Formaldehyde initiates memory and motor impairments under weightlessness condition

Area of Science:

• Neuroscience
• Space Biology
• Biochemistry

Background:

• Space flight induces physiological and psychological stress in astronauts, including memory and motor impairments.
• The exact mechanisms behind these deficits during weightlessness remain unclear.
• Hindlimb unloading (HU) models simulate weightlessness and show memory/motor dysfunction linked to formaldehyde (FA) buildup.

Purpose of the Study:

• To review the role of endogenous formaldehyde (FA) in neurological impairments observed during weightlessness.
• To elucidate the mechanisms by which FA affects brain function, extracellular space (ECS), and fluid dynamics.
• To explore FA's potential as a catalyst for memory and motor decline in microgravity.

Main Methods:

• Review of existing studies on hindlimb unloading (HU) animal models.
• Analysis of the impact of formaldehyde accumulation on brain structures and functions.
• Investigation of the role of blood-brain barrier (BBB) integrity and protein interactions.

Main Results:

• FA accumulation in the hippocampus and cerebellum disrupts brain ECS and interstitial fluid (ISF) drainage.
• Impaired BBB allows albumin and hemoglobin infiltration, which FA cross-links with amyloid-beta (Aβ), obstructing ECS and causing neuron death.
• FA inhibits NMDA currents by crosslinking NR1/NR2B subunits, impairs memory, modulates microRNAs (e.g., miRNA-29b) affecting aquaporin-4 (AQP4), and may inactivate ATM kinase.

Conclusions:

• Weightlessness-induced FA accumulation is a critical factor in memory and motor function deterioration.
• FA's cross-linking activity disrupts brain ECS, BBB integrity, and neuronal signaling pathways.
• Understanding FA's role offers potential therapeutic targets for mitigating microgravity's neurological effects.