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Melatonin enters the cerebrospinal fluid through the pineal recess
Hélène Tricoire1, Alain Locatelli, Philippe Chemineau
1Unité Mixte de Recherche Institut National de la Recherche Agronomique-Centre National de la Recherche Scientifique (6073), Université de Tours "Physiologie de la Reproduction et des Comportements," 37380 Nouzilly, France.
Abstract:
The pineal recess (PR), a third ventricle (IIIV) evagination penetrating into the pineal gland, could constitute a site of melatonin passage to the cerebrospinal fluid (CSF) and explain the high concentrations of melatonin in this fluid. To test this hypothesis, we characterized melatonin distribution in the IIIV of sheep by CSF collection in the ventral part of IIIV (vIIIV) and in PR. At 30 microl/min collection rate, melatonin concentrations were much higher in PR than in vIIIV (19,934 +/- 6,388 vs. 178 +/- 70 pg/ml, mean +/- SEM, respectively, P < 0.005), and they increased in vIIIV when CSF collection stopped in the PR (P < 0.05). At 6 microl/min, levels increased to 1,682 +/- 585 pg/ml in vIIIV and were not influenced by CSF collection in the PR. This concentration difference between sites and the influence of PR collection on vIIIV levels suggest that melatonin reaches the PR and then diffuses to the IIIV. To confirm the role of PR, we demonstrated that its surgical sealing off decreased IIIV melatonin levels (1,020 +/- 305 pg/ml, compared with 5,984 +/- 1,706 and 6,917 +/- 1,601 pg/ml in shams or animals with a failed sealing off, respectively, P < 0.01) without changes in blood levels. Therefore, this study identified the localization of the main site of penetration of melatonin into the CSF, the pineal recess.
Insights
The pineal recess is the main site where melatonin enters cerebrospinal fluid (CSF). Surgical sealing of the pineal recess significantly reduced CSF melatonin levels, confirming its role in melatonin transport.
Area of Science:
- Neuroendocrinology
- Cerebrospinal Fluid Dynamics
- Pineal Gland Physiology
Background:
- The pineal recess (PR), an extension of the third ventricle into the pineal gland, is hypothesized to be a key site for melatonin transfer into the cerebrospinal fluid (CSF).
- High melatonin concentrations observed in CSF suggest a specific entry point, potentially the PR.
Purpose of the Study:
- To investigate the role of the pineal recess (PR) as the primary site of melatonin entry into the cerebrospinal fluid (CSF).
- To quantify melatonin distribution within the third ventricle (IIIV) and PR in sheep.
Main Methods:
- CSF was collected from the ventral third ventricle (vIIIV) and PR in sheep at different collection rates (30 and 6 microl/min).
- Melatonin concentrations were measured in collected CSF samples.
- The effect of PR CSF collection on vIIIV melatonin levels was assessed.
- The impact of surgically sealing the PR on IIIV melatonin levels was evaluated and compared to sham surgeries.
Main Results:
- Melatonin concentrations were significantly higher in the PR compared to the vIIIV (19,934 vs. 178 pg/ml at 30 microl/min).
- Cessation of CSF collection in the PR led to increased melatonin levels in the vIIIV.
- Surgical sealing of the PR markedly reduced IIIV melatonin levels (1,020 pg/ml) compared to controls (5,984-6,917 pg/ml), without affecting blood melatonin levels.
Conclusions:
- The pineal recess serves as the principal site for melatonin's entry into the cerebrospinal fluid.
- Melatonin diffuses from the PR into the third ventricle, explaining elevated CSF melatonin concentrations.
- These findings elucidate a critical pathway for melatonin transport within the central nervous system.