Treatment Outcomes of Lip Taping in Patients with Non-syndromic Cleft Lip and/or Palate: A Systematic Review and Meta-analysis.

OBJECTIVE: To conduct a systematic review of the data in peer-reviewed medical literature and evaluate the effectiveness of lip taping as a pre-surgical naso-alveolar molding (NAM) technique in infants with cleft lip and/or palate. DESIGN: An electronic search of various databases for relevant studies, regardless of date, from inception to June 2023 was carried out and evaluated. After completing the electronic search and applying our inclusion/exclusion criteria, 6 studies-2 randomized control trials, 2 non-randomized studies, and 2 case series-were included. Data extraction of relevant articles was done independently by 2 authors. Quality assessment was done using the JBI prevalence critical appraisal tool and certainty of evidence was carried out by GRADE approach. MAIN OUTCOME MEASURES: Nasolabial Aesthetics, Dentoalveolar Relationship. RESULTS: A total of six studies were included in the current review. Meta-analysis was carried out, and forest plots were obtained for a single mean from the lip-taping group. 3 studies had a low risk of bias, while 3 studies displayed a serious risk of bias. Significant improvement in various outcome measures was noted with lip taping when compared with the control group although the certainty of evidence was very low. CONCLUSION: When compared to no therapy, lip taping appears to ameliorate dentoalveolar measurements and nasolabial aesthetics. To increase our knowledge of lip taping, more research will be needed in the future, as there are not many studies to prove lip taping is better than other treatment approaches.

Epigenetic age predictors in community-dwelling adults with high impact knee pain.

Gerontological research reveals considerable interindividual variability in aging phenotypes, and emerging evidence suggests that high impact chronic pain may be associated with various accelerated biological aging processes. In particular, epigenetic aging is a robust predictor of health-span and disability compared to chronological age alone. The current study aimed to determine whether several epigenetic aging biomarkers were associated with high impact chronic pain in middle to older age adults (44-78 years old). Participants (n = 213) underwent a blood draw, demographic, psychosocial, pain and functional assessments. We estimated five epigenetic clocks and calculated the difference between epigenetic age and chronological age, which has been previously reported to predict overall mortality risk, as well as included additional derived variables of epigenetic age previously associated with pain. There were significant differences across Pain Impact groups in three out of the five epigenetic clocks examined (DNAmAge, DNAmPhenoAge and DNAmGrimAge), indicating that pain-related disability during the past 6 months was associated with markers of epigenetic aging. Only DNAmPhenoAge and DNAmGrimAge were associated with higher knee pain intensity during the past 48 h. Finally, pain catastrophizing, depressive symptomatology and more neuropathic pain symptoms were significantly associated with an older epigenome in only one of the five epigenetic clocks (i.e. DNAmGrimAge) after correcting for multiple comparisons (corrected p's < 0.05). Given the scant literature in relation to epigenetic aging and the complex experience of pain, additional research is needed to understand whether epigenetic aging may help identify people with chronic pain at greater risk of functional decline and poorer health outcomes.

Hippocampal Subregion Transcriptomic Profiles Reflect Strategy Selection during Cognitive Aging.

