co-injection of DM and MHY increased step-through latency (STL) and decreased time spent in the dark compartment (TDC) compared to the STZ+MET group (P≤0.001).Conclusion:Metformin appears to have a therapeutic impact by activating AMPK and inactivating mTOR. As a result, it could be used as an Alzheimer's treatment strategy.

BACKGROUND:The most prominent adipokine, adiponectin (APN), has an adverse relationship with the malfunction of adipose tissue. Obesity causes a decrease in plasma APN levels, which eventually results in insulin resistance and diabetes. In this study, we assessed how the effects of APN on memory are influenced by the insulin receptor substrate-1 (IRS-1) and the mammalian target of rapamycin (mTOR) pathways.METHODS:Streptozotocin (STZ) 3 mg/kg intracerebroventricular injections on days 1 and 3 following cannulation were used to create an animal model of Alzheimer's disease. The acquisition phase was preceded by injections of MHY and adiponectin. For the passive avoidance task, the stepthrough latency and total duration in the dark compartment were recorded and evaluated, and the preference index was calculated for the novel object identification test. IRS-1 protein expression in the hippocampus was assessed by western blotting.RESULTS:STZ reduced the step-through latency (STL), which rose significantly (P≤0.001) in the APN+STZ group. The memory-improving effects of APN were reversed when MHY was administered first (P≤0.001). The STZ and APN+STZ+MHY groups both had a substantial decline in the preference index (P≤0.01). Compared to the control group, the STZ group's expression of the IRS- 1 protein was dramatically reduced (P≤0.0001). In contrast to the APN+STZ group, the MHYtreated group likewise showed decreased IRS-1 protein expression (P≤0.0001), but APN+STZ was able to enhance IRS-1 expression rate (P≤0.0001).CONCLUSION:In a rat model of AD, we found that adiponectin improved aversive and cognitive memory, which is at least partially mediated by the mTOR signaling cascade.

Glioblastoma is the most common primary malignant brain tumor in adults.Temozolomide (TMZ) is an FDAapproved drug used to treat this type of cancer.Cinnamaldehyde (CIN) is a derivative of cinnamon extract and makes up 99% of it.The aim of this study was to investigate the in vitro combined effect of CIN and TMZ on human glioblastoma multiforme T98G cell line viability.In this study, we used 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl-tertazolium bromide (MTT) method to evaluate the extent of IC 50 , acridine orange, Giemsa and Hoechst staining to evaluate the manner of apoptosis and the Western blotting method to examine the expression change of apoptotic proteins.Our results show that TMZ has an inhibitory effect on CIN when both used in combination at concentrations of 300 and 100 μM (P<0.05) and has a cytotoxic effect when used alone at the same concentrations (P<0.05).The western blotting result showed that TMZ at concentrations of 2,000 and 1,000 μM significantly increased Bax expression and decreased Bcl2 expression (P<0.05),indicating that TMZ induced apoptosis through the mitochondrial pathway.However, CIN had no effect on Bax and Bcl2 expressions, thus causing apoptosis from another pathway.Also, the Bax:Bcl2 expression ratio at concentrations combined was lower than that for TMZ 1,000 μM and higher than that for CIN 150 and 100 μM (P<0.05), which confirms the inhibitory effect of TMZ on CIN.From the present study, we conclude that TMZ in combination with CIN has an inhibitory effect on increasing the cytotoxicity rate.

