Cellular lining of the sheep pineal recess studied by light‐, transmission‐, and scanning electron microscopy: Morphologic indications for a direct secretion of melatonin from the pineal gland to the cerebrospinal fluid

Abstract

In the sheep, the pineal hormone melatonin displays nocturnal levels 20 times as high in the cerebrospinal fluid of the third ventricle as in the jugular blood. Moreover, in the pineal recess, the evagination of the third ventricle into the pineal stalk, the levels of melatonin in the cerebrospinal fluid are even higher than in the ventral part of the third ventricle. This finding suggests melatonin to be secreted directly from the pineal gland to the ventricular lumen of the pineal recess of this species. We have, therefore, studied the interface between the sheep pineal gland and the cerebrospinal fluid by light-, scanning-, and electron microscopy of the pineal recess, as well as the permeability of the interface by tracer injections into the third ventricle. First, we show that the classic ependymal lining of the third ventricle disappears in the superior part of the recess. In this area, bulging pinealocytes, displaying immunoreactivity for serotonin, directly appose the cerebrospinal fluid. This pineal-cerebrospinal fluid interface of the sheep is large compared with other species, especially rodent species. Intraventricular injections of horseradish peroxidase and fluorescein isothiocyanate showed that both these tracers could permeate from the pineal recess into the sheep pineal parenchyma. This permeation was due to the presence of gap and intermediate junctions connecting the pinealocytes apposing the ventricular lumen. Thus, our results show that endocrine cells in this specialized area of the ventricular system are in direct contact with the cerebrospinal fluid. This finding supports the physiological concept of a direct secretion of melatonin into the cerebrospinal fluid of the sheep pineal recess.

Melatonin Metabolism in the Central Nervous System

“…This should be particularly important after administration of exogenous melatonin. To what extent the circulating hormone contributes, under physiological conditions, to its brain concentrations is not fully understood, specially as the pineal itself releases the indoleamine at much higher concentrations directly via the pineal recess to the third ventricle [146][147][148]. The appearance of melatonin in the third ventricle has been very recently demonstrated in humans, but the amounts reported are relatively moderate (about 8.75 pg/mL) [74].…”

Endoscopic Selective Sampling of Human Ventricular CSF: A New Perspective

“…Consistent with some observations, the pineal recess CSF could constitute an entry point to the third ventricle for melatonin, through the glandular extracellular fluid or directly from the pinealocytes which overlook the ventricular cavity [23]. In this way, due to the small volume of the whole CSF, a smaller quantity than that released in the bloodstream of this hormone would reach higher concentrations than those in the plasma.…”

The Use of Melatonin as a Chronobiotic-Cytoprotective Agent in Sleep Disorders

“…However, an important question, not yet adequately solved, concerns as to what "physiological" means in terms of intracerebral melatonin levels The levels of a lipophilic substance like melatonin reaching neurons under physiological conditions may differ considerably from circulating hormone concentration. In sheep, third ventricle cerebrospinal fluid (CSF) melatonin concentration was 20-fold higher than concomitant plasma values (Skinner and Malpaux, 1999;Tricoire et al, 2002Tricoire et al, , 2003. In 12-month old mice 6-sulphatoxymelatonin concentration was approximately 1000-fold greater than that of melatonin in the cerebral cortex (Lahiri et al, 2004b).…”