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

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

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.

• Jezik: Angleški jezik
• Ključne besede: FRET, TRPV4, astrocytes, lactate, mechano-metabolic coupling, metabolism
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: MF - Medicinska fakulteta ; BF - Biotehniška fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2026
• Št. strani: 14 str.
• Številčenje: Vol. 20, art. 1830831
• PID: 20.500.12556/RUL-184377
• UDK: 612.822:577.124:576.32
• ISSN pri članku: 1662-5102
• DOI: 10.3389/fncel.2026.1830831
• COBISS.SI-ID: 283676419
• Datum objave v RUL: 06.07.2026

Gradivo je del revije

• Naslov: Frontiers in cellular neuroscience
• Skrajšan naslov: Front. cell. neurosci.
• Založnik: Frontiers
• ISSN: 1662-5102
• COBISS.SI-ID: 30660825

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: astrocit, laktat, mehansko-presnovna sklopitev, presnova