Depression is a series of symptoms that influence mood, thinking, and behavior and create unpleasant emotions like hopelessness and apathy. Treatment-resistant depression (TRD) affects 30 % of depression patients despite the availability of several non-invasive therapies. Deep brain stimulation (DBS) is a novel therapy for TRD. The aim of the current study was to evaluate the effect of LHb-DBS by recording local field potentials (LFP) and conducting behavioral experiments.Thirty-two mature male Wistar rats were randomly divided into four groups: control, chronic mild stress (CMS), CMS+DBS, and DBS. After surgery and electrode placement in the lateral habenula (LHb), nucleus accumbens (NAc), and prelimbic cortex (PrL), the CMS protocol was applied for 3 weeks to create depression-like models. The open field test (OFT), sucrose preference test (SPT), and forced swim test (FST) were also performed. In the DBS groups, the LHb area was stimulated for four consecutive days. Finally, on the 22nd day, LFP was recorded from the NAc and PrL and analyzed using MATLAB software. Analyzing the findings using ANOVA and P-values ≤ 0.05 was considered.LHb-DBS alleviated depression-like behaviors in chronic moderate stress model rats (P ≤ 0.05). Three weeks of CMS enhanced almost all band powers in the NAc, while LHb-DBS decreased the power of the theta, alpha, beta, and gamma bands in the NAc (P ≤ 0.05), and the low-gamma band in the PrL. CMS also boosted the NAc-PrL coherence in low-frequency bands, while LHb-DBS increased beta and low gamma band coherence (P ≤ 0.05).In sum, the results of the present study showed that depression enhances low-frequency coherence between NAc and PrL cortex. Depression also potentiates many brain oscillations in the NAc, which can be mainly reversed by LHb-DBS.

The hippocampal-prefrontal cortex network dynamics is reported to be involved in various cognitive functions and in different mood disturbances including depression. It has been suggested that blocking orexin-1 receptors can be beneficial in depression. The purpose of this study is to determine whether orexin-1 receptor antagonists have an impact on changes in brain oscillations in the hippocampus and prefrontal cortex in a rat model of depression. Forty-eight male Wistar rats were divided into six experimental groups: control, chronic mild stress (CMS), acute SB-334867, a selective orexin-1 receptor antagonist, treated rats (SB), chronic SB-treated (CSB), CMS+SB, and CMS+CSB. Two stainless steel recording electrodes were placed in the coordinates of the hippocampus (HPC) and the prefrontal cortex (PFC). After behavioral verification of the model, local field potentials were recorded at 1 kHz sampling frequency. The absolute power of different frequency bands was obtained using the Fast Fourier Transform (FFT) function, and the power spectral density (PSD) of each frequency band was calculated for each animal. In the CMS- treated animals, the low-gamma band power increased both in the HPC and PFC (p ≤ 0.05), which were reversed by chronic SB-334867 treatment (p ≤ 0.05). The alterations in theta, and high-gamma band power were not significant in CMS treated rats, while acute and chronic SB-334867 treatment diminished the theta and high-gamma band power (p ≤ 0.05), respectively. The hippocampal-prefrontal coherence decreased in the delta (p ≤ 0.01), theta (p ≤ 0.01), and alpha (p ≤ 0.05) band range of the CMS exposed rats. It is concluded that CMS boosts the low-gamma band power, which is reversed by CSB treatment. The low-frequency band coherence is attenuated after CMS treatment.

Depression is a devastating mood disorder affecting more than 300 million people worldwide. Almost 30 % of patients still suffer from treatment resistant depression. Although many reports support the involvement of orexin in the pathophysiology of depression, the precise role of orexin is still unclear. In this study, we evaluated the role of the orexin 1 receptor (Orx1R) on depressive behaviors and the alterations in postsynaptic density-95 (PSD-95) protein in the chronic mild stress (CMS) model of depression. Fifty-four male Wistar rats were randomly allocated to 6 groups; Control, CMS, acute SB-334867 (SB), CMS+SB, chronic SB (CSB) and CMS+CSB. Rats were exposed to one or two unpredictable stressors each day for three weeks for the induction of CMS. Intracerebroventricular (icv) injection of SB-334867, a selective Orx1R antagonist, was performed either 30 min before behavioral tests (acute) or once daily for 14 days (chronic). Behavioral despair was assessed by immobility time in the forced swim test (FST), sucrose consumption in sucrose preference test (SPT), and the number of crosses in the open field test (OFT) on days 1, 11, and 22 of the experiment. Finally, rats were decapitated, and brain tissue of the hippocampus (HPC) and prefrontal cortex (PFC) were collected, and the relative expression of PSD-95 was evaluated by western blotting. The CMS model rats showed a significant increase in FST immobility time (P = 0.001) and a decrease in locomotion (P = 0.04) and sucrose preference (P = 0.039). Chronic application of SB decreased immobility time to the control values (P = 0.001) and diminished locomotion (P = 0.047) and sucrose preference (P = 0.042) in comparison to the CMS group. Acute SB reversed just the immobility time (P ≤ 0.006). Chronic SB treatment increased the relative PSD-95 expression in PFC (P = 0.001). Hence, chronic antagonism of Orx1R alleviates depressive behaviors induced by CMS and improves PSD-95 expression in PFC.

