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PubMed1976

Induction of liver tumors by aflatoxin B1 in the tree shrew (Tupaia glis), a nonhuman primate.

The epidemiological studies suggest that aflatoxins, the toxic metabolites of the ubiquitous mold Aspergillus flavus, may play a significant role in the evolution of hepatocellular carcinoma in man in certain geographic areas of the world. To ascertain their carcinogenicity in nonhuman primates, we have administered highly purified aflatoxin B1, intermittently in the diet at 2 ppm, to 10 female and 8 male tree shrews. The tree shrew (Tupaia glis) is a nonhuman primate occurring throughout Southeast Asia which can be reared easily in captivity. Of 12 animals that survived, 6 of 6 female (100%) and 3 of 6 male (50%) tree shrews developed hepatocellular carcinomas between 74 and 172 weeks after the beginning of the experiment. None of the 8 control animals developed liver cancers. The estimated total amount of aflatoxin B1 consumed by these animals ranged from 24 to 66 mg. The development of liver tumors did not follow a specific pattern; considerable variation in hepatocellular responses to aflatoxin B1 was noted in these animals. In 2 tree shrews, the liver tumors were associated with severe post necrotic scarring; in the other 7 tumor-bearing livers, only mild to moderate portal fibrosis was encountered. This individual variation in hepatocellular response and in the amount of aflatoxin B1 required to induce hepatocellular carcinomas is attributed to inherent differences in the susceptibility within a given species of outbred animals and suggests extreme caution in proposing the "permissible" or "safe" levels of contamination of carcinogens in the food-stuffs.

Aflatoxins↗
PubMed1991

The occurrence of Centrorhynchus (Acanthocephala) in shrews (Sorex araneus and Sorex minutus) in the United Kingdom.

Encysted acanthocephalans belonging to the genus Centrorhynchus were found in the body cavities of Sorex araneus (common shrew) and Sorex minutus (pygmy shrew) from Boxworth, Cambridgeshire, U.K. Fifty percent of the male S. araneus and 67% of the male S. minutus examined were found to be infected, with the mean intensity (+/-SD) being 54.3 +/- 91.3 and 14.7 +/- 18.4, respectively. The species of Centrorhynchus in the shrews may be Centrorhynchus aluconis, which is distributed widely in tawny owls, Strix aluco, in the United Kingdom. Shrews appear to serve as paratenic hosts for C. aluconis.

Acanthocephala↗
PubMed1985

Ultrastructure of the stomach of the small short-tailed shrew, Blarina brevicauda c.

The normal gastric ultrastructure has been characterized for the small short-tailed shrew, Blarina brevicauda c., which is a primitive eutherian and one of the smallest living mammals with extraordinarily high metabolic rate. In general the cell types present and cytologic character of gastric mucosal, submucosal, and muscularis cells were similar to that reported for other more advanced small mammalian species. Chief cells, endocrine cells, and lamina proprial elements were morphologically identical to their counterpart in rats, ferrets and other small carnivores. Distinctive cytologic features in this species of shrew included the scanty monolayer or small number of mucous granules in the simple columnar surface epithelial cells of the mucosa, and the thin elongated shape of their microvilli. Dense bodies were absent in the parietal cell mitochondria of the shrew, though usually abundant in other mammalian parietal cells. Our data indicate few morphologic specializations in the shrew stomach which can be correlated with their high rate of food assimilation and metabolic demands, though future studies of mucosal biochemistry and lower gut morphology may reveal such adaptations.

Animals↗
PubMedDate not supplied

Fecal pellets from a commensal shrew (Suncus murinus) and a house gecko (Gekkonidae).

Examination of excreta pellets from commensal shrew (Suncus murinus) and tropical house geckos (Gekkonidae) showed several characteristics that were useful in distinguishing these pellets from those of commensal rodents. Commensal shrew pellets contained a large number of embedded insect fragments but no embedded hairs. Each shrew pellet was associated with a distinctive circular stain on the floor or container surface where it was found. Gecko pellets were composed entirely of tightly packed insect fragments with no intervening matrix. In contrast to both shrew and rodent pellets, there was no surface mucous coating. A small white body containing uric acid adhered to one end of each gecko pellet.

Animals↗
PubMed1980

The occurrence of salmonellae in rodent, shrew, cockroach and ant.

The occurrence of salmonellae in common house-pests viz. rats, house-mice, shrews, cockroaches and ants was investigated during the period of Jan. 1976 to July 1979. Of 767 samples examined, 43 yielded different Salmonella serotypes. The isolation of salmonellae was made from 16 of 254 rats, 11 of 109 house-mice, 11 of 104 shrews, 3 of 270 cockroaches and 2 of 30 ants. The different Salmonella serotypes isolated included S. saint-paul, S. bareilly, S. newport, S. weltevreden, S. enteritidis, S. typhimurium, S. hvittingfoss, S. anatum, S. metopeni, S. waycross and S. paratyphi B. One shrew yielded three different serotypes of salmonellae, while dual infection was detected in three shrews and one rat.

