The morphological correlates of primate cerebrospinal fluid absorption

Arachnoid villi from cynomolgus monkeys subjected to various states of cerebrospinal fluid (CSF) absorption have been examined with scanning (SEM) and transmission (TEM) electron microscopy. Pressures within the superior sagittal sinus and the subarachnoid space were rigidly controlled, both prior to and during perfusion fixation and, as such, we created and studied conditions of normal, absent and increased cerebrospinal fluid absorption. Under normal conditions, the most prominent feature of the CSF/blood interface was the presence of endothelial intracytoplasmic vacuoles. The presence of these vacuoles was suggested with SEM and readily confirmed with TEM. Occassionally, these vacuoles coalesced with both the CSF and sagittal sinus fronts, thereby creating transcellular channels as identified by TEM or surface pores as seen with SEM. Villi perfused during conditions of no CSF flow exhibited none of the previously described vacuoles, channels, or pores, whereas increased CSF flows were associated with increased numbers of these structures. The significance of these findings was discussed in relation to CSF absorption and to previously reported ultrastructural studies.     

Corticopontine projections from the cingulate cortex in the rhesus monkey

The corticopontine projections of the cingulate cortices were investigated in the rhesus monkey with the use of autoradiography. A well-organized topography of projections was observed with anterior cingulate cortex projecting to the medial part of the pontine gray matter and posterior cingulate cortex projecting to the lateral part. Together these projections form a circle of termination around the periphery of the pontine gray matter.     

Distribution of phenylethanolamine N-methyltransferase cell bodies, axons, and terminals in monkey brainstem: an immunohistochemical mapping study

Adrenaline (epinephrine) is an important candidate transmitter in descending spinal control systems. To date intrinsic spinal adrenergic neurons have not been reported; thus adrenergic input is presumably derived from brainstem sites. In this regard, the localization of adrenergic neurons in the brainstem is an important consideration. Maps of adrenergic cell bodies and to a lesser extent axons and terminal fields have been made in various species, but not in monkeys. Thus, the present study concerns the organization of adrenergic systems in the brainstem of a monkey (Macaca fascicularis) immunohistochemically mapped by means of an antibody to the enzyme phenylethanolamine N-methyltransferase (PNMT). PNMT-immunostained cell bodies are distributed throughout the medulla in two principal locations. One concentration of labeled cells is in the dorsomedial medulla and includes the nucleus of the solitary tract (NTS), the dorsal motor nucleus of the vagus (X), and an area ventral to X in a region of the reticular formation (RF) known as the central nucleus dorsalis (CnD) of the medulla. A few scattered cells are observed in the periventricular gray just ventral to the IVth ventricle and on midline in the raphe. The second major concentration of PNMT-immunostained cells is located in the ventrolateral RF, lateral and dorsolateral to the inferior olive (IO), including some cells in the rostral part of the lateral reticular nucleus (LRN). Terminal fields are located in the NTS, X, area postrema (AP), and the floor of the IVth ventricle in the medulla and pons. A light terminal field is also observed in the raphe, particularly raphe pallidus (RP). A heavy terminal field is present in locus coeruleus (LC). Fibers labeled for PNMT form two major fiber tracts. One is in the dorsomedial RF extending as a well-organized bundle through the medulla, pons, and midbrain. A second tract is located on the ventrolateral edge of the medulla and caudal pons. Fibers in this tract appear to descend to the spinal cord. A comparison with maps of other catecholamine neurons in primates is discussed, confirming that the distribution of the adrenergic system in monkeys is similar to that described in the human.     

High versus low pressure receptors in modulating the volumetric control of antidiuretic hormone secretion in the monkey

Summary Experiments were carried out in sixMacaca fascicularis monkeys to determine the relationships between arterial pressure (AP) and plasma arginine vasopressin (AVP) and left ventricular enddiastolic pressure (LVEDP) and plasma AVP in response to a two-step hemorrhage. In response to each hemorrhage, there occurred a significant decline in AP, a significant elevation of plasma AVP and variable but nonsignificant changes in LVEDP. These results are consistent with the hypothesis that in the primate high pressure receptors are more important than low pressure receptors in the volumetric control of AVP secretion.Supported by National Research Service Award L F32 HL05832 from the National Heart Lung and Blood Institute.     

Neuropeptides in cerebral cortex of macaque monkey (Macaca fuscata fuscata): Regional distribution and ontogeny

The concentrations of vasoactive intestinal polypeptide, somatostatin and substance P were determined in various cerebral subdivisions of adult and foetal Japanese monkeys (Macaca fuscata fuscata) by specific radioimmunoassays. In adult tissues, the highest level of vasoactive intestinal polypeptide was found in the somatosensory cortex and the lowest level in the occipital cortex. A high level of somatostatin was found in the association cortex (prefrontal, parietal and temporal cortex); the lowest level was noted in the occipital cortex. Substance P was found to be high in prefrontal and temporal cortex. The highest levels of substance P and somatostatin were obtained in the amygdala. Between embryonic 4 and 5.5 months, concentrations of peptides increased dramatically, and in the adult, all neuropeptides in cortical subdivisions significantly decreased. By the gel filtration method, only one immunoreactivity which coeluted with substance P and vasoactive intestinal polypeptide was demonstrated in extracts of 4-, 5.5-month-old and adult monkey cerebral cortex. In contrast, somatostatin immunoreactivity eluted as 3 peaks. Almost 80% of the immunoreactivity co-eluted with synthetic somatostatin, regardless of the age of the tissue. The molecular weights of two larger molecules were determined to be 13 and 3 kdaltons.     

