Microscopically the pineal
appears as clusters of parenchymal cells enclosed by bands of connective tissue
of variable thickness that consist of fibrous astrocytes and other cell types.
The pineal is surrounded by a capsule and is composed of lobules with separating
connective tissue septae. Astrocytes are shown to be abundant by glial
fibrillary acidic protein (GFAP) staining and form a barrier between vessels and
There are many different cell
types in the gland. In addition to supporting, neuronal, and endothelial cells,
the stroma is made up of pinealocytes, which themselves may be subdivided by
histologic and electron microscopic, and increasingly by biochemical and
Pinealocytes make up 90 percent
of the parenchyma of the gland. In sub mammalian species, they are derived from
photoreceptor cells. In vertebrates there are thought to be two types of pineal
cells, light and dark, so named on the basis of their responsiveness or
unresponsiveness to light input at the retina, The existence of these two types
in humans remains controversial.
Parenchymal pineal cells are
thought to belong to the system of amine precursor uptake and decarboxylation
(APUD) cells. They stain positively for neuron-specific enolase.
Pinealocytes are characterized
by their prominent nuclei and nucleoli. Each pinealocyte has several cytoplasmic
processes, which terminate in club-shaped endings on perivascular spaces and
which may provide a means for communication between pinealocytes.
Because it produces substances
chemically related to neurotransmitters, contains synaptic vesicles, secretes
its products in response to stimulation of receptors on its cell membrane and
originates in the ectoderm, the pinealocyte can be considered a "paraneuronal"
cell. Kappers considers the pineal "a true endocrine organ" because
pinealocytes, although derived from neuroectoderm, are not neurons.
In lower animals, pinealocytes
morphologically resemble retinal photoreceptor cells. Some of the pinealocytes
in these species have processes that resemble axons and many of them
immuno-stain positively for gamma-aminobutyric acid (GABA).
Glial cells, primarily fibrous
astrocytes, appear to serve both supportive and metabolic roles in the pineal,
as they do in all central nervous system tissue. Staining with S-100 suggests
that microglial cells are also present.
The endothelial cells that make
up the vascular supply to the pineal do not have the tight junctions
characteristic of the bloodbrain barrier: the pineal is thus rightly considered
to be a circumventricular organ. Although parasympathetic, commissural. and
peptidergic fibers have been demonstrated in the pineal. the only fibers with
known physiologic significance in the gland are general visceral afferent
sympathetics originating in the superior cervical ganglion and reaching the
pineal via the nervi conarii. These postganglionic sympathetic fibers receive descending input from hypothalamic nuclei, particularly the suprachiasmatic
nucleus (SCN), which receives direct input from retinal ganglion cells.
Unmyelinated fibers travel through connective tissue in discrete bundles. In
some animals all the sympathetic input reaches the pineal as unmyelinated fibers
traveling with venules and arterioles, which vascularize the gland. There is
also questionable parasympathetic innervation, possibly arriving via the
habenula and posterior commissure. Neurotransmitters reach pineal cells not
across a synaptic cleft but by diffusion after release from varicosities some
distance away. Other cell and tissue types found in the pineal include fibrous
connective tissue, skeletal muscle and lymphocytes.
Acervuli, corpora arenacea, or
pineal calcifications, the familiar and important pineal landmarks seen on skull
roentgenography and computed tomography (CT) of the head are still incompletely
understood. Calcium accumulates along plasmalemma and intracellularly in
pinealocytes. This may be the basis of calcium deposition, which occurs in an
organic matrix produced by pinealocytes. The calcareous concretions grow along
growth zones and are composed of calcium, magnesium and ammonium ions as well as
calcium carbonate. The growth process is thought to be age- and sex-independent
and is probably related to the gland's secretory activity.
Although the etiology of these
concretions is not known, two theories have been proposed. In the first a
carrier protein is thought to be released into intracellular vacuoles. In the
second there is decreased drainage of tissue fluid from the gland. Acervuli are
seen in 3 percent of pineals by age 1 year, in 7.1 percent by age 10, and in 33
percent by age 18.
The functional significance of
pineal calcifications is unknown. Recent CT studies of pineal calcifications
have attempted to correlate their presence with diseases such as schizophrenia.
Another incompletely understood
phenomenon is the formation of benign pineal cysts. These mass lesions, which
can reach proportions sufficient to result in clinical symptoms and signs, are
thought to result either from degeneration of foci of gliosis within the gland
or from sequestration of CSF during pineal development. Why this happens remains
unknown. In a recent radiologic review, Golzarian et al. reported a 2,4 percent
incidence in 500 consecutive magnetic resonance imaging studies. Pineal cysts
can be found in 25 to -40 percent of subjects studied at autopsy.