2025
Pathological Calcium Signaling in Traumatic Brain Injury and Alzheimer’s Disease: From Acute Neuronal Injury to Chronic Neurodegeneration
Neuschmid S, Schallerer C, Ehrlich B, McGuone D. Pathological Calcium Signaling in Traumatic Brain Injury and Alzheimer’s Disease: From Acute Neuronal Injury to Chronic Neurodegeneration. International Journal Of Molecular Sciences 2025, 26: 9245. PMID: 41009808, PMCID: PMC12471116, DOI: 10.3390/ijms26189245.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseCalcium-dependent protease calpainPharmacological inhibitionCalcium signalingTau hyperphosphorylationAmyloid-bLoss of calcium homeostasisProtein misfoldingCalcium-dependent enzymesSignaling proteinsAD riskProtease calpainAD modelProtease networkDisrupted calcium signalingTraumatic brain injuryUpstream driversEnzyme activityPathological calcium signalingSynaptic architectureCalcium dysregulationAxonal transportNeuronal deathEssential scaffoldsCalcium homeostasisEngineering human neuronal diversity: Morphogens and stem cell technologies for neurodevelopmental biology
Scuderi S, Khouri-Farah N, Rauthan R, Natu A, Wang H, Nelson A, Jourdon A, Vaccarino F. Engineering human neuronal diversity: Morphogens and stem cell technologies for neurodevelopmental biology. Stem Cell Reports 2025, 20: 102615. PMID: 40930068, PMCID: PMC12447334, DOI: 10.1016/j.stemcr.2025.102615.Peer-Reviewed Original ResearchConceptsNeural tube patterningStem cell technologyTube patterningTranscription factor networksComplex assortmentFactor networksPluripotent stem cellsNeuronal cellsPatterns in vivoCell technologyProgenitor cellsEmbryonic tissuesNeurodevelopmental biologyBrain-on-chipNeuropsychiatric disordersHuman brain developmentStem cellsBrain developmentCellsBrain organoidsPatterning processMorphogenTranscriptionBrainStemA single-cell, long-read, isoform-resolved case-control study of FTD reveals cell-type-specific and broad splicing dysregulation in human brain
Belchikov N, Hu W, Fan L, Joglekar A, He Y, Foord C, Jarroux J, Hsu J, Pollard S, Amin S, Prjibelski A, Gong S, Zhang S, Giannelli R, Seelaar H, Tomescu A, Ross M, Li A, Grinberg L, Spina S, Miller B, Cooper-Knock J, Snyder M, Seeley W, Rao-Ruiz P, Spijker S, Smit A, Clelland C, Gan L, Tilgner H. A single-cell, long-read, isoform-resolved case-control study of FTD reveals cell-type-specific and broad splicing dysregulation in human brain. Cell Reports 2025, 44: 116198. PMID: 40913764, DOI: 10.1016/j.celrep.2025.116198.Peer-Reviewed Original ResearchConceptsSplicing patternsSplicing dysregulationCell typesHigh-interest genesCell type switchingTAR DNA-binding protein 43Single-cellDNA-binding protein 43Cell type-specificLong readsDysregulation eventsSplicingTDP-43Neuronal cellsFamilial FTDSequence 2ExonFrontotemporal dementiaProtein 43CellsCase-control studyDysregulationGenesAge-specific regulation of sociability by hypothalamic Agrp neurons
Iyilikci O, Kim L, Zimmer M, Bober J, Li Y, Pelts M, Santana G, Dietrich M. Age-specific regulation of sociability by hypothalamic Agrp neurons. Current Biology 2025, 35: 4522-4536.e6. PMID: 40907492, DOI: 10.1016/j.cub.2025.08.014.Peer-Reviewed Original ResearchConceptsSocial behaviorAgRP neuronsNeuronal activityRegulation of sociabilitySocial isolationHypothalamic AgRP neuronsNeural mechanismsIntact olfactionAgRP neuron activityAge-specific regulationIn adulthoodRat pupsSociabilityArcuate nucleusAdolescentsYoung miceAgRPAdulthoodHomeostatic regulationNeuronsHomeostatic mechanismsAdult malesAdultsDevelopmental stagesIsolatesGenerative emergence of non-local representations in the hippocampus
Zhou Y, Sibille J, Dragoi G. Generative emergence of non-local representations in the hippocampus. Nature Communications 2025, 16: 8012. PMID: 40866358, PMCID: PMC12391462, DOI: 10.1038/s41467-025-63346-w.Peer-Reviewed Original ResearchComment on the Editorial “Embracing the Modern Biochemistry of Brain Metabolism”
