Cerebrospinal fluid mesencephalic astrocyte-derived neurotrophic factor: A moderating effect on sleep time and cognitive function.

ABSTRACT

BACKGROUND: Sleeping late has been associated with cognitive impairment, and insufficient sleep can affect the secretion of feeding-related cytokines. Feeding-related cytokines may contribute to cognitive deficits resulting from delayed bedtime. Glial cell line-derived neurotrophic factor (GDNF) and mesencephalic astrocyte-derived neurotrophic factor (MANF), which are feeding-related neurotrophic factors, have been associated with improved cognitive function and neuroprotective abilities. Enhanced expression of GDNF and MANF is linked to increased energy expenditure and hyperphagia, respectively. AIMS: This study aimed to investigate the association between cerebrospinal fluid (CSF) GDNF, MANF, cognition, and sleep time and to explore the moderating effects of GDNF and MANF on cognitive impairment in individuals who sleep late. METHOD: This cross-sectional study included participants (mean age 31.76 ± 10.22 years) who were categorized as ≤23 o'clock sleepers (n = 66) and >23 o'clock sleepers (n = 125) based on sleep time. Cognition was assessed using Montreal Cognitive Assessment (MoCA), and GDNF and MANF levels in CSF were measured. RESULTS: MANF may play a moderating role in the relationship between sleep time and cognition (R2 = 0.06, ß = 0.59, p = 0.031). Age showed a negative correlation with MoCA scores (R2 = 0.08, ß = -0.18), while education exhibited a positive correlation (ß = 0.17, both p < 0.05). Only ≤23 o'clock sleepers exhibited a negative correlation between MANF levels and BMI (r = -0.35, p = 0.005). CONCLUSIONS: This study provides hitherto undocumented evidence of the potential protective effect of CSF MANF on cognitive impairment of late sleepers, which suggests that maintaining a regular sleep schedule may contribute to cognition and overall health, with MANF playing a role in this process.