The cutaneous branch of the mylohyoid nerve in the crab-eating monkey (Macaca fascicularis)

Cutaneous branches of the mylohyoid nerve were observed in both sides of 25 (83.3%) and in one side of 5 (16.7%) out of 30 crab-eating monkeys (Macaca fascicularis). The branch supply the skin and sinus hairs at the mental part. These sinus hairs seem to be the intermandibular sinus hairs according to the manner of nerve supply.     

Craniorachischisis and omphalocele in a stillborn cynomolgus monkey (Macaca fascicularis)

Nonhuman primates have been a common animal model to evaluate experimentally induced malformations. Reports on spontaneous malformations are important in determining the background incidence of congenital anomalies in specific species and in evaluating experimental results. Here we report on a stillborn cynomolgus monkey (Macaca fascicularis) with multiple congenital anomalies from the colony maintained at the Southwest National Primate Research Center at the Texas Biomedical Research Institute, San Antonio, Texas. Physical findings included low birth weight, craniorachischisis, facial abnormalities, omphalocele, malrotation of the gut with areas of atresia and intussusception, a Meckel diverticulum, arthrogryposis, patent ductus arteriosus, and patent foramen ovale. The macaque had normal male external genitalia, but undescended testes. Gestational age was unknown but was estimated from measurements of the limbs and other developmental criteria. Although cytogenetic analysis was not possible due to the tissues being in an advanced state of decomposition, array Comparative Genomic Hybridization analysis using human bacterial artificial chromosome clones was successful in effectively eliminating aneuploidy or any copy number changes greater than approximately 3-5 Mb as a cause of the malformations. Further evaluation of the animal included extensive imaging of the skeletal and neural tissue defects. The animal's congenital anomalies are discussed in relation to the current hypotheses attempting to explain the frequent association of neural tube defects with other abnormalities.     

Neuropeptide Y (NPY)-like immunoreactive nerve fibers in the human and monkey (Macaca fascicularis) kidney

Nerve fibers immunoreactive for neuropeptide Y (NPY) are demonstrated for the first time by the indirect immunofluorescence technique in the human and monkey kidney. NPY-like immunoactivity (NPY-LI) is shown in a bundle of nerve fibers in the surrounding connective tissue of arteries and to a lesser extent, veins, mainly at the juxtamedullary region. Varicose nerve terminals are shown associated with blood vessels and passing between tubules in the mid and lower cortex. NPY-LI nerve fibers are also seen surrounding afferent and occasionally efferent arterioles at the vascular pole of the glomeruli. The distribution of NPY-LI nerve fibers in the monkey and human kidneys is similar to that of other species, only the quantity of the nerve fibers varies.     

Distribution of sympathetic nerve endings within the rabbit carotid body: a histochemical and ultrastructural study

Summary The distribution of sympathetic (noradrenergic) nerves within the rabbit carotid body was investigated by fluorescence microscopy and electron microscopy. With the Falck-Hillarp method, fluorescent nerve fibres were found associated with blood vessels and type I/type II cell groups. After the injection of 6-hydroxydopamine, degenerating nerve profiles were found near blood vessels, near type I/type II cell groups and in contact with type II cells. Following the administration of [³H]noradrenaline, labelled nerve profiles were observed in close association with blood vessels and around cell groups; a few labelled nerve profiles were observed in contact with type II cells. With a modified chromaffin method, chromaffin nerve profiles were found around blood vessels, around type I/type II cell groups and their sensory nerve supply and in contact with type II cells. It was shown that for about one-third of the chromaffin nerve profiles, the nearest structure (in the plane of section) was a type I/type II cell group. Furthermore, the mean distance between chromaffin nerve profiles and blood vessels and between chromaffin nerve profiles and type I/type II cell groups was about the same (2.2 m and 2.7 m respectively). These results suggest that the carotid body sympathetic innervation might have, in addition to its vasomotor function, a direct action on the chemosensory structures. This hypothesis is discussed in the light of currently available physiological data and a comparison is made with the role of the sympathetic innervation in other sensory systems.     

Foregut cyst of the oesophageal wall in a cynomolgus monkey (Macaca fascicularis)

Congenital oesophageal cysts of foregut origin are rare in animals and human beings. This report describes a case in a 4-year-old cynomolgus monkey with no clinical symptoms. The cyst, which was located within the oesophageal submucosal tissue near the mid-point of the oesophagus, was lined with pseudostratified ciliated epithelium and had a thin layer of submucosal tissue. The cyst was surrounded by a smooth muscle layer which was partly intermingled with the circular muscle layer of the oesophagus. The muscularis mucosae of the oesophagus was not shared with the cyst wall. Simple tubular glands were present, opening into the cyst lumen. No communication between the cyst lumen and the oesophagus was observed. Cartilaginous tissue, which is a diagnostic feature of bronchogenic cysts, was not identified in the cyst wall. On the basis of the histopathological features, a foregut cyst of the oesophagus was diagnosed.     

