Molecular and biophysical features of hippocampal “lipid rafts aging” are modified by dietary n‐3 long‐chain polyunsaturated fatty acids

Aging Cell, Journal Year: 2023, Volume and Issue: 22(8)

Published: May 30, 2023

Abstract “Lipid raft aging” in nerve cells represents an early event the development of aging‐related neurodegenerative diseases, such as Alzheimer's disease. Lipid rafts are key elements synaptic plasticity, and their modification with aging alters interactions distribution signaling molecules, glutamate receptors ion channels involved memory formation, eventually leading to cognitive decline. In present study, we have analyzed, vivo, effects dietary supplementation n‐3 LCPUFA on lipid structure, membrane microviscosity, domain organization, partitioning ionotropic metabotropic hippocampal raffs female mice. The results revealed several signatures “lipid old mice fed control diets, consisting depletion LCPUFA, unsaturation, along increased levels saturates, plasmalogens, sterol esters, well altered relevant indexes. These changes were paralleled by microviscosity raft/non‐raft (R/NR) AMPA‐R mGluR5. Administration diet caused partial reversion fatty acid alterations found aged returned values young animals. Paralleling these findings, accumulated mGluR5, NMDA‐R, ASIC2, R/NR proportions, which collectively indicate plasticity. Unexpectedly, this also modified lipidome dimension rafts, redistribution acid‐sensing likely modulating functionality formation reluctance age‐associated

Language: Английский

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Functional crosstalk of the glycine transporter GlyT1 and NMDA receptors

Neuropharmacology, Journal Year: 2023, Volume and Issue: 232, P. 109514 - 109514

Published: March 31, 2023

NMDA-type glutamate receptors (NMDARs) constitute one of the main (Glu) targets in central nervous system and are involved synaptic plasticity, which is molecular substrate learning memory. Hypofunction NMDARs has been associated with schizophrenia, while overstimulation causes neuronal death neurodegenerative diseases or stroke. The function requires coincidental binding Glu along other cellular signals such as depolarization, presence endogenous ligands that modulate their activity by allosterism. Among these allosteric modulators zinc, protons Gly, an obligatory co-agonist. These characteristics differentiate from receptors, structural bases have begun to be established recent years. In this review we focus on crosstalk between glycine (Gly), whose concentration NMDAR microenvironment maintained various Gly transporters remove release it into medium a regulated manner. GlyT1 transporter particularly task, become target great interest for treatment schizophrenia since its inhibition leads increase levels enhances NMDARs. However, only drug completed phase III clinical trials did not yield expected results. Notwithstanding, there additional drugs continue investigated, hoped knowledge gained recently published 3D structure may allow rational design more effective new drugs. This article part Special Issue "The receptor-receptor interaction therapy".

Language: Английский

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Synaptic Basis of Behavioral Timescale Plasticity

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 5, 2023

Abstract Learning and memory are fundamental to adaptive behavior cognition. Various forms of synaptic plasticity have been proposed as cellular substrates for the emergence feature selectivity in neurons underlying episodic memory. However, despite decades work, our understanding how underlies encoding remains limited, largely due a shortage tools technical challenges associated with visualization at single-neuron resolution awake-behaving animals. Behavioral Timescale Synaptic Plasticity (BTSP) postulates that inputs active during seconds-long time window preceding immediately following large depolarizing plateau spike potentiated, while outside this depressed. We experimentally tested model vivo mice using an all-optical approach by inducing place fields (PFs) single CA1 pyramidal (CA1PNs) monitoring spatiotemporal tuning individual dendritic spines changes their corresponding weights. identified asymmetric kernel resulting from bidirectional modifications weights around burst induction. Surprisingly, work also uncovered compartment-specific differences magnitude temporal expression between basal oblique dendrites CA1PNs. Our results provide first experimental evidence linking rapid spatial hippocampal neurons, critical prerequisite

Language: Английский

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SynBot is an open-source image analysis software for automated quantification of synapses

Cell Reports Methods, Journal Year: 2024, Volume and Issue: 4(9), P. 100861 - 100861

Published: Sept. 1, 2024

Language: Английский

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Hippocampal Lactate-Infusion Enhances Spatial Memory Correlated with Monocarboxylate Transporter 2 and Lactylation

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(4), P. 327 - 327

Published: March 28, 2024

Lactate has emerged as a key player in regulating neural functions and cognitive processes. Beyond its function an energy substrate signal molecule, recent research revealed lactate to serve epigenetic regulator the brain. However, molecular mechanisms by which regulates spatial memory role prevention of disorders remain unclear. Herein, we injected L-lactate (10 μmol/kg/d for 6 d) into mouse’s hippocampus, followed Morris water maze (MWM) test analyses. Improved performances were observed mice with lactate. Besides, upregulated expression synaptic proteins post-synaptic density 95 (PSD95), synaptophysin (SYP), growth associated protein 43 (GAP43) hippocampal tissues HT22 cells, suggesting potential transmission formation. The facilitative monocarboxylate transporter 2 (MCT2), neuron-specific transporter, this process was confirmed, MCT2 antagonists attenuated lactate-induced upregulation proteins. Moreover, induced lactylation, post-translational modification, could be suppressed inhibition. RNA sequencing lactated-injected comprehensive gene profile influenced lactate, significant changes genes transcriptional progress. These data demonstrate that injection enhances mice, potentially through induction playing crucial these Our findings shed light on multi-faceted regulation, opening new avenues therapeutic interventions targeting disorders.

Language: Английский

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