Background and aim: Alzheimer's disease (AD), a prevalent progressive neurodegenerative disease, is mainly characterized by dementia, memory loss, and cognitive disorder. Rising research was performed to develop pharmacological or non-pharmacological approaches to treat or improve AD complications. Mesenchymal stem cells (MSCs) are stromal cells that can self-renew and exhibit multilineage differentiation. Recent evidence suggested that some of the therapeutic effects of MSCs are mediated by the secreted paracrine factors. These paracrine factors, called MSC-conditioned medium (MSC-CM), may stimulate endogenous repair, promote angio-and artery genesis, and reduce apoptosis through paracrine mechanisms. The current study aims to sys-tematically review the advantages of MSC-CM to the development of research and therapeutic concepts for AD management.Material and methods: The present systematic review was performed using PubMed, Web of Science, and Scopus from April 2020 to May 2022 following the "Preferred Reporting Items for Systematic Reviews" (PRISMA) guidelines. The keywords, including "Conditioned medium OR Conditioned media OR Stem cell therapy" AND "Alzheimer's," was searched, and finally, 13 papers were extracted.Results: The obtained data revealed that MSC-CMs might positively affect neurodegenerative diseases prognosis, especially AD, through various mechanisms, including a decrease in neuro-inflammation, reduction of oxidative stress and A & beta; formation, modulation of Microglia function and count, reduction of apoptosis, induction of synaptogenesis and neurogenesis. Also, the results showed that MSC-CM administration could significantly improve cognitive and memory function, increase the expression of neurotrophic factors, decrease the production of pro inflammatory cytokines, improve mitochondrial function, reduce cytotoxicity, and increase neurotransmitter levels.Conclusion: While inhibiting the induction of neuroinflammation could be considered the first therapeutic effect of CMs, the prevention of apoptosis could be regarded as the most crucial effect of CMs on AD improvement.

Photobiomodulation therapy has become the focus of medical research in many areas such as Alzheimer's disease (AD), because of its modulatory effect on cellular processes through light energy absorption via photoreceptors/chromophores located in the mitochondria. However, there are still many questions around the underlying mechanisms. This study was carried out to unravel whether the function-structure of ATP-sensitive mitoBKCa channels, as crucial components for maintenance of mitochondrial homeostasis, can be altered subsequent to light therapy in AD. Induction of Aβ neurotoxicity in male Wistar rats was done by intracerebroventricular injection of Aβ1-42. After a week, light-treated rats were exposed to 40-Hz white light LEDs, 15 min for 7 days. Electrophysiological properties of mitoBKCa channel were investigated using a channel incorporated into the bilayer lipid membrane, and mitoBKCa-β2 subunit expression was determined using western blot analysis in Aβ-induced toxicity and light-treated rats. Our results describe that conductance and open probability (Po) of mitoBKCa channel decreased significantly and was accompanied by a Po curve rightward shift in mitochondrial preparation in Aβ-induced toxicity rats. We also showed a significant reduction in expression of mitoBKCa-β2 subunit, which is partly responsible for a leftward shift in BKCa Po curve in low calcium status. Interestingly, we provided evidence of a significant improvement in channel conductance and Po after light therapy. We also found that light therapy improved mitoBKCa-β2 subunit expression, increasing it close to saline group. The current study explains a light therapy improvement in brain mitoBKCa channel function in the Aβ-induced neurotoxicity rat model, an effect that can be linked to increased expression of β2 subunit.