Sebaceous gland metaplasia in the oesophagus of a cynomolgus monkey (Macaca fascicularis)

Microscopical evaluation of tissues from a mature female cynomolgus monkey assigned to a 13-week oral toxicity study revealed nests of sebaceous cells within the mucosa of the distal oesophagus. The sebaceous cell nests showed normal differentiation from basally-oriented seboblasts to centrally-orientated mature sebocytes. No excretory ducts were found, but solitary or small groups of vacuolated sebocytes were present in the overlying normal, non-keratinized squamous epithelium. The finding of sebaceous cells, of presumed ectodermal origin, in the oesophageal mucosa, which is of endodermal origin, is of scientific interest. Different theories may explain the existence of this peculiarity, but sebaceous gland metaplasia is the most plausible. The mucosal change was thought to be unrelated to treatment and is the first case of sebaceous gland metaplasia reported in the oesophagus of a non-human primate.     

Norepinephrine-containing glomus cells in the rabbit carotid body. I. Autoradiographic and morphometric study after tritiated norepinephrine uptake

Summary Rabbit carotid bodies were investigated by autoradiography at both the light and electron microscope levels following tritiated norepinephrine administration eitherin vivo orin vitro. Two kinds of labelled structures were found: nerve fibres (absent in sympathectomized carotid bodies) and some type I glomus cells. Desipramine (a specific norepinephrine uptake inhibitor) prevented labelling. Most of the labelled cells differed from unlabelled ones by the presence of (i) large dense-cored vesicles characterized by a large halo between the membrane and an eccentric dense core; (ii) a nucleus showing a more electron dense chromatin and a more irregular shape; and (iii) relatively abundant glycogen particles. A few weakly-labelled cells were characterized by a pyknotic nucleus and very swollen dense-cored vesicles, and were presumed to be degenerating.Dense core diameters of dense-cored vesicles were distributed according to a unimodal distribution in labelled cells as in unlabelled ones but with an extension towards both large and very small diameters in labelled cells. The mean diameter was higher in labelled cells than in unlabelled ones (127 nm versus 113 nm,P < 0.01). The labelling intensity (as estimated by the number of silver grains per unit of cytoplasmic area) was maximum in cells having dense-cored vesicles whose mean diameter was between 130 and 170 nm, but decreased for cells with mean diameter of dense cores smaller than 130 nm, or larger than 170 nm.Thus, in the rabbit carotid body, some glomus cells differ from others by their ability to take up tritiated norepinephrine and by the presence of larger dense-cored vesicles. However, this distinction is not clearcut and there are many intermediates. The observations suggest a phenomenon of evolution deriving from a unique cell type and typified by both metabolic norepinephrine uptake ability, glycogen accumulation) and morphologic changes (increase in diameter of dense-cored vesicles). It seems, therefore, more appropriate to consider these results in terms of different functional states rather than different types of glomus cells.     

Ultrastructure of the glomus cells in the carotid body of chronically hypoxic rats: With special reference to the similarity of amphibian glomus cells

The ultrastructural characteristics of the glomus cells in the rat carotid body exposed to extremely long-term hypoxia (10–12 weeks) were investigated. The glomus cells could be classified into four distinct types according to the shape of dense-cored vesicles in the glomus cell cytoplasm: (1) small vesicle cells (SVCs, 50 nm in mean diameter), (2) large vesicle cells (LVCs, 80 nm in mean diameter), (3) dilated eccentric vesicle cells (EVCs, 400–800 nm in diameter), and (4) mixed vesicle cells (MVCs, large and eccentric vesicles). Many clusters of glomus cells were found to contain all four categories of cell types. The appearance of EVCs was a unique and common characteristic of glomus cells in this long-term hypoxia model. We also noted other ultrastructural features with chronic hypoxia which are characteristic of the amphibian carotid labyrinth glomus cells: (1) incomplete covering of glomus cells with the supporting cell missing over a wide area, (2) long thin cytoplasmic projections in the intervascular stroma, and (3) intimate apposition of the glomus cells and pericytes (g-p connection), endothelial cells (g-e connection), plasma cells, and fibrocytes. Because arterial PO₂ is generally low in amphibia, these may be general features of hypoxic adaptation and facilitate both uptake of oxygen from blood and release of catecholamine into the blood. The g-p and g-e connections may take part in the regulation of the microcirculation in the enlarged carotid body. © 1993 Wiley-Liss Inc.     

