Melatonin from cerebrospinal fluid but not from blood reaches sheep cerebral tissues under physiological conditions

Area of Science:

• Neuroscience
• Endocrinology
• Pharmacology

Background:

• The pineal gland secretes melatonin (MLT), a hormone circulating in blood and cerebrospinal fluid (CSF).
• Understanding MLT distribution within the brain is crucial for its physiological functions.
• Previous studies have not fully elucidated the differential contribution of blood-borne versus CSF-borne MLT to brain tissue concentrations.

Purpose of the Study:

• To investigate the hypothesis that CSF melatonin, not blood melatonin, is the primary source of MLT in cerebral tissues.
• To quantify MLT concentration gradients within the sheep brain, particularly in periventricular areas.
• To determine the pathways of MLT diffusion into brain tissue.

Main Methods:

• Measurement of MLT concentrations in sheep brain tissue at varying distances from the ventricles during day and night.
• Comparison of MLT concentration gradients following CSF infusion versus intravenous administration.
• In vivo scintigraphy and autoradiography using radiolabeled MLT (2-[(123)I]-MLT) and control substances.

Main Results:

• Significant MLT concentration gradients were observed in sheep brain tissue, decreasing with distance from the CSF-filled ventricles (factor of 1-125).
• Highest MLT concentrations were found near the third ventricle wall (407.0 ± 71.5 pg/ml), decreasing further away (84.7 ± 5.2 pg/ml).
• No such gradient was detected when MLT was administered via the bloodstream, and in vivo imaging confirmed rapid MLT diffusion from CSF into brain tissue.

Conclusions:

• Cerebrospinal fluid (CSF) plays a critical role in delivering melatonin (MLT) to brain tissues.
• MLT distribution within the brain is primarily mediated by diffusion from the CSF, not the bloodstream.
• These findings suggest a specialized pathway for MLT transport within the central nervous system, potentially impacting neurological functions.