Jenny Penschow

The sensory circumventricular organs of the mammalian brain.

The brains three sensory circumventricular organs, the subfornical organ, organum vasculosum of the lamina terminalis and the area postrema lack a blood brain barrier and are the only regions in the brain in which neurons are exposed to the chemical environment of the systemic circulation. Therefore they are ideally placed to monitor the changes in osmotic, ionic and hormonal composition of the blood. This book describes their. General structure and relationship to the cerebral ventricles Regional subdivisions Vasculature and barrier properties Neurons, glia and ependymal cells Receptors, neurotransmitters, neuropeptides and enzymes Neuroanatomical connections Functions.

Sites of expression and induction of glandular kallikrein gene expression in mice.

In order to provide a foundation for comparison across species of glandular kallikrein genes, we have studied the 12 functional mouse genes on the basis of expressing cell types, developmental patterns of expression and gene response to hormonal induction. We have shown expression of the renal kallikrein gene in the female anterior pituitary, the thick ascending limb of renal cortical distal tubules, nasal glands of neonatal mice and at varying levels throughout the duct tree of major salivary glands of immature and adult mice, except for intercalated ducts. This gene did not respond to hormonal induction in salivary glands. The other 11 of the 12 genes are expressed in androgen-responsive cells of granular convoluted tubules of the submandibular salivary gland from 22 days postnatal, when sexual dimorphism of expression first becomes apparent. Expression of these genes is induced prematurely in 22-day-old mice by treatment with testosterone or thyroxine. In the adult female mouse, estrogens also induce elevated levels of expression. One of the glandular kallikrein genes is expressed in Leydig cells of the testis as well as the submandibular gland. This study has extended the basis for cross-species comparison of glandular kallikrein genes.

Morphology of the organum vasculosum of the lamina terminalis (OVLT) of the sheep

Examination of the ventricular surface of the organum vasculosum of the lamina terminalis (OVLT) of sheep with the scanning electron microscope revealed an elongated protuberance occupying most of the frontal wall of the third ventricle below the level of the anterior commissure. This protuberance lacked ciliated ependymal cells. Examination of horizontal sections with the transmission electron microscope revealed an apparent lack of regularly apposed ependymal cells, suggesting that ependyma is either greatly modified or absent. The surface was composed of numerous intertwining cell processes with some scattered cells situated on this surface. The body of this structure was composed of many cell processes separated by a network of extracellular channels sometimes extending to the ventricular surface. Towards the base of this protuberance, a plexus of blood vessels was observed. Some of these vessels exhibited fenestrated endothelium. Neuronal processes were also apparent in this region. These unusual anatomical features suggest a specific function for this brain region in sheep.

REDISTRIBUTION OF CARBONIC ANHYDRASE VI EXPRESSION FROM DUCTS TO ACINI DURING DEVELOPMENT OF OVINE PAROTID AND SUBMANDIBULAR GLANDS

Abstract Carbonic anhydrase VI (CA VI) is a secreted enzyme produced predominantly by serous acinar cells of submandibular and parotid glands. We have investigated the developmental pattern of CA VI production by these glands in the sheep, from fetal life to adulthood, using immunohistochemistry. Also, a specific radioimmunoassay for CA VI was used to measure changes in enzyme expression in the parotid gland postnatally. CA VI is detectable by immunohistochemistry in parotid excretory ducts from 106 days gestation (term is 145 days), in striated ducts from 138 days and in acinar cells from 1 day postnatal. The duct cell content of CA VI declined as the acinar cell population increased, a feature also of CA VI immunoreactivity in the submandibular gland. Production of CA VI by submandibular duct cells was detectable initially at 125 days gestation, and acinar production was not seen before 29 days post-natal. Apart from the differing ontogeny of CA VI production in ducts and acini of parotid and submandibular glands, there was a parallel pattern of CA VI expression during the development of these major salivary glands.With the development of the acinar tissues in the postnatal lamb, there was a dramatic increase (about 600-fold) in the level of expression of CA VI in the parotid gland between days 7 and 59 as measured by radioimmunoassay.

Neurochemical Aspectsof Sensory Circumventricular Organs

For the sensory CVOs to be responsive to circulating factors such as various hormones, peptides or ions, not only do they need the blood-brain barrier to be absent so that they are exposed to this environment, but specific receptors which bind these agents are necessary on the cell surface to specifically detect them.