Differential effects of prostaglandins on mesenteric and cerebral arteries isolated from premature newborn baboons

Responses to prostaglandins (PGs) E₁, E₂, F₂ and I₂ at a wide range of concentrations were compared in the cerebral and mesenteric arteries isolated from premature newborn baboons. PGE₁ at low concentrations relaxed the cerebral artery but not the mesenteric artery. PGI₂ produced a relaxation of similar magnitude in both arteries. PGF₂ in high concentrations produced a much greater contraction in the mesenteric artery than in the cerebral artery. Thus, during the perinatal stage, the baboon cerebral artery has distinctive PG-reactivity compared to the extracerebral artery. Clinical use of PGE₁ or indomethacin may result in circulatory derangement or redistribution of blood flow in the cerebral and mesenteric circulations, and may produce side effects of these drugs.Abbreviation PG prostaglandin     

Effects of tryptophan depletion on the binding of [11C]-DASB to the serotonin transporter in baboons: response to acute serotonin deficiency.

BACKGROUND: The objective of this study was to evaluate the sensitivity of [(11)C]-N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine (DASB) binding to the brain serotonin transporter (SERT) to changes in endogenous serotonin (5-hydroxytryptamine [5-HT]) levels. A ligand sensitive to endogenous competition (EC) would enable the measurement of fluctuations of intrasynaptic 5-HT. A ligand insensitive to EC can provide a measure of SERT unaffected by levels of 5-HT. Alternatively, serotonin depletion could accelerate internalization of SERT and reduce binding. METHODS: Eighteen (14 baseline and 9 tryptophan-depleted) positron emission tomography (PET) scans were carried out in two baboons (Papio anubis). A metabolite-corrected arterial input function was used to estimate the binding potential (BP = B(max)/K(D)). RESULTS: Depletion of plasma tryptophan by a mean of 65% from the baseline (p = .03) reduces [(11)C]-DASB BP in the six brain regions of interest (ROI). Lower DASB binding correlated with lower plasma tryptophan levels in the ROIs with higher SERT density. CONCLUSIONS: [(11)C]-DASB binding to SERT in vivo rapidly declines in response to acute reduction in serotonin availability, contrary to what is predicted by a simple competition model. This rapid reduction in SERT availability may be due to accelerated transporter internalization.     

Topographical and cytological localization of iron in rat and monkey brains

The topographical localization of endogenous iron in rat and monkey brains coincides with the striato-pallido-nigral and the cerebellar corticonuclear pathways. EM observation reveals that iron is located in the soma and processes of glial cells and, above all, in the inner and outer loop of the myelin sheets. This raises the question of whether iron intervenes in some GABAergic systems.     

Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation,bone mineral density,and bone strength

The development of bone‐rebuilding anabolic agents for treating bone‐related conditions has been a long‐standing goal. Genetic studies in humans and mice have shown that the secreted protein sclerostin is a key negative regulator of bone formation. More recently, administration of sclerostin‐neutralizing monoclonal antibodies in rodent studies has shown that pharmacologic inhibition of sclerostin results in increased bone formation, bone mass, and bone strength. To explore the effects of sclerostin inhibition in primates, we administered a humanized sclerostin‐neutralizing monoclonal antibody (Scl‐AbIV) to gonad‐intact female cynomolgus monkeys. Two once‐monthly subcutaneous injections of Scl‐AbIV were administered at three dose levels (3, 10, and 30 mg/kg), with study termination at 2 months. Scl‐AbIV treatment had clear anabolic effects, with marked dose‐dependent increases in bone formation on trabecular, periosteal, endocortical, and intracortical surfaces. Bone densitometry showed that the increases in bone formation with Scl‐AbIV treatment resulted in significant increases in bone mineral content (BMC) and/or bone mineral density (BMD) at several skeletal sites (ie, femoral neck, radial metaphysis, and tibial metaphysis). These increases, expressed as percent changes from baseline were 11 to 29 percentage points higher than those found in the vehicle‐treated group. Additionally, significant increases in trabecular thickness and bone strength were found at the lumbar vertebrae in the highest‐dose group. Taken together, the marked bone‐building effects achieved in this short‐term monkey study suggest that sclerostin inhibition represents a promising new therapeutic approach for medical conditions where increases in bone formation might be desirable, such as in fracture healing and osteoporosis. © 2010 American Society for Bone and Mineral Research