Abstract Background Glutamate neurotransmission stands as an important issue to minimize memory impairment. We investigated the effects of an inhibitor of α-amino-3-hydroxy-5-methyl-4-isozazole propionic acid receptors (AMPA) endocytosis and GluN2B subunit of N-methyl-d-aspartate receptors (NMDA), either isolated or combined, on memory impairments induced by Amyloid beta1-42 (Aβ). Methods Eighty male Wistar rats were used for two experiments of consolidation and retrieval of memory. Memory impairment was induced by intracerebroventricular (ICV) injection of Aβ1-42 (2 μg/μl), and evaluated using Morris Water Maze (MWM). Each experiment consisted of 5 groups: Saline + Saline, Aβ + Saline, Aβ + Ifenprodil (Ifen, 3 nmol/ICV), Aβ +Tat-GluR23Y (3 µmol/kg/IP), and Aβ1 +Ifen + Tat-GluR23Y. Then, hippocampal cAMP-response element-binding protein (CREB) was measured by western blotting. Data were analyzed by Analysis of variance (ANOVA) repeated measure, and one-way Anova followed by Tukey’s post hoc test. Results During retrieval, Aβ+ Tat-GluR23Y showed significant improvement in total time spent (TTS) in the target quadrant (p = 0.009), escape latency to a platform (p = 0.008) and hippocampal level of CREB (p = 0.006) compared with Aβ + saline. Also, coadministration of Tat-GluR23Yand Ifen similar to Tat-GluR23Y alone caused significant improvement in TTS (p = 0.014) and latency to platform (p = 0.013). During consolidation, shorter escape latency (p = 0.001), longer TTS (p = 0.002) and higher level of hippocampal CREB were observed in the Aβ + Tat-GluR23Y (p = 0.001) and Aβ+ Tat-GluR23Y + Ifen (p = 0.017), respectively. Conclusion The present study provides pieces of evidence that inhibition of AMPARs endocytosis using Tat-GluR23Y facilitates memory consolidation and retrieval in Aβ induced memory impairment via the CREB signaling pathway. Graphical abstract

Introduction: MicroRNAs are small, non-coding, and protected RNA molecules that regulate gene expression after transcription by mRNA degradation or inhibition of protein synthesis. The function of these molecules is critical to many cellular processes, including growth, development, differentiation, homeostasis, apoptosis, aging, stress resistance. In addition, some diseases including cancer, and neurodegenerative diseases such as Alzheimer's are associated with microRNA defects. microRNAs are highly stable in biological fluids, abundant in the brain, and regulate the processes involved in the onset and progression of Alzheimer's disease. Early detection of Alzheimer's as the most common dementia is not easily possible at present. By finding reliable and highly sensitive biomarkers, especially in the early stages of the disease, interventions will be performed at a better time to achieve a better clinical outcome. Thus, microRNAs have great potential as diagnostic and prognostic biomarkers. At the same time, modulating them could be a potential treatment strategy for Alzheimer's disease. The aim of this review is to describe microRNAs, their biogenesis, and their role in the pathogenesis of Alzheimer's disease and to investigate the importance of these molecules in the role of diagnostic biomarkers