Dienel G, Rothman D, Mangia S. Comment on the Editorial “Embracing the Modern Biochemistry of Brain Metabolism”. Journal Of Neurochemistry 2025, 169: e70197. PMID: 40810250, PMCID: PMC12351431, DOI: 10.1111/jnc.70197.Peer-Reviewed Original ResearchUCP2 mediates mitochondrial dynamics to induce AgRP neuronal activity
Jin S, Yoon N, Liu Z, Menale C, Kim J, Diano N, Diano S. UCP2 mediates mitochondrial dynamics to induce AgRP neuronal activity. Molecular Metabolism 2025, 99: 102215. PMID: 40683468, PMCID: PMC12328681, DOI: 10.1016/j.molmet.2025.102215.Peer-Reviewed Original ResearchConceptsDynamin-related protein 1Mitochondrial dynamicsAgRP neuron activityExpression level of uncoupling protein 2AgRP neuronsFeeding behaviorWhole-body energy homeostasisLevel of uncoupling protein 2AgRP neuronal functionMitochondrial fatty acid utilizationMRNA expression levelsWhole-body energy metabolismMitochondrial proteinsMitochondrial fissionMitochondrial morphologyFatty acid oxidationAgouti-related protein (AgRP)-expressing neuronsNeuronal activityFatty acid utilizationHypothalamic AgRP neuronsAcid utilizationEnergy homeostasisUCP2Fasting-induced food intakeEnergy metabolismGlycogen supports glycolytic plasticity in neurons
Singh M, Wolfe A, Vishwanath A, Tsives A, Gonzalez I, Emerson S, Goodman R, Colón-Ramos D. Glycogen supports glycolytic plasticity in neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2509003122. PMID: 40638090, PMCID: PMC12280961, DOI: 10.1073/pnas.2509003122.Peer-Reviewed Original ResearchConceptsCaenorhabditis elegans</i>Conditions of mitochondrial dysfunctionCells of living animalsSynaptic vesicle recyclingTransient hypoxiaSingle cellsVesicle recyclingRNAi screenAssociated with defectsMitochondrial functionResponse to activationGlycolytic stateMitochondrial dysfunctionEnergy metabolism in vivoMetabolism in vivoSynaptic functionNeuronsIn vivoHypoxiaEnergy reservesGlycogen phosphorylaseGlycogenOrthologsCaenorhabditisMutantsTriglycerides are an important fuel reserve for synapse function in the brain
Kumar M, Wu Y, Knapp J, Pontius C, Park D, Witte R, McAllister R, Gupta K, Rajagopalan K, De Camilli P, Ryan T. Triglycerides are an important fuel reserve for synapse function in the brain. Nature Metabolism 2025, 7: 1392-1403. PMID: 40595405, PMCID: PMC12286841, DOI: 10.1038/s42255-025-01321-x.Peer-Reviewed Original ResearchConceptsLipid dropletsFatty acidsMitochondrial ATP productionFunction in vivoActivity-dependent fashionNerve terminalsATP productionNeuronal function in vivoSynapse functionAdult male miceTriglyceride lipaseIn vivo neuronsDDHD2Neuronal bioenergeticsMale miceAcute blockElectrical silenceMetabolic supportNeuronsNerveFuel reservesElectrical activityMitochondriaCognitive functionBioenergeticsNeurons exploit stochastic growth to rapidly and economically build dense dendritic arbors
Ouyang X, Sutradhar S, Trottier O, Shree S, Yu Q, Tu Y, Howard J. Neurons exploit stochastic growth to rapidly and economically build dense dendritic arbors. Nature Communications 2025, 16: 5903. PMID: 40593546, PMCID: PMC12217211, DOI: 10.1038/s41467-025-60800-7.Peer-Reviewed Original ResearchMapping of neurovascular and neurometabolic couplings by multimodal optical imaging
Herman P, Sanggaard S, James S, Akif A, Mishra S, Sanganahalli B, Verhagen J, Blumenfeld H, Hyder F. Mapping of neurovascular and neurometabolic couplings by multimodal optical imaging. Cerebral Cortex 2025, 35: bhaf165. PMID: 40624899, DOI: 10.1093/cercor/bhaf165.Peer-Reviewed Original ResearchConceptsCerebral blood volumeNeuronal activityNeurometabolic couplingAlterations of neuronal activityNeurovascular couplingImaging of metabolic activityCerebral blood volume changesBolus injectionGlucose uptakeMultimodal optical imagingBlood volumeCalcium indicatorNear-infrared spectroscopyOptical imagingSimultaneous imagingBlood volume changesNear-infrared spectroscopy recordingsTraumatic brain injuryBrain injuryMultiplexed optical imagingGlucose analogMetabolic activityGECIsOptical systemCa2Mitofusin 2 controls mitochondrial and synaptic dynamics of suprachiasmatic VIP neurons and related circadian rhythms
