The International Journal of Neuropsychopharmacology, Год журнала: 2024, Номер 27(10)
Опубликована: Окт. 1, 2024
Abstract Background Altered brain energy metabolism is implicated in Alzheimer disease (AD). Limited and conflicting studies on pH changes, indicative of metabolic alterations associated with neural activity, warrant a comprehensive investigation into their relevance this neurodegenerative condition. Furthermore, the relationship between these changes established AD neuropathological evaluations, such as Braak staging, remains unexplored. Methods We conducted quantitative meta-analyses postmortem cerebrospinal fluid patients non-AD controls using publicly available demographic data. collected raw data from NCBI GEO, PubMed, Google Scholar databases. Results Our analysis 20 datasets (723 patient samples 524 control samples) random-effects model showed significant decrease compared (Hedges’ g = −0.57, P < .0001). This remained after considering interval, age at death, sex. Notably, levels were negatively correlated stage, indicated by correlation coefficients 15 (292 159 (adjusted r −0.26, enhanced discriminative power APOEε4 allele, most prevalent risk gene for AD, distinguishing meta-analysis 4 combined (95 87 samples). Conclusions The underlines its potential role progression diagnosis. decrease, potentially reflecting hyperexcitation, could enhance our understanding pathology aid developing diagnostic strategies.
Язык: Английский
Процитировано
5Gene Expression Signatures of Immaturity, Decreased
Neuropsychopharmacology Reports, Год журнала: 2025, Номер 45(1)
Опубликована: Фев. 5, 2025
ABSTRACT Aims Alzheimer's disease (AD) is a leading cause of dementia, with increasing prevalence. Mutations in genes like MAPT, PSEN1, and PSEN2 are risk factors, to the development several AD model mice. Recent hypotheses suggest brain pathology involves abnormal neurodevelopment, decreased pH, neural hyperexcitation. However, it remains unclear what extent these pathologies reflected gene expression changes models. This study aims compare patterns brains multiple mice those related three evaluating overlap. Methods We conducted comprehensive search public databases, collecting 20 datasets from hippocampus These were compared sets hippocampal maturation, hyperexcitation statistically assess Pathway enrichment analysis explored biological relevance changes. Results The overlap maturity‐, pH‐, hyperexcitation‐associated varied across models, showing significant correlations between lower maturity, increased In MAPT mutant APP+PSEN1 homozygous transgenic mice, signatures became more pronounced age. meta‐analysis revealed that associated models involved synaptic channel functions, as well inflammatory responses, consistent previous studies. Conclusion findings pathophysiological play varying roles individual Our recent found negative correlation progression actual pH levels human patients. Considering results presented this study, maturity hyperexcitation, which correlated may also be linked progression. Thus, factors could useful markers for assessing
Язык: Английский
Процитировано
0Cell Type-Specific Contributions to Impaired Blood-Brain Barrier and Cerebral Metabolism in Presymptomatic 5XFAD Mice
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
0Altered neuronal lactate dehydrogenase A expression affects cognition in a sex- and age-dependent manner
iScience, Год журнала: 2024, Номер 27(7), С. 110342 - 110342
Опубликована: Июнь 21, 2024
The astrocyte-neuron lactate shuttle (ANLS) model posits that astrocyte-generated is transported to neurons fuel memory processes. However, express high levels of dehydrogenase A (LDHA), the rate-limiting enzyme production, suggesting a cognitive role for neuronally generated lactate. It was hypothesized metabolism in critical learning and memory. Here transgenic mice were conditionally induce or knockout (KO)
Язык: Английский
Процитировано
2Metabolic Insights into Neuropsychiatric Illnesses and Ketogenic Therapies: A Transcriptomic View
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(15), С. 8266 - 8266
Опубликована: Июль 29, 2024
The disruption of brain energy metabolism, leading to alterations in synaptic signaling, neural circuitry, and neuroplasticity, has been implicated severe mental illnesses such as schizophrenia, bipolar disorder, major depressive disorder. therapeutic potential ketogenic interventions these disorders suggests a link between metabolic disturbances disease pathology; however, the precise mechanisms underlying disturbances, effects therapy, remain poorly understood. In this study, we conducted an silico analysis transcriptomic data investigate perturbations pathways across via gene expression profiling. We also examined dysregulation same rodent or cell culture models ketosis, comparing profiles those observed states. Our revealed significant all pathways, with greatest glycolysis, tricarboxylic acid (TCA) cycle, electron transport chain (ETC) three disorders. Additionally, some discordant patterns states intervention studies, suggesting role for ketone bodies modulating pathogenic changes. findings highlight importance understanding benefits restoring homeostasis. This study provides insights into complex relationship metabolism neuropsychiatric lays foundation further experimental investigations aimed at appreciating implications present well developing targeted strategies.