Age-related cognitive impairments are associated with differentially expressed genes (DEGs) linked to defined neural systems; however, studies examining multiple regions of the hippocampus fail to find links between behavior and transcription in the dentate gyrus (DG). We hypothesized that use of a task requiring intact DG function would emphasize molecular signals in the DG associated with a decline in performance. We used a water maze beacon discrimination task to characterize young and middle-age male F344 rats, followed by a spatial reference memory probe trial test. Middle-age rats showed increased variability in discriminating two identical beacons. Use of an allocentric strategy and formation of a spatial reference memory were not different between age groups; however, older animals compensated for impaired beacon discrimination through greater reliance on spatial reference memory. mRNA sequencing of hippocampal subregions indicated DEGs in the DG of middle-age rats, linked to synaptic function and neurogenesis, correlated with beacon discrimination performance, suggesting that senescence of the DG underlies the impairment. Few genes correlated with spatial memory across age groups, with a greater number in region CA1. Age-related CA1 DEGs, correlated with spatial memory, were linked to regulation of neural activity. These results indicate that the beacon task is sensitive to impairment in middle age, and distinct gene profiles are observed in neural circuits that underlie beacon discrimination performance and allocentric memory. The use of different strategies in older animals and associated transcriptional profiles could provide an animal model for examining cognitive reserve and neural compensation of aging.SIGNIFICANCE STATEMENT Hippocampal subregions are thought to differentially contribute to memory. We took advantage of age-related variability in performance on a water maze beacon task and next-generation sequencing to test the hypothesis that aging of the dentate gyrus is linked to impaired beacon discrimination and compensatory use of allocentric memory. The dentate gyrus expressed synaptic function and neurogenesis genes correlated with beacon discrimination in middle-age animals. Spatial reference memory was associated with CA1 transcriptional correlates linked to regulation of neural activity and use of an allocentric strategy. This is the first study examining transcriptomes of multiple hippocampal subregions to link age-related impairments associated with discrimination of feature overlap and alternate response strategies to gene expression in specific hippocampal subregions.

Optimum multi-drug regime for compartment model of tumour: cell-cycle-specific dynamics in the presence of resistance.

This work is focused on multi-objective optimisation of a multi-drug chemotherapy schedule for cell-cycle-specific cancer treatment under the influence of drug resistance. The acquired drug resistance to chemotherapeutic agents is incorporated into the existing compartmental model of breast cancer. Furthermore, the toxic effect of drugs on healthy cells and overall drug concentration in the patient body are also constrained in the proposed model. The objective is to determine the optimal drug schedule according to the patient's physiological condition so that the tumour burden is minimised. A multi-objective optimisation algorithm, non-dominated sorting genetic algorithm-II (NSGA-II) is utilised to solve the problem. The obtained results are thoroughly analysed to illustrate the impact of drug resistance on the treatment. The capability of optimised schedules to deal with parametric uncertainty is also analysed. The drug schedules obtained in this work align well with the clinical standards. It is also revealed that the NSGA-II optimised drug schedule with proper rest period between successive dosages yields the minimum cancer load at the end of the treatment.

Enrichment of genomic pathways based on differential DNA methylation profiles associated with chronic musculoskeletal pain in older adults: An exploratory study.

Our study aimed to identify differentially methylated CpGs/regions and their enriched genomic pathways associated with underlying chronic musculoskeletal pain in older individuals. We recruited cognitively healthy older adults with (n = 20) and without (n = 9) self-reported musculoskeletal pain and collected DNA from peripheral blood that was analyzed using MethylationEPIC arrays. We identified 31,739 hypermethylated CpG and 10,811 hypomethylated CpG probes (ps ≤ 0.05). All CpG probes were clustered into 5966 regions, among which 600 regions were differentially methylated at p ≤ 0.05 level, including 294 hypermethylated regions and 306 hypomethylated regions (differentially methylated regions). Ingenuity pathway enrichment analysis revealed that the pain-related differentially methylated regions were enriched across multiple pathways. The top 10 canonical pathways were linked to cellular signaling processes related to immune responses (i.e. antigen presentation, programed cell death 1 receptor/PD-1 ligand 1, interleukin-4, OX40 signaling, T cell exhaustion, and apoptosis) and gamma-aminobutyric acid receptor signaling. Further, Weighted Gene Correlation Network Analysis revealed a comethylation network module in the pain group that was not preserved in the control group, where the hub gene was the cyclic adenosine monophosphate-dependent transcription factor ATF-2. Our preliminary findings provide new epigenetic insights into the role of aberrant immune signaling in musculoskeletal pain in older adults while further supporting involvement of dysfunctional GABAergic signaling mechanisms in chronic pain. Our findings need to be urgently replicated in larger cohorts as they may serve as a basis for developing and targeting future interventions.