Stoiljkovic M, Song J, Hong H, Endle H, Varela L, Catarino J, Gao X, Liu Z, Sotonyi P, Diano S, Cedernaes J, Bass J, Horvath T. Mitofusin 2 controls mitochondrial and synaptic dynamics of suprachiasmatic VIP neurons and related circadian rhythms. Journal Of Clinical Investigation 2025, 135: e185000. PMID: 40590229, PMCID: PMC12208536, DOI: 10.1172/jci185000.Peer-Reviewed Original ResearchConceptsMitochondrial dynamicsMitofusin 2Perturb mitochondrial dynamicsDaily biological rhythmsEnvironmental cuesCellular adaptationMammalian organismsCircadian oscillatorVIP neuronsConditional ablationMitochondriaLD cycleCircadian rhythmicityLight/darkAdvanced phase angleCircadian rhythmSynaptic input organizationMitofusinBiological rhythmsMfn2OrganizationInput organizationNeuronsCore body temperatureSynaptic dynamicsHigher dopamine D1 receptor expression in prefrontal parvalbumin neurons underlies higher distractibility in marmosets versus macaques
Joyce M, Ivanov T, Krienen F, Mitchell J, Ma S, Inoue W, Nandy A, Datta D, Duque A, Arellano J, Gupta R, Gonzalez-Burgos G, Lewis D, Sestan N, McCarroll S, Martinez-Trujillo J, Froudist-Walsh S, Arnsten A. Higher dopamine D1 receptor expression in prefrontal parvalbumin neurons underlies higher distractibility in marmosets versus macaques. Communications Biology 2025, 8: 974. PMID: 40594842, PMCID: PMC12214923, DOI: 10.1038/s42003-025-08297-0.Peer-Reviewed Original ResearchConceptsLevels of dopamine D1 receptorDopamine D1 receptor-expressingPV neuronsD1 receptor expressionDopamine D1 receptorsDorsolateral prefrontal cortexModels of cognitionPrefrontal cortexD1 receptorsDistractor resistanceD1R expressionDopaminergic modulationSalient stimuliVisual fixation taskHigh distractionSustained attentionCognitive tasksCognitive performanceInhibitory parvalbuminFunctional microcircuitryPrimate modelDLPFCParvalbumin neuronsFixation taskD1RDorsal raphe nucleus MC4R-GABAergic neurons regulate feeding and anxiety
Yamagata S, Copperi F, White G, Kim J, Diano S. Dorsal raphe nucleus MC4R-GABAergic neurons regulate feeding and anxiety. Molecular Metabolism 2025, 99: 102199. PMID: 40602716, PMCID: PMC12275976, DOI: 10.1016/j.molmet.2025.102199.Peer-Reviewed Original ResearchConceptsDorsal raphe nucleusAnxiety-like behaviorDorsal raphe nucleus serotonin neuronsDorsal raphe nucleus neuronsWhole-body metabolismGlutamatergic populationsNeuronal populationsARC POMC neuronsCNS regulationSerotonin neuronsRaphe nucleusChemogenetic manipulationChemogenetic activationVGluT2 neuronsBrain areasMelanocortin receptor 4Paraventricular nucleusHypothalamic PVNSerotonin stainingPOMC neuronsArcuate nucleusSolitary tractMC4R neuronsNeuronal subpopulationsMetabolic regulationVisualizing nuclear pore complex plasticity with pan-expansion microscopy
Morgan K, Carley E, Coyne A, Rothstein J, Lusk C, King M. Visualizing nuclear pore complex plasticity with pan-expansion microscopy. Journal Of Cell Biology 2025, 224: e202409120. PMID: 40504117, PMCID: PMC12162248, DOI: 10.1083/jcb.202409120.Peer-Reviewed Original ResearchNeuronal ALKAL2 and its ALK receptor contribute to the development of colitis-associated colorectal cancer
Delanne-Cuménal M, Defaye M, Delanne-Cuménal A, Ahmed M, Ho V, Abdullah N, Alhassoun M, Svendsen K, Mager L, Schlessinger J, Hirota S, Altier C. Neuronal ALKAL2 and its ALK receptor contribute to the development of colitis-associated colorectal cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2500632122. PMID: 40493183, PMCID: PMC12184428, DOI: 10.1073/pnas.2500632122.Peer-Reviewed Original ResearchConceptsColitis-associated colorectal cancerAnaplastic lymphoma kinaseColorectal cancerAnaplastic lymphoma kinase activityColitis-associated colorectal cancer progressionAnaplastic lymphoma kinase receptorTRPV1+ nociceptorsDevelopment of colitis-associated colorectal cancerMouse colonic organoidsALK signalingInflammatory painTumor burdenTreatment resistanceSensory neuronsTumor growthColonic organoidsALKAL2Colonic mucosaOverall inflammationCancer progressionCancerIn vivoTRPV1NeuronsInflammationHeterozygosity for neurodevelopmental disorder-associated TRIO variants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice
Ishchenko Y, Jeng A, Feng S, Nottoli T, Manriquez-Rodriguez C, Nguyen K, Carrizales M, Vitarelli M, Corcoran E, Greer C, Myers S, Koleske A. Heterozygosity for neurodevelopmental disorder-associated TRIO variants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice. ELife 2025, 13: rp103620. PMID: 40488445, PMCID: PMC12148328, DOI: 10.7554/elife.103620.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderGuanine nucleotide exchange factorNeurodevelopmental disordersPresynaptic glutamate releaseLayer 5 pyramidal neuronsAssociated with neurodevelopmental disordersIntellectual disabilitySpectrum disorderMouse behaviorCognitive behaviorNucleotide exchange factorNeuronal developmentBrain developmentGlutamate releaseIncreased Rac1 activityBrain sizeSynaptic functionControlling neuronal developmentSchizophreniaImpaired abilityAssociated with increased levelsNeurodevelopmental eventsActive GTPaseGEF Tiam1Exchange factorA Bird's‐Eye View of Glycolytic Upregulation in Activated Brain: The Major Fate of Lactate Is Release From Activated Tissue, Not Shuttling to Nearby Neurons
Dienel G, Rothman D, Mangia S. A Bird's‐Eye View of Glycolytic Upregulation in Activated Brain: The Major Fate of Lactate Is Release From Activated Tissue, Not Shuttling to Nearby Neurons. Journal Of Neurochemistry 2025, 169: e70111. PMID: 40476345, PMCID: PMC12142580, DOI: 10.1111/jnc.70111.Peer-Reviewed Original ResearchConceptsNeuron-astrocyte interactionsCerebral blood flowMetabolic brain imagingMetabolite of glucoseMetabolic mismatchBlood-borne glucoseActive neuronsAdequate oxygenationNearby neuronsActive tissuesLactate transportBlood flowAerobic glycolysisGlycolytic metabolismIntense sensory stimulationAstrocytesNeuronsTissue pHBrain cellsAstrocytic glycogenBrainSensory stimulationTissueGlycolysisRate of glucoseNeuronal potassium channel activity triggers initiation of mRNA translation through binding of translation regulators
Malone T, Wu J, Zhang Y, Licznerski P, Chen R, Nahiyan S, Pedram M, Jonas E, Kaczmarek L. Neuronal potassium channel activity triggers initiation of mRNA translation through binding of translation regulators. Science Advances 2025, 11: eadv3140. PMID: 40435242, PMCID: PMC12118559, DOI: 10.1126/sciadv.adv3140.Peer-Reviewed Original ResearchConceptsMRNA translationTranslational regulationInitiation of mRNA translationInitiation of translationSevere intellectual disabilityRegulation of translationMRNA translation regulationNeurites of cortical neuronsB-actinChannel activityIntellectual disabilityPotassium channel activityNeuronal activityMolecular mechanismsInhibit initiationMutationsCell linesPharmacological stimulationCortical neuronsMRNABindingRegulationTranslationEIF4ECYFIP1Proliferative arrest induces neuronal differentiation and innate immune responses in normal and Creutzfeldt-Jakob Disease agent (CJ) infected rat septal neurons
Pagano N, Perez G, Garcia-Milian R, Manuelidis L. Proliferative arrest induces neuronal differentiation and innate immune responses in normal and Creutzfeldt-Jakob Disease agent (CJ) infected rat septal neurons. PLOS ONE 2025, 20: e0323825. PMID: 40434970, PMCID: PMC12118874, DOI: 10.1371/journal.pone.0323825.Peer-Reviewed Original ResearchConceptsSeptal neuronsInnate immune responseDifferential transcriptionCreutzfeldt-Jakob disease agentCJ infectionImmune responseBind misfolded proteinsInnate immune genesIntestinal myeloid cellsRat septal neuronsArrests normal cellsDisease agentsInnate immune transcriptsCreutzfeldt-JakobModel of latent infectionAnti-viral responseCDNA libraryUnique transcriptsPeripheral human bloodLate-onset diseaseUninfected neuronsUpregulated interferonImmune genesMyeloid cellsTranscription
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