Vasculature, Compartmental Barriers, Neurons and Glia in the Sensory Circumventricular Organs

The arterial supply and microvasculature of the subfornical organ have been studied in several mammalian species (human, rat, cat, rabbit). Arteries supplying the subfornical enter it both in the ventral stalk as a branch of the preoptic artery and dor-sally and caudally from branches of arteries supplying the choroid plexus (Duvernoy and Koritke 1964). In the rat, the subfornical organ receives a major supply from the subfornical artery which branches from the anterior cerebral artery. To reach the subfornical organ, the subfornical artery passes caudally over the splenium of the corpus collosum, returning rostrally under this fibre tract back towards the subfornical organ through the arachnoid tissue (Spoerri 1963). Before entering the dorsal-caudal aspect of the subfornical organ, this artery is joined by branches of the anterior and posterior choroidal arteries. Veins issuing from the choroid plexus also pass through the subfornical organ of the rat (Figure. 14b, d) and probably other species as well (Spoerri 1963; Duvernoy and Koritke 1964). Within the body of the subfornical organ, arterioles both from dorsal and ventral stalks reticulate into an extensive network of thin capillaries which are sometimes looped and reach near to the ventricular surface (Figure. 14b, c). Capillaries drain rostrally and laterally into large medial septal veins which flow dorsally and may reach the great cerebral vein of Galen.

Location, General Structure and Ependymal Cells of Sensory Circumventricular Organs

Located at seemingly strategic points in the brain’s ventricular system (Figure. 1, 2), the sensory CVOs are midline structures situated in the walls of the third and fourth ventricles. The subfornical organ and OVLT occupy the dorsal and ventral extremities of the lamina terminalis, which embryologically is the most anterior aspect of the developing central nervous system (Bayer and Altman 1987). The subfornical organ appears to guard the entrance of the third ventricle, at the point where the cerebrospinal fluid (CSF) from the lateral ventricles enters the third ventricle, and where its CSF begins to bathe the ventricular surface of the diencephalon and brain stem. At the posterior extremity of the brain, the area postrema, situated in walls of the fourth ventricle at the caudal end of the medulla oblongata, appears to guard the entrance to the central canal of the spinal cord.

The Neural Connections of the Sensory Circumventricular Organs

If the subfornical organ, OVLT and area postrema function as sensors, an essential component for this function will be neural pathways linking these sensory sites to integrative and effector motor regions of the brain. Several neuroanatomical studies have mapped direct efferent connections of the sensory CVOs. These studies have utilised tracer molecules that are transported by axons from their sites of injection either in the anterograde or retrograde direction relative to neuronal cell bodies. Electrophysiological studies have also yielded data that are relevant to the neuronal connectivity of the sensory CVOs.

Regional Subdivisions Within Sensory Circumventricular Organs

It is clear from several points of view that the subfornical organ is not a uniform structure. The subfornical organs of several mammalian species were described by Akert et al. (1961) and subdivided into three regions: a dorsal stalk, the body and ventral stalk. Dellmann and Simpson (1976) also recognised three divisions within the subfornical organ, and, more recently, Sposito and Gross (1987) and Shaver et al. (1990) subdivided the subfornical organ of the rat into a number of regions, largely on the basis of capillary morphology and distribution. These were rostral, transitional, central and caudal subregions, with dorsal, ventromedial and lateral zones of the latter three subregions. Other studies of neural connectivity, receptor binding, histo-chemical staining and functional neuroanatomy utilising c-fos expression are indicative of two major functional subdivisions of the rat subfornical organ: the first is a rostrodorsal ’outer shelP which includes the ventral and dorsal stalks of the original classification and dorsal and lateral zones of all regions specified by Sposito and Gross (1987); the second subdivision is a central Ventromedial core’ of the subfornical organ, corresponding to the ventromedial zone of Sposito and Gross (1987). A schematic diagram of the subdivisions of the rat subfornical organ is presented in Figure. 11.

Immediate-Early Gene Expression in Sensory Circumventricular Organs

During the past 15 years, study of expression of genes such as c-fos and c-jun has provided invaluable tools for studying the function of either individual cells or whole populations of neurons in the CNS. This approach has been especially helpful in studying the sensory circumventricular organs, where blood-borne stimuli that do not cross the blood-brain barrier interact with neurons in these regions. After stimulation of a neuron, either through its synaptic input or hormonal receptors or by transduction of stimuli related to its sensory role, second messenger pathways are engaged. These lead to increased intracellular calcium levels that subsequently result in the increased expression of a number of genes that include c-fos. Synthesis of its encoded protein product, Fos, follows. This protein forms heterodimers with other proteins, and these bind to API sites in DNA to act as a regulator of gene transcription (Morgan and Curran 1989b). Activated neurons can thus be identified either by immunohistochemical techniques to detect Fos, the protein encoded by c-fos, or by in situ hybridisation identification of its mRNA (Morgan et al. 1987; Hunt et al. 1987; Dragunow and Faull 1989; Morgan and Curran 1989a, b; Ceccatelli et al. 1989; Hoffman et al. 1990).