Reliable anatase-titania nanoclusters functionalized GaN sensor devices for UV assisted NO2 gas-sensing in ppb level.

Internet of Things applications require ultra-low power, integrable into electronic circuits and mini-sized chemical sensors for automated remote air quality monitoring system. In this work, a highly sensitive and selective detection of nitrogen dioxide (NO2) has been demonstrated by functionalizing gallium nitride (GaN) submicron wire with titania (TiO2) nanoclusters. The two-terminal GaN/TiO2 sensor device was fabricated by top-down approach. The photo-enabled sensing makes it possible to operate this sensor at room-temperature, resulting in a significant reduction in operating power. The GaN/TiO2 sensor was able to detect NO2 concentrations as low as 10 ppb in air at room temperature (20 °C) with a quick response-recovery process. The sensor was found highly selective toward NO2 against other interfering gases, such as ethanol (C2H5OH), ammonia (NH3), sulfur dioxide (SO2), methane (CH4) and carbon dioxide (CO2). Furthermore, principal component analysis has been performed to address the cross-sensitive nature of TiO2. The sensor device exhibited excellent long-term stability at room temperature and humidity and was quite stable and reliable at various environmental conditions. Continuous exposure of the device to siloxane for a one-month period has shown a very small degradation in sensor response to NO2. Finally, interaction of NO2 gas molecules with the GaN/TiO2 sensor has been modeled and explained under the light of energy band diagram. The photoinduced oxygen desorption and subsequent charge transfer between TiO2 nanoclusters and NO2 molecules modulate the depletion region width within the GaN, thus contributing to a high performance NO2 gas sensing.

Tuning the Polarity of MoTe2 FETs by Varying the Channel Thickness for Gas-Sensing Applications.

In this study, electrical characteristics of MoTe2 field-effect transistors (FETs) are investigated as a function of channel thickness. The conductivity type in FETs, fabricated from exfoliated MoTe2 crystals, switched from p-type to ambipolar to n-type conduction with increasing MoTe2 channel thickness from 10.6 nm to 56.7 nm. This change in flake-thickness-dependent conducting behavior of MoTe2 FETs can be attributed to modulation of the Schottky barrier height and related bandgap alignment. Change in polarity as a function of channel thickness variation is also used for ammonia (NH3) sensing, which confirms the p- and n-type behavior of MoTe2 devices.

A Vegetable Fermentation Facility Hosts Distinct Microbiomes Reflecting the Production Environment.

Fermented vegetables are highly popular internationally in part due to their enhanced nutritional properties, cultural history, and desirable sensorial properties. In some instances, fermented foods provide a rich source of the beneficial microbial communities that could promote gastrointestinal health. The indigenous microbiota that colonize fermentation facilities may impact food quality, food safety, and spoilage risks and maintain the nutritive value of the product. Here, microbiomes within sauerkraut production facilities were profiled to characterize variance across surfaces and to determine the sources of these bacteria. Accordingly, we used high-throughput sequencing of the 16S rRNA gene in combination with whole-genome shotgun analyses to explore biogeographical patterns of microbial diversity and assembly within the production facility. Our results indicate that raw cabbage and vegetable handling surfaces exhibit more similar microbiomes relative to the fermentation room, processing area, and dry storage surfaces. We identified biomarker bacterial phyla and families that are likely to originate from the raw cabbage and vegetable handling surfaces. Raw cabbage was identified as the main source of bacteria to seed the facility, with human handling contributing a minor source of inoculation. Leuconostoc and Lactobacillaceae dominated all surfaces where spontaneous fermentation occurs, as these taxa are associated with the process. Wall, floor, ceiling, and barrel surfaces host unique microbial signatures. This study demonstrates that diverse bacterial communities are widely distributed within the production facility and that these communities assemble nonrandomly, depending on the surface type.IMPORTANCE Fermented vegetables play a major role in global food systems and are widely consumed by various global cultures. In this study, we investigated an industrial facility that produces spontaneous fermented sauerkraut without the aid of starter cultures. This provides a unique system to explore and track the origins of an "in-house" microbiome in an industrial environment. Raw vegetables and the surfaces on which they are handled were identified as the likely source of bacterial communities rather than human contamination. As fermented vegetables increase in popularity on a global scale, understanding their production environment may help maintain quality and safety goals.

