Sevoflurane Preconditioning Rescues PKMζ Gene Expression from Broad Hypoxia-Induced mRNA Downregulation Correlating with Improved Neuronal Recovery

NeuroSci, Год журнала: 2025, Номер 6(1), С. 9 - 9

Опубликована: Янв. 28, 2025

Hypoxia due to stroke is a major cause of neuronal damage, leading loss cognition and other brain functions. Sevoflurane preconditioning improves recovery after hypoxia. interferes with protein expression at the translational level; however, its effect on mRNA levels for kinase anti-apoptotic genes unclear. To investigate link between sevoflurane gene expression, hippocampal slices were treated 4% 15 min, 5 min washout, 10 hypoxia, 60 recovery. We used quantitative PCR measure in CA1 region rat hippocampi. The specific critical proteins examined, as follows: Protein kinases, PKCγ (0.22), PKCε (0.38), PKMζ (0.55) mRNAs, anti-apoptotic, bcl-2 (0.44) bcl-xl (0.41), reduced hypoxia relative their tissue not subjected (set 1.0). prevented reduction (0.88 vs. 1.0) Pro-apoptotic BAD was significantly changed even (hypoxia 0.81, sevo 0.84 normoxia However, increased by non-hypoxic conditions (1.48 1.0), which may partially explain deleterious effects volatile anesthetics under certain conditions. DNA repair enzyme poly ADP-ribose polymerase 1 (PARP-1) (1.23). PARP-1 untreated (0.21 1.0); did improve (0.27). Interestingly, level cognitive PKMζ, essential learning memory, only one protected against hypoxic downregulation preconditioning. These findings correlate previous studies that found sevoflurane-induced improvement survival dependent PKMζ. Maintaining provide an important mechanism preserving function stroke.

Язык: Английский

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Amygdala stimulation transforms short-term memory into remote memory by persistent activation of atypical protein kinase C in the anterior cingulate cortex

Neuroscience, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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Biophysically plausible models of synaptic plasticity

Elsevier eBooks, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Estimating and Augmenting Human-Systems Performance

NATO science for peace and security series. A, Chemistry and biology, Год журнала: 2025, Номер unknown, С. 1 - 24

Опубликована: Янв. 1, 2025

Язык: Английский

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Persistently increased expression of PKMzeta and unbiased gene expression profiles identify hippocampal molecular traces of a long-term active place avoidance memory and ′shadow′ proteins

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Май 2, 2025

Long-term memory formation transiently activates Ca2+-calmodulin kinase IIα (CaMKII) and atypical protein C isoform iota/lambda (PKC𝜄/λ), whereas persistent activation of the other PKC, M zeta (PKMζ), together with its interacting partner, scaffolding-protein KIBRA, is necessary for maintaining potentiated synapses memory. Here, we use immediate early gene (IEG) Arc during active place avoidance expression to tag memory-activated neurons EYFP, followed by PKMζ immunohistochemistry learn which hippocampal synaptic pathways are persistently altered. For at least 1 month, EYFP-PKMζ colocalization increase in tri-synaptic pathway (dentate gyrus (DG)→CA3→CA1). We thus DG, CA3, CA1 transcriptional profiling identify mRNAs molecules that might contribute find persistence correlates upregulation IEGs Arc, Fos, NPas4 DG. In contrast, CaMKII, PKMζ, PKC𝜄/λ, most LTP-associated proteins do not covary This result rules out strong memory-related regulation, but regulation mRNA translation or stability these ′shadow proteins′ that, despite being crucial maintenance, evade detection unbiased transcriptome profiling. further examine whether covarying defines molecular ensembles predict Prkcz expression. Community detection, applied both linear non-linear pairwise co-expression relationships, reveals networks predictive memory, IEGs, These findings trace: i) a engram hippocampus; highlight: ii) sustained >24-h maintenance; iii) utility investigating covariance patterns; iv) limits identifying long-term molecules, appear be ′shadow′ ; demonstrates v) weak pair-wise gene-gene correlations can related behavioral shadow estimates

Язык: Английский

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Windows of change: Revisiting temporal and molecular dynamics of memory reconsolidation and persistenc

Neuroscience & Biobehavioral Reviews, Год журнала: 2025, Номер unknown, С. 106198 - 106198

Опубликована: Май 1, 2025

Язык: Английский

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Persistent protein pairing enables memories to last

The Transmitter, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Язык: Английский

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Increased protein kinase Mζ expression by Minocycline and N-acetylcysteine restores late-phase long-term potentiation and spatial learning after closed head injury in mice

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 20, 2024

Abstract Cognitive deficits frequently arise after traumatic brain injury. The murine closed head injury (CHI) models these since injured mice cannot acquire Barnes maze. Dosing of minocycline plus N-acetylcysteine beginning 12 hours post-CHI (MN12) restores maze acquisition by an unknown mechanism. Increased hippocampal synaptic efficacy is needed to maze, long-term potentiation (LTP) this increased in vitro . LTP has early phase (E-LTP) lasting up one hour that mediated second messengers followed a late (L-LTP) needs new synthesis protein kinase M zeta (PKMζ). PKMζ constitutive activity because it lacks the autoinhibitory regulatory domain found other PKCs. Due its activity, amount determined levels. We report CHI bilaterally decreases levels CA3 and CA1 hippocampus. MN12 increases expression. inhibits E-LTP slices from ipsilesional hippocampus L-LTP both hippocamppi. treatment reestablishes MN12-treated restoration blocked specific inhibitor, ζ-stat. Hippocampal ζ-stat infusions also prevents injured, mice. These data suggest post-injury targets improve plasticity cognition with closed-head

Язык: Английский

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Maintenance of synaptic plasticity by negative-feedback of synaptic protein elimination: Dynamic modeling of KIBRA-PKMζ interactions in LTP and memory

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 27, 2024

Activity-dependent modifications of synaptic efficacies are a cellular substrate learning and memory. Current theories propose that the long-term maintenance memory is accomplished via positive-feedback loop at level production protein species or state. Here we qualitatively different theoretical framework based on negative-feedback elimination. This theory motivated by recent experimental findings regarding binding

Язык: Английский

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What are mechanisms? Unpacking the term is key to progress in neuroscience

The Transmitter, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Язык: Английский

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