Animals↗
PubMed1995

Experimental models for carcinogenesis in the house musk shrew, Suncus murinus, Insectivora.

Animal carcinogenicity studies have mainly been performed on rodents. From the phylogenetic point of view, animals closer to humans must be included in these studies. Insectivora are considered to be the most primitive placental mammals and much closer to the early primates than rodents. Among the insectivora, the house musk shrew (Suncus murinus, family Soracidae), has been bred under laboratory condition. This animal is small having a short life span, and a comparatively low incidence of spontaneous tumor provides a useful animal model for tumor induction studies. We have examined the carcinogenicity of several chemicals known to produce tumors in rodents and found shrews, in general, to be sensitive to these chemicals but often showed different targets compared to rodents, and some chemicals tested were demonstrated not to be carcinogenic. Here we describe the carcinogenic studies performed in our laboratory and review other works including the occurrence of spontaneous tumors in shrews. Shrew carcinogenesis may fill up the gap of knowledge existing between the rodents and human beings.

Animals↗
PubMed1996

Ticks and fleas of shrews in Appalachian Georgia and North Carolina.

Ticks (Acari: Ixodidae) and fleas (Insecta: Siphonaptera) were recovered from 8 smoky shrews, Sorex fumeus Miller, and 9 northern short-tailed shrews, Blarina brevicauda (Say), trapped at elevations of 720-1,310 m in Macon and Jackson counties in western North Carolina and Union County in northern Georgia from April 1994 to August 1995. The ticks Ixodes angustus Neumann and Ixodes woodi Bishopp, and the flea Corrodopsylla curvata (Rothschild), were recovered from smoky shrews. The same 2 tick species, in addition to the fleas, Ctenophthalmus pseudagyrtes Baker and Doratopsylla blarinae Fox, were recovered from northern short-tailed shrews. New state records for I. angustus from Georgia and I. woodi from North Carolina are established.

Animals↗
PubMed1996

Distribution of alpha- and beta-subunits of glycoprotein hormones in thyrogonadotroph in the anterior pituitary cells of the musk shrew (Suncus murinus).

In order to examine the distribution pattern of alpha- and beta-subunits of glycoprotein hormones in small and large granules in the thyrogonadotrophs of the musk shrew, we used an antiserum against a synthesized peptide consisting of the sequence 37-53 of the rat alpha-subunit, which is highly conservative among several mammalian species, and also antisera to LH beta, FSH beta and TSH beta. Both alpha- and LH beta-subunits were colocalized in what appeared at the light-microscopic level to be the same cells, and the population ratio of alpha- and LH beta-subunit immuno-reactive cells was almost equal within each group of animals. In addition, we also demonstrated thyrogonadotrophs in the infant musk shrew as well as in the adult. Concerning small and large granules in thyrogonadotrophs of the musk shrew, we could observed small granules immunoreactive for only the alpha-subunit, for the LH beta-subunit and for both the alpha- and LH beta-subunits; while only the LH beta-subunit was observed in the large granules and the alpha-subunit was absent. Consequently, we propose that the large granules observed in the thyrogonadotrophs of the musk shrew may be storage sites for beta-subunits and are not secretory-type granules.

Aging↗
PubMed2003

The visual pulvinar in tree shrews II. Projections of four nuclei to areas of visual cortex.

Patterns of thalamocortical connections were related to architectonically defined subdivisions of the pulvinar complex and the dorsolateral geniculate nucleus (LGN) in tree shrews (Tupaia belangeri). Tree shrews are of special interest because they are considered close relatives of primates, and they have a highly developed visual system. Several distinguishable tracers were injected within and across cortical visual areas in individual tree shrews in order to reveal retinotopic patterns and cortical targets of subdivisions of the pulvinar. The results indicate that each of the three architectonic regions of the pulvinar has a distinctive pattern of cortical connections and that one of these divisions is further divided into two regions with different patterns of connections. Two of the pulvinar nuclei have similar retinotopic patterns of projections to caudal visual cortex. The large central nucleus of the pulvinar (Pc) projects to the first and second visual areas, V1 and V2, and an adjoining temporal dorsal area (TD) in retinotopic patterns indicating that the upper visual quadrant is represented dorsal to the lower quadrant in Pc. The smaller ventral nucleus (Pv) which stains darkly for the Cat-301 antigen, projects to these same cortical areas, with a retinotopic pattern. Pv also projects to a temporal anterior area, TA. The dorsal nucleus (Pd), which densely expresses AChE, projects to posterior and ventral areas of temporal extrastriate cortex, areas TP and TPI. A posterior nucleus, Pp, projects to anterior areas TAL and TI, of the temporal lobe, as well as TPI. Injections in different cortical areas as much as 6 mm apart labeled overlapping zones in Pp and double-labeled some cells. These results indicate that the visual pulvinar of tree shrews contains at least four functionally distinct subdivisions, or nuclei. In addition, the cortical injections revealed that the LGN projects topographically and densely to V1 and that a significant number of LGN neurons project to V2 and TD.