Electronic Characteristics of MoSe2 and MoTe2 for Nanoelectronic Applications.

Single-crystalline MoSe2 and MoTe2 platelets were grown by Chemical Vapor Transport (CVT), followed by exfoliation, device fabrication, optical and electrical characterization. We observed that for the field-effect-transistor (FET) channel thickness in range of 5.5 nm to 8.5 nm, MoTe2 shows p-type, whereas MoSe2 with channel thickness range of 1.6 nm to 10.5 nm, shows n-type conductivity behavior. At room temperature, both MoSe2 and MoTe2 FETs have high ON/OFF current ratio and low contact resistance. Controlling charge carrier type and mobility in MoSe2 and MoTe2 layers can pave a way for utilizing these materials for heterojunction nanoelctronic devices with superior performance.

Re-Opening the Critical Window for Estrogen Therapy.

A decline in estradiol (E2)-mediated cognitive benefits denotes a critical window for the therapeutic effects of E2, but the mechanism for closing of the critical window is unknown. We hypothesized that upregulating the expression of estrogen receptor α (ERα) or estrogen receptor ß (ERß) in the hippocampus of aged animals would restore the therapeutic potential of E2 treatments and rejuvenate E2-induced hippocampal plasticity. Female rats (15 months) were ovariectomized, and, 14 weeks later, adeno-associated viral vectors were used to express ERα, ERß, or green fluorescent protein (GFP) in the CA1 region of the dorsal hippocampus. Animals were subsequently treated for 5 weeks with cyclic injections of 17ß-estradiol-3-benzoate (EB, 10 µg) or oil vehicle. Spatial memory was examined 48 h after EB/oil treatment. EB treatment in the GFP (GFP + EB) and ERß (ERß + EB) groups failed to improve episodic spatial memory relative to oil-treated animals, indicating closing of the critical window. Expression of ERß failed to improve cognition and was associated with a modest learning impairment. Cognitive benefits were specific to animals expressing ERα that received EB treatment (ERα + EB), such that memory was improved relative to ERα + oil and GFP + EB. Similarly, ERα + EB animals exhibited enhanced NMDAR-mediated synaptic transmission compared with the ERα + oil and GFP + EB groups. This is the first demonstration that the window for E2-mediated benefits on cognition and hippocampal E2 responsiveness can be reinstated by increased expression of ERα. SIGNIFICANCE STATEMENT: Estradiol is neuroprotective, promotes synaptic plasticity in the hippocampus, and protects against cognitive decline associated with aging and neurodegenerative diseases. However, animal models and clinical studies indicate a critical window for the therapeutic treatment such that the beneficial effects are lost with advanced age and/or with extended hormone deprivation. We used gene therapy to upregulate expression of the estrogen receptors ERα and ERß and demonstrate that the window for estradiol's beneficial effects on memory and hippocampal synaptic function can be reinstated by enhancing the expression of ERα. Our findings suggest that the activity of ERα controls the therapeutic window by regulating synaptic plasticity mechanisms involved in memory.

Analysis of the microbiome: Advantages of whole genome shotgun versus 16S amplicon sequencing.

The human microbiome has emerged as a major player in regulating human health and disease. Translational studies of the microbiome have the potential to indicate clinical applications such as fecal transplants and probiotics. However, one major issue is accurate identification of microbes constituting the microbiota. Studies of the microbiome have frequently utilized sequencing of the conserved 16S ribosomal RNA (rRNA) gene. We present a comparative study of an alternative approach using whole genome shotgun sequencing (WGS). In the present study, we analyzed the human fecal microbiome compiling a total of 194.1 × 10(6) reads from a single sample using multiple sequencing methods and platforms. Specifically, after establishing the reproducibility of our methods with extensive multiplexing, we compared: 1) The 16S rRNA amplicon versus the WGS method, 2) the Illumina HiSeq versus MiSeq platforms, 3) the analysis of reads versus de novo assembled contigs, and 4) the effect of shorter versus longer reads. Our study demonstrates that whole genome shotgun sequencing has multiple advantages compared with the 16S amplicon method including enhanced detection of bacterial species, increased detection of diversity and increased prediction of genes. In addition, increased length, either due to longer reads or the assembly of contigs, improved the accuracy of species detection.

α-Chymotrypsin regulates free fatty acids and UCHL-1 to ameliorate N-methyl nitrosourea induced mammary gland carcinoma in albino wistar rats.

This study was undertaken to investigate the effect of α-chymotrypsin on methyl nitrosourea (MNU) induced mammary gland carcinoma in albino wistar rats. Animals were randomized into four groups (six animals in each). Group I (sham control 0.9 % normal saline p.o.); Group II (toxic control, MNU 47 mg/kg, i.v.); Group III (α-chymotrypsin, 5 mg/kg, p.o.); Group IV (α-chymotrypsin, 10 mg/kg p.o.). Toxicity was induced by single i.v. injection of MNU followed by α-chymotrypsin supplementation therapy for 100 days. MNU treatment was evident with increased alveolar bud count, differentiation score, upregulated inflammatory enzymes markers (COX, LOX and NO) antioxidative stress markers (TBARs, SOD, catalase and GSH).MNU associated toxicity was also ascertained by PGP 9.5 and NF-κB expression in the mammary gland tissue followed by FAME analysis for fatty acid profiling. α-chymotrypsin afforded significant protection against the deleterious effects of MNU.

Performance Analysis of Fuzzy-PID Controller for Blood Glucose Regulation in Type-1 Diabetic Patients.

This paper presents Fuzzy-PID (FPID) control scheme for a blood glucose control of type 1 diabetic subjects. A new metaheuristic Cuckoo Search Algorithm (CSA) is utilized to optimize the gains of FPID controller. CSA provides fast convergence and is capable of handling global optimization of continuous nonlinear systems. The proposed controller is an amalgamation of fuzzy logic and optimization which may provide an efficient solution for complex problems like blood glucose control. The task is to maintain normal glucose levels in the shortest possible time with minimum insulin dose. The glucose control is achieved by tuning the PID (Proportional Integral Derivative) and FPID controller with the help of Genetic Algorithm and CSA for comparative analysis. The designed controllers are tested on Bergman minimal model to control the blood glucose level in the facets of parameter uncertainties, meal disturbances and sensor noise. The results reveal that the performance of CSA-FPID controller is superior as compared to other designed controllers.

Performance Evaluation and Implementation of FPGA Based SGSF in Smart Diagnostic Applications.

The main objective of the paper is to implement Savitzky Golay Smoothing Filter (SGSF) so as to apply in pre-processing of real time smart medical diagnostic systems. As very important information of EEG and ECG waveforms lies in the peak of the signal, hence it becomes absolutely necessary to filter noise and artifacts from the signal. The implemented filter should be able to reject the noise efficiently along with the least distortion from the original signal. The shape preserving characteristics of the filter are determined by introducing different noise levels in the signal. The designed filter is tested on synthetic signals of EEG and ECG by adding different types of noise and the performance is analysed on various parameters, i.e., SNR, SSNR, SNRI, MSE, COR and signal distortion of the final output. The smoothing performance comparison of SGSF with the most commonly used Moving Average Filter (MAF) proves that SGSF is more efficient. Hence it is suggested that MAF can be replaced by SGSF. For real time issues, it is further implemented on reconfigurable architectures so as to achieve high speed, low cost, low power consumption and less area. Therefore SGSF is realized on FPGA platform to combine the advantages of both. Real time EEG and ECG signals are also considered for experimentation. The experimental results show that the proposed methodology (FPGA-SGSF) significantly reduces the processing time and preserves the actual features of the signal.