Two types of periglomerular cells in the olfactory bulb of the macaque monkey (Macaca fascicularis)

The olfactory bulb (OB) of mammals is the brain region that receives the sensory information coming from the olfactory epithelium. The entrance of the olfactory information occurs in spherical structures of neuropil named olfactory glomeruli and is modulated by a population of interneurons known as periglomerular cells (PG). It has been demonstrated that there are two types of PG in the OB of some macrosmatic mammals, including rats and mice. Type 1 PG (PG-1) receive synapses from the olfactory nerve, whereas type 2 PG (PG-2) do not receive synapses from the olfactory axons. To date, the presence of the two types of PG has not been investigated in microsmatic mammals. In this context, we analyze the presence of PG-1 and PG-2 in the OB of the long-tailed macaque (Macaca fascicularis). For that, we used the enzyme tyrosine hydroxylase, the neuronal isoform of the enzyme nitric oxide synthase and the calcium-binding proteins calbindin D-28k and calretinin as neurochemical markers. Our results demonstrate that the OB of the macaque contains PG-1 and PG-2. A subpopulation of PG-1 expresses tyrosine hydroxylase and another expresses the neuronal isoform of nitric oxide synthase. In addition, a subpopulation of PG-2 expresses calbindin D-28k and another expresses calretinin. Double immunofluorescence demonstrates that there is no colocalization of two markers in the same PG. These results mimic those found in macrosmatic animals. The presence of two types of PG in the glomerular circuits seems to be a key principle for the organization of the OB of mammals.     

Characterization of Meibomian gland innervation in the cynomolgus monkey (Macaca fascicularis)

To characterize the innervation of the cynomolgus monkey (Macaca fascicularis) Meibomian (tarsal) glands, upper lids of six cynomolgus monkeys were investigated with electronmicroscopical and double-labeling immunocytochemical methods. Antibodies against calcitonin gene-related peptide (CGRP), dopamine-β-hydroxylase (DBH), neuropeptide Y (NPY), nitric oxide synthase (NOS), protein gene product 9.5 (PGP 9.5), substance P (SP), tyrosine hydroxylase (TH), and vasoactive intestinal peptide (VIP) were used. In addition, sections were processed for NADPH-diaphorase (NADPH-d) histochemistry. Staining for PGP 9.5 and electron microscopy showed that Meibomian gland acini were surrounded by a network of unmyelinated nerves and terminal varicose axons. The terminals contained small agranular (30–60 nm) and large granular vesicles (65–110 nm), and were observed in close contact with the basal lamina of the acini, but never internally to the basal lamina. Meibomian axons showed like-immunore-activity (LI) for the neuropeptides SP, CGRP, NPY, and VIP. In addition, the axons stained for TH, DBH, NOS, and NADPH-d. VIP-LI, NOS- and NADPH-d-positive axons appeared to be more numerous, TH- and DBH-positive axons more rare than others. Most SP-LI axons were double-labelled for CGRP-LI, some for VIP-LI or NPY-LI. In addition, some VIP-LI axons were double-labeled for NPY-LI. NPY/VIP-LI and NPY/SP-LI axons were only observed close to the Meibomian acini. Conversely, NPY-LI colocalized with TH-IR or DBH-IR predominated in perivascular nerves of Meibomian gland vasculature. The close association of varicose axons with the acini of Meibomian glands indicates that nervous signals modulate meibomian secretion. Meibomian gland nerve fibers in the cynomolgus monkey appear to utilize various neuropeptides, catecholamines and nitric oxide as transmitter substances, and seem to derive from the pterygopalatine, superior cervical and trigeminal ganglion respectively.     

Patch clamp study of mouse glomus cells using a whole carotid body

Some electrophysiological characteristics of mouse glomus cells (DBA/2J strain) were investigated using an undissociated carotid body. The carotid body with major carotid arteries was placed in a recording chamber, and glomus cells were visualized with a water immersion lens combined with an infrared differential interference video camera. Patch clamp experiments revealed that voltage-gated outward current, but not inward current, was easily observed in glomus cells. Pharmacological experiments and the kinetics of the current suggest that outward current is via delayed rectifier, A type, and large conductance calcium-activated K channels. Furthermore, K current was reversibly attenuated by mild hypoxia. The results suggest electrophysiological similarities of glomus cells among the cat, the rat, and the DBA/2J mouse. The method appears useful for physiological experiments.     