Acetylcholinesterase↗
PubMed2006

Organization of frontoparietal cortex in the tree shrew (Tupaia belangeri). I. Architecture, microelectrode maps, and corticospinal connections.

Despite extensive investigation of the motor cortex of primates, little is known about the organization of motor cortex in tree shrews, one of their closest living relatives. We investigated the organization of frontoparietal cortex in Belanger's tree shrews (Tupaia belangeri) by using intracortical microstimulation (ICMS), corticospinal tracing, and detailed histological analysis. The results provide evidence for the subdivision of tree shrew frontoparietal cortex into seven distinct areas (five are newly identified), including two motor fields (M1 and M2) and five somatosensory fields (3a, 3b, S2, PV, and SC). The types of movements evoked in M1 and M2 were similar, but M2 required higher currents to elicit movements and had few connections to the cervical spinal cord and distinctive cyto- and immunoarchitecture. The borders between M1 and the anterior somatosensory regions (3a and 3b) were identified primarily from histological analysis, because thresholds were similar between these regions, and differences in corticospinal neuron distribution were subtle. The caudal (SC) and lateral (S2 and PV) somatosensory fields were identified based on differences in architecture and distribution of corticospinal neurons. Myelin-dense modules were identified in lateral cortex, in the expected location of the oral, forelimb, and hindlimb representations of S2, and possibly PV. Evidence for a complex primate-like array of motor fields is lacking in tree shrews, but their motor cortex shares a number of basic features with that of primates, which are not found in more distantly related species, such as rats.

Animals↗
PubMed1994

Prevention of collagen crosslinking increases form-deprivation myopia in tree shrew.

To examine whether collagen crosslinking is important for the regulation of refractive development, tree shrews were treated with agents that block collagen crosslinking [beta-aminoproprionitrile (beta-APN), or D-penicillamine (DPA)] and underwent monocular deprivation (MD) of form vision by eyelid closure to induce myopia. MD began on the first day of visual exposure and continued for 75 days. After 15-20 days of visual exposure, daily intraperitoneal injections of beta-APN (beta-APN MD animals, n = 5) or DPA (DPA MD animals, n = 5) were administered for 17-21 days. beta-APN open animals (n = 5) received the same injection schedule, but both eyes remained open. Saline MD animals (n = 5) received i.p. saline and MD. At 75 days of visual exposure, the MD eyes of beta-APN treated tree shrews were highly myopic (-23.6 +/- 3.3 D) in comparison to their open control eyes. This was markedly greater than the difference in saline MD animals (-11.0 +/- 0.8 D). DPA MD animals showed a relative myopia of -14.3 +/- 2.2 D. The structural correlate of the myopia, elongation of the vitreous chamber in the deprived eyes relative to the control eyes, was significantly greater in the beta-APN MD animals 0.53 +/- 0.03 mm, which was not significantly different from the saline MD group. Thinning of the posterior sclera, but not the cornea, was observed in the deprived eyes of beta-APN treated tree shrews, along with a tessellated appearance to the fundus. The eyes of the beta-APN open animals showed no significant differences from normal. Beta-APN MD and DPA MD treated chickens did not develop greater myopia or vitreous chamber elongation than standard MD chickens. The selective effect of the lathyritic agents on the deprived eyes in tree shrew suggests that collagen crosslinking interacts, in the mammalian sclera, with a retinally-derived signal to regulate the elongation of the eye in myopia.

Aminopropionitrile↗
PubMed2005

Areal specialization of pyramidal cell structure in the visual cortex of the tree shrew: a new twist revealed in the evolution of cortical circuitry.

Cortical pyramidal cells, while having a characteristic morphology, show marked phenotypic variation in primates. Differences have been reported in their size, branching structure and spine density between cortical areas. In particular, there is a systematic increase in the complexity of the structure of pyramidal cells with anterior progression through occipito-temporal cortical visual areas. These differences reflect area-specific specializations in cortical circuitry, which are believed to be important for visual processing. However, it remains unknown as to whether these regional specializations in pyramidal cell structure are restricted to primates. Here we investigated pyramidal cell structure in the visual cortex of the tree shrew, including the primary (V1), second (V2) and temporal dorsal (TD) areas. As in primates, there was a trend for more complex branching structure with anterior progression through visual areas in the tree shrew. However, contrary to the trend reported in primates, cells in the tree shrew tended to become smaller with anterior progression through V1, V2 and TD. In addition, pyramidal cells in V1 of the tree shrew are more than twice as spinous as those in primates. These data suggest that variables that shape the structure of adult cortical pyramidal cells differ among species.

Animals↗
PubMed2005

Mossy cells and different subpopulations of pyramidal neurons are immunoreactive for cocaine- and amphetamine-regulated transcript peptide in the hippocampal formation of non-human primates and tree shrew (Tupaia belangeri).

Cocaine- and amphetamine-regulated transcript peptide mRNA was discovered in the rat striatum following cocaine and amphetamine administration. Since both psychostