Brief mechanical pulses induce sustained intracellular L-lactate production in astrocytes

Belko Parkel, Kaja (author), Kuhanec, Danaja (author), Gržina, Živa Tajda (author), Chowdhury Haque, Helena (author), Zorec, Robert (author), Kreft, Marko (author)

Intracranial-pressure transients impose mechanical strain on perivascular astrocytes, but it is unclear whether brief mechanical events elicit metabolic responses. Here, we applied 1.5-s pressure-driven mechanical stimuli (5-1,000 hPa) to cultured primary rat cortical astrocytes using a patch-micropipette microinjector and monitored cytosolic lactate ([lactate]i) with a Förster resonance energy transfer Laconic nanosensor. Single pressure pulses (5-1,000 hPa) evoked a pressure-dependent increase in [lactate]i that persisted for minutes after stimulation, reaching a steady-state increase of 0.3-4.1% relative to baseline over 200-300 s. Sequential pulses delivered to the same cell produced transient spikes followed by stepwise increases in the post-stimulus plateau, yielding an estimated activation threshold of ~4-5 hPa. Transient receptor-potential vanilloid-4 (TRPV4) immunoreactivity was detected in cultured astrocytes, and pharmacologic inhibition of TRPV4 with HC-067047 attenuated mechanically evoked lactate accumulation during mechanical stimulation by solution bolus addition. These findings demonstrate that astrocytes convert brief mechanical stimuli into prolonged cytosolic lactate increases, supporting a contribution of TRPV4-associated mechanosensitive signaling to astrocytic mechano-metabolic integration.

• Language: English
• Keywords: FRET, TRPV4, astrocytes, lactate, mechano-metabolic coupling, metabolism
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine; BF - Biotechnical Faculty
• Publication status: Published
• Publication version: Version of Record
• Year: 2026
• Number of pages: 14 str.
• Numbering: Vol. 20, art. 1830831
• PID: 20.500.12556/RUL-184377
• UDC: 612.822:577.124:576.32
• ISSN on article: 1662-5102
• DOI: 10.3389/fncel.2026.1830831
• COBISS.SI-ID: 283676419
• Publication date in RUL: 06.07.2026

Record is a part of a journal

• Title: Frontiers in cellular neuroscience
• Shortened title: Front. cell. neurosci.
• Publisher: Frontiers
• ISSN: 1662-5102
• COBISS.SI-ID: 30660825

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: astrocit, laktat, mehansko-presnovna sklopitev, presnova