Spermatogenesis in the cynomolgus monkey (Macaca fascicularis): a practical guide for routine morphological staging

The cynomolgus monkey (Macaca fascicularis) is widely used in regulatory toxicity studies. Especially in studies on male contraception, the male reproductive tract can be an important target system. The aim of the present paper is to describe a practical approach for morphological staging of spermatogenesis in routinely prepared paraffin sections. Results obtained using this approach could help to determine possible drug-related effects on spermatogenesis. As a guide to the investigators, photomicrographs of Bouin-fixed, paraffin-embedded and H&E or PAS stained sections from testis tissue are presented to illustrate the twelve successive morphological stages (cell associations) of normal spermatogenesis. Sexually immature or peripubertal monkeys sometimes are included in toxicity studies. Since the morphological features of the testes of such monkeys can be mistaken for treatment-related abnormalities, the morphologic characteristics of these testes are described and discussed briefly.     

Spontaneous unilateral renal dysplasia in a clinically healthy cynomolgus monkey (Macaca fascicularis)

Renal dysplasia is a congenital renal malformation characterized by disruption of normal renal development with asynchronous differentiation of nephrons, collecting ducts, and parenchyma and abnormal patterning of cortical and medullary tissues. The present article describes unilateral renal dysplasia discovered in a cynomolgus monkey from a routine toxicology study. The affected kidney was small and characterized by extensive interstitial fibrosis with the formation of fibromuscular collars around glomeruli and tubules, immature nephrons, and persistent mesenchyme encompassing few collecting ducts. The present case is remarkable in that there is a paucity of reports describing histopathologic findings of spontaneously occurring renal dysplasia in preclinical test species for use in large animal toxicity studies.     

Neuroexcitatory targets in the female reproductive system of the nonhuman primate (Macaca fascicularis)

Glutamate receptors (GluRs) have been implicated in brain function and pathology. Their presence in peripheral tissues suggests a vital role in the pathophysiology of various organ systems. In earlier studies, the authors reported the differential distribution of ionotropic and metabotropic GluRs in neural and nonneural peripheral tissues of the rat. In this study, they investigated the presence and the localization of the GluRs in the reproductive organs of Macaca fascicularis. The data illustrate the presence of the GluR 2/3, metabotropic glutamate receptor 2/3, kainate 2, and N-methyl-D-aspartate receptor 1 (NMDAR 1). These are localized in the different structures of the ovaries, uterine cervix, myometrium, endometrium, and inflammatory cells. Smooth muscle of the myometrium and arterioles showed strong immunolabeling with anti-GluR 2/3 and, to a lesser intensity, with the other ionotropic glutamate receptor antibodies. NMDAR 1 showed the most widespread staining in all the structures. Mast cells showed strong immunolabeling with the anti-NMDA antibody. The demonstration and the differential expression of GluRs in the female reproductive system of nonhuman primate experimental models provide first evidence suggesting excitatory signaling in these tissues.     

Analysis of hindbrain neural crest migration in the long-tailed monkey (Macaca fascicularis)

Neural crest cells make a substantial contribution to normal craniofacial development. Despite advances made in identifying migrating neural crest cells in avian embryos and, more recently, rodent embryos, knowledge of crest cell migration in primates has been limited to what was obtained by conventional morphological techniques. In order to determine the degree to which the nonhuman primate fits the mammalian pattern, we studied the features of putative neural crest cell migration in the hindbrain of the long-tailed monkey (Macaca fascicularis) embryo. Cranial crest cells were identified on the basis of reported distributional and morphological criteria as well as by immunocytochemical detection of the neural cell adhesion molecule (N-CAM) that labels a subpopulation of these cells. The persistent labeling of a sufficient number of crest cells with antibodies to N-CAM following their exit from the rostral, preotic and post-otic regions of the hindbrain facilitated tracking them along subectodermal pathways to their respective destinations in the first, second and third pharyngeal arches. Peroxidase immunocytochemistry was also employed to localize laminin and collagen-IV in neuroepithelial basement membranes. At stage 10 (8–11 somites), crest emigration occurred in areas of unfused neural folds through focal disruptions in the neuroepithelial basement membrane in both the rostral and pre-otic regions, although there was little evidence of crest migration in the post-otic hindbrain. By stage 11 (16–17 somites), the neural folds were fused (pre- and post-otic hindbrain) or in the process of fusing (rostral hindbrain), yet crest cell emigration was apparent in all three areas through discontinuities in the basement membrane. Emigration was essentially complete at stage 12 (21 somites) as indicated by nearly continuous cranial neural tube basement membranes. At this stage the pre-ganglia (trigeminal, facioacoustic and glossopharyngeal) were consistently stained with N-CAM. The current study has provided new information on mammalian neural crest in a well-established experimental model for normal and abnormal human development, including its use as a model for the retinoic acid syndrome. In this regard, the current results provide the basis for probing the mechanisms of retinoid embryopathy which may involve perturbation of hindbrain neural crest development.     