Язык: Английский
Процитировано
2Decreased brain pH correlated with progression of Alzheimer’s disease neuropathology: a systematic review and meta-analyses of postmortem studies
medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Май 2, 2024
Abstract Background Altered brain energy metabolism is implicated in Alzheimer’s disease (AD). Limited and conflicting studies on pH changes, indicative of metabolic alterations associated with neural activity, warrant a comprehensive investigation into their relevance this neurodegenerative condition. Furthermore, the relationship between these changes established AD neuropathological evaluations, such as Braak staging, remains unexplored. Methods We conducted quantitative meta-analyses postmortem cerebrospinal fluid patients non-AD controls, using publicly available demographic data. collected raw data from NCBI GEO, PubMed, Google Scholar databases. Results Our analysis 17 datasets (457 315 controls) random-effects model showed significant decrease compared to controls (Hedges’ g = –0.54, p < 0.0001). This remained after considering interval, age at death, sex. Notably, levels were negatively correlated stage, indicated by correlation coefficients 15 (292 159 (adjusted r –0.26, enhanced discriminative power APOE ε4 allele, most prevalent risk gene for AD, distinguishing meta-analysis four combined (95 87 controls). Conclusions The underlines its potential role progression diagnosis. decrease, potentially reflecting hyperexcitation, could enhance our understanding pathology aid developing diagnostic strategies.
Язык: Английский
Процитировано
1Elevated serum IGFBP-1 levels correlate with cognitive deficits in treatment-resistant and chronic medicated schizophrenia patients
Cytokine, Год журнала: 2024, Номер 182, С. 156728 - 156728
Опубликована: Авг. 9, 2024
Язык: Английский
Процитировано
1Postmortem evidence of decreased brain pH in major depressive disorder: a systematic review and meta-analysis
Translational Psychiatry, Год журнала: 2024, Номер 14(1)
Опубликована: Ноя. 4, 2024
Abstract Introduction Major depressive disorder (MDD) is a prevalent and debilitating mental that shares symptoms, genetics, molecular changes in the brain with other psychiatric disorders, such as schizophrenia bipolar disorder. Decreased pH, associated increased lactate levels due to altered energy metabolism neuronal hyperexcitation, has been consistently observed We recently demonstrated similar alterations various animal models of neuropsychiatric including MDD. However, our understanding pH human patients MDD remains limited. Methods conducted meta-analyses assess postmortem compared control subjects, examining its relationships recurrence episodes illness duration, utilizing publicly available demographic data. Studies reporting individual raw data were identified through searches Stanley Medical Research Institute database, NCBI GEO PubMed, Google Scholar. The analyzed using random effects model, ANOVA, ANCOVA. Results 39 curated datasets (790 957 controls), indicated significant decrease (Hedges’ g = −0.23, p 0.0056). A two-way ANCOVA revealed effect diagnosis on remained when considering covariates, interval, age at death, sex. Patients recurrent episodes, but not single episode, showed significantly lower than controls both females males (256 279 from seven datasets). Furthermore, negative correlation was between duration (115 five Female preponderance decreased also found, possibly longer higher tendency females. Conclusion This study suggests MDD, potentially duration. As suggested previous model studies, metabolism, leading may serve potential transdiagnostic endophenotype for disorders.
Язык: Английский
Процитировано
1Glu592 of the axon guidance receptor
FEBS Letters, Год журнала: 2024, Номер unknown
Опубликована: Ноя. 12, 2024
There are only a few studies on the function of neuronal axon guidance molecules during low brain pH conditions. We previously reported that roundabout (ROBO) 2, receptor for molecule SLIT, can bind to neural epidermal growth factor‐like‐like (NELL) ligands in acidic conditions by conformational change its ectodomain. Here, we show ROBO3 also exhibits pH‐dependent increase binding NELL2 ligand. found Glu592 residue at interface between and is sensor formation new hydrogen bonding network, due protonation Glu592, leads increased These results suggest NELL2–ROBO3 signaling could be regulated extracellular pH.
Язык: Английский
Процитировано
1Excitation-Dependent pKa Extends the Sensing Range of Fluorescence Lifetime pH Sensors
Sensors, Год журнала: 2024, Номер 24(23), С. 7531 - 7531
Опубликована: Ноя. 26, 2024
Biological activity is strongly dependent on pH, which fluctuates within a variety of neutral, alkaline, and acidic local environments. The heterogeneity tissue subcellular pH has driven the development sensors with different pKa values, huge assortment fluorescent have been created to measure visualize in living cells tissues. In particular, that report based fluorescence lifetime are advantageous for quantitation. Here, we apply theoretical framework derive how apparent lifetime-based depends excitation wavelength. We demonstrate theory predicts behavior two protein-based solution as proofs-of-concept. Furthermore, show this great practical value because it extends sensing range single sensor by simply choosing appropriate detection parameters match physiological interest. More broadly, our results versatility significantly underappreciated, approach provides means use across
Язык: Английский
Процитировано
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