Adiponectin (APN) plays a major role in the regulation of insulin sensitivity and glucose homeostasis. Insulin and APN have a positive effect on memory. In this study, we examined whether the inhibition of AMPK could block the memory improving effect of APN or affect the IRS1 expression. Animal model of AD was developed by intracerebroventricular (icv) injection of 3 mg/kg streptozotocin (STZ), in 12 weeks old Wistar rats, on days 1 and 3 after cannulation. Dorsomorphin (DM) and APN (600 nM) were injected 30 and 20 min before the acquisition phase, respectively. DM was applied in 3 different doses (0.2, 2 and 20 μM). All behavioral tests were performed on days 15 and 16; the Preference Index (PI) was calculated for novel object recognition (NOR) test, while the step through latency (STL) and total time in dark compartment (TDC) were recorded and analyzed for the passive avoidance task. Relative expression of insulin receptor substrate-1 (IRS-1) protein in the hippocampus was measured by western blotting. In early retrieval test, STZ + APN treatment increased STL (P < 0.0001) and decreased TDC (P < 0.05) in comparison to STZ group, while STZ + APN + DM (2μM) caused a decrease in STL (P < 0.05) and increase in TDC (0.2μM and 2μM DM; P < 0.05). Icv injection of DM (0.2μM and 2μM) before APN decreased the PI significantly (P < 0.05) in comparison to STZ + APN group. APN treatment raised the IRS-1 expression and DM reversed this increment, significantly (P < 0.0001). It is concluded that the memory improving effect of APN is mediated, at least in part, by the AMPK pathway. APN is also able to boost insulin signaling by overexpression of IRS-1 in the hippocampus.

The novel coronavirus, termed severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) is a major public health challenge all over the world and is the causative agent of coronavirus disease 2019 (COVID-19). Since December 2019 the outbreak of COVID-19 has become a major epidemic issue all over world. In this pandemic, preterm and term neonates with infected mothers are becoming more vulnerable each day. Although we mostly witness asymptomatic neonates, getting symptomatic may not be a rarity in the future. After entrance of COVID-19 into the body it could affect the balance of microbiota combination which can result in microbiota dysbiosis and eventually leads to immune imbalance. Intrauterine microbiome dysbiosis in COVID-19 positive mothers and transmission of lipopolysaccharide (LPS) may restructure the environment of the developing fetus with possible short/long-term impact on the individual's health and disease. Therefore, assessing the changes in microbiome of neonates from infected mothers via exploring meconium could be valuable. It is also logical to measure LPS level and balanced its levels by using prebiotics and probiotics as a supplemental therapeutic procedure to prevent medical challenges in future. The aim of this essay is to review the potential conception that detection of COVID-19 and the meconium microbiota and LPS quantity could be used as a source of prognostic information about the COVID-19 severity in the fetus of pregnant women with COVID-19.

Alzheimer’s disease (AD) is behaviorally characterized by memory impairments, and pathologically by amyloid β1–42 (Aβ1–42) plaques and tangles. Aβ binds to excitatory synapses and disrupts their transmission due to dysregulation of the glutamate receptors. Here we hypothesized that chronic inhibition of the endocytosis of AMPA receptors together with GluN2B subunit of NMDA receptors might improve cognition deficit induced by Aβ(1–42) neurotoxicity. Forty male Wistar rats were used in this study and divided into 5 groups: Saline + Saline, Aβ+Saline, Aβ+Ifen (Ifenprodil, 3 nmol /2 weeks), Aβ+GluR23Y (Tat-GluR23Y 3 μmol/kg/2 weeks) and Aβ+Ifen+GluR23Y (same doses and durations). Aβ(1–42) neurotoxicity was induced by intracerebroventricular (ICV) injection of Aβ1–42 (2 μg/μl/side), and then animals received the related treatments for 14 days. Cognitive performance of rats and hippocampal level of cAMP-response element-binding (CREB) were evaluated using Morris Water Maze (MWM), and western blotting respectively. Obtained data from the acquisition trials were analyzed by two way Anova and Student T test. Also one way Analysis of variance (ANOVA) with post hoc Tuckey were used to clarify between groups differences in probe test. The Group receiving Aβ, showed significant cognition deficit (long latency to platform and short total time spent in target quadrant (TTS), parallel with lower level of hippocampal CREB, versus vehicle group. While, Aβ+ GluR23Y exhibited the shortest latency to platform and the longest TTS during the probe test, parallel with the higher hippocampal level of CREB compared with other groups. The present study provides evidence that chronic administration of Tat-GluR23Y; an inhibitor of GluA2-AMPARs endocytosis, successfully restores spatial memory impaired by amyloid beta neurotoxicity targeting CREB signaling pathway.