Input-output relationships of the primary face motor cortex in the monkey (Macaca fascicularis)

1. Somatosensory afferent input and its relationship with efferent output were examined in the primary face motor cortex (MI) and adjacent cerebral cortical areas. Excitatory afferent inputs were tested in a total of 1,654 single neurons recorded in awake or anesthetized monkeys (Macaca fascicularis), and output was characterized in these same monkeys by the movement and EMG responses evoked by intracortical microstimulation (ICMS) at the neuronal recording sites. 2. Most neurons in the MI area responded to light tactile stimulation of the orofacial region, especially the upper lip, lower lip, and tongue. Although contralateral afferent inputs predominated, 21% of the neurons received ipsilateral or bilateral orofacial inputs. The afferent input evoked by tactile stimulation of the upper and lower lips was represented especially at the medial border and the input from the tongue at the lateral border of MI. However, in most regions of MI between the medial and lateral borders, an intermingling of tactile inputs from different orofacial areas occurred. Multiple representation of tactile input from the same orofacial area was found in several, often quite separate, intracortical sites in MI. 3. Only a small proportion of the MI neurons could be activated by the deep stimuli used (e.g., stretch and pressure applied to muscle, passive jaw movement, low-intensity stimulation of hypoglossal nerve) from the orofacial region. Those neurons which did respond to these low-threshold deep inputs were not clearly segregated from those which responded to tactile input, although most of the neurons receiving deep input were located in the rostral part of MI. 4. A somatotopic pattern of representation of orofacial tactile input was more obvious in the primary face somatosensory cortex (SI). At the medial border of SI, the periorbital area was represented, then followed laterally in sequence the tactile representation of the upper lip, lower lip, and intraoral area. Contralateral afferent inputs predominated, but as in MI, a considerable proportion of SI neurons received ipsilateral or bilateral orofacial inputs. Few neurons in the region explored (areas 3b, 1, and 2) responded to deep orofacial stimuli. 5. Tactile input also dominated the input patterns of neurons in the premotor cortex (PM). Most neurons received ipsilateral or bilateral orofacial afferent inputs and no clear somatotopic pattern was noted. Several PM neurons were also activated by visual stimuli. 6. Muscle twitches evoked by ICMS were limited to MI.(ABSTRACT TRUNCATED AT 400 WORDS)     

Features of cortically evoked swallowing in the awake primate (Macaca fascicularis).

Although the cerebral cortex has been implicated in the control of swallowing, the output organization of the cortical swallowing representation, and features of cortically evoked swallowing, remain unclear. The present study defined the output features of the primate "cortical swallowing representation" with intracortical microstimulation (ICMS) applied within the lateral sensorimotor cortex. In four hemispheres of two awake monkeys, microelectrode penetrations were made at 5 mm deep to the cortical surface corresponding to both the white matter underlying the CMA and the frontal operculum; EMG patterns of swallows elicited from these four cortical regions showed some statistically significant differences. Whereas swallowing ONLY was evoked at some sites, particularly within the deep cortical area, swallowing was more frequently evoked together with other orofacial responses including rhythmic jaw movements. Increasing ICMS intensity increased the magnitude, and decreased the latency, of the swallow-related EMG burst in the genioglossus muscle at some sites. These findings suggest that a number of distinct cortical foci may participate in the initiation and modulation of the swallowing synergy as well as in integrating the swallow within the masticatory sequence.     

Absence of self-recognition in a monkey (Macaca fascicularis) following prolonged exposure to a mirror.

To date only chimpanzees, orangutans, and humans have been found capable of recognizing themselves in mirrors. In an attempt to provide a more definitive test of the capacity for self-recognition in monkeys. I gave a preadolescent crab-eating macaque 2400 hr of mirror exposure. However, patterns of self-directed behavior never developed and a more explicit test of self-recognition yielded negative results. The data indicate possible differences between great apes and monkeys in self-awareness.