Contribution of estrogen receptor subtypes, ERα, ERß, and GPER1 in rapid estradiol-mediated enhancement of hippocampal synaptic transmission in mice.

Estradiol rapidly modulates hippocampal synaptic plasticity and synaptic transmission; however, the contribution of the various estrogen receptors to rapid changes in synaptic function is unclear. This study examined the effect of estrogen receptor selective agonists on hippocampal synaptic transmission in slices obtained from 3-5-month-old wild type (WT), estrogen receptor alpha (ERαKO), and beta (ERßKO) knockout female ovariectomized mice. Hippocampal slices were prepared 10-16 days following ovariectomy and extracellular excitatory postsynaptic field potentials were recorded from CA3-CA1 synaptic contacts before and following application of 17ß-estradiol-3-benzoate (EB, 100 pM), the G-protein estrogen receptor 1 (GPER1) agonist G1 (100 nM), the ERα selective agonist propyl pyrazole triol (PPT, 100 nM), or the ERß selective agonist diarylpropionitrile (DPN, 1 µM). Across all groups, EB and G1 increased the synaptic response to a similar extent. Furthermore, prior G1 application occluded the EB-mediated enhancement of the synaptic response and the GPER1 antagonist, G15 (100 nM), inhibited the enhancement of the synaptic response induced by EB application. We confirmed that the ERα and ERß selective agonists (PPT and DPN) had effects on synaptic responses specific to animals that expressed the relevant receptor; however, PPT and DPN produced only a small increase in synaptic transmission relative to EB or the GPER1 agonist. We demonstrate that the increase in synaptic transmission is blocked by inhibition of extracellular signal-regulated kinase (ERK) activity. Furthermore, EB was able to increase ERK activity regardless of genotype. These results suggest that ERK activation and enhancement of synaptic transmission by EB involves multiple estrogen receptor subtypes.

Contribution of N-methyl-D-aspartate receptors to attention and episodic spatial memory during senescence.

A decrease in N-methyl-D-aspartate receptor (NMDAR) function is associated with age-related cognitive impairments. However, NMDAR antagonists are prescribed for cognitive decline associated with age-related neurodegenerative disease, raising questions as to the role of NMDAR activity in cognitive function during aging. The current studies examined effects of NMDAR blockade on cognitive task that are sensitive to aging. Young and middle-age rats were trained on the five-choice serial reaction time task (5-CSRTT) and challenged with MK-801 (0.025, 0.05, and 0.1mg/kg or vehicle). Attention deficits were apparent in middle-age and performance of young and middle-age rats was enhanced for low doses of MK-801 (0.025 and 0.05). The beneficial effects on attention were reversed by the highest dose of MK-801. Older animals exhibited a delay-dependent impairment of episodic spatial memory examined on a delayed-matching to place water maze task. Similarly, a low dose of MK-801 (0.05mg/kg) impaired performance with increasing delay and aged animals were more susceptible to disruption by NMDAR blockade. Despite MK-801 impairment of episodic spatial memory, MK-801 had minimal effects on spatial reference memory. Our results confirm that NMDARs contribute to rapidly acquired and flexible spatial memory and support the idea that a decline in NMDAR function contributes to the age-related impairments in cognition.

Some hormone, cytokine and chemokine levels that change across lifespan vary by cognitive status in male Fischer 344 rats.

We trained and tested young (6-8months; n=13), middle-aged (12-14months; n=41), and aged (22-24months; n=24) male Fischer 344 rats in a rapid acquisition water maze task and then quantified 27 stress hormones, cytokines and chemokines in their serum, hippocampi and frontal cortices using bead assay kits and xMAP technology. Middle-aged and aged rats learned the location of the hidden platform over training trials more slowly than their young counterparts. After training, young rats outperformed middle-aged and aged rats on both immediate and 24h retention probe trials and about half of the middle-aged and aged (aging) rats exhibited impaired performances when tested on the retention probe trial 24h later. The concentrations of many serum, hippocampal and cortical analytes changed with age often in networks that may represent age-sensitive signaling pathways and the concentrations of some of these analytes correlated with water maze learning and/or memory scores. Serum GRO/KC and RANTES levels, hippocampal GM-CSF levels and cortical IL-9 and RANTES levels were significantly higher in rats categorized as memory-impaired versus elite agers based upon their 24h probe trial performances. Our data add to the emerging picture of how age-related changes in immune and neuroimmune system signaling impacts cognition.

Role of estrogen receptor α and ß in preserving hippocampal function during aging.

The expression of the ERα and ERß estrogen receptors in the hippocampus may be important in the etiology of age-related cognitive decline. To examine the role of ERα and ERß in regulating transcription and learning, ovariectomized wild-type (WT) and ERα and ERß knockout (KO) mice were used. Hippocampal gene transcription in young ERαKO mice was similar to WT mice 6 h after a single estradiol treatment. In middle-age ERαKO mice, hormone deprivation was associated with a decrease in the expression of select genes associated with the blood-brain barrier; cyclic estradiol treatment increased transcription of these select genes and improved learning in these mice. In contrast to ERαKO mice, ERßKO mice exhibited a basal hippocampal gene profile similar to WT mice treated with estradiol and, in the absence of estradiol treatment, young and middle-age ERßKO mice exhibited preserved learning on the water maze. The preserved memory performance of middle-age ERßKO mice could be reversed by lentiviral delivery of ERß to the hippocampus. These results suggest that one function of ERß is to regulate ERα-mediated transcription in the hippocampus. This model is supported by our observations that knockout of ERß under conditions of low estradiol allowed ERα-mediated transcription. As estradiol levels increased in the absence of ERα, we observed that other mechanisms, likely including ERß, regulated transcription and maintained hippocampal-dependent memory. Thus, our results indicate that ERα and ERß interact with hormone levels to regulate transcription involved in maintaining hippocampal function during aging.

Serine racemase expression profile in the prefrontal cortex and hippocampal subregions during aging in male and female rats.

Aging is associated with a decrease in N-methyl-D-aspartate (NMDA) receptor function, which is critical for maintaining synaptic plasticity, learning, and memory. Activation of the NMDA receptor requires binding of the neurotransmitter glutamate and also the presence of co-agonist D-serine at the glycine site. The enzymatic conversion of L-serine to D-serine is facilitated by the enzyme serine racemase (SR). Subsequently, SR plays a pivotal role in regulating NMDA receptor activity, thereby impacting synaptic plasticity and memory processes in the central nervous system. As such, age-related changes in the expression of SR could contribute to decreased NMDA receptor function. However, age-associated changes in SR expression levels in the medial and lateral prefrontal cortex (mPFC, lPFC), and in the dorsal hippocampal subfields, CA1, CA3, and dentate gyrus (DG), have not been thoroughly elucidated. Therefore, the current studies were designed to determine the SR expression profile, including protein levels and mRNA, for these regions in aged and young male and female Fischer-344 rats. Our results demonstrate a significant reduction in SR expression levels in the mPFC and all hippocampal subfields of aged rats compared to young rats. No sex differences were observed in the expression of SR. These findings suggest that the decrease in SR levels may play a role in the age-associated reduction of NMDA receptor function in brain regions crucial for cognitive function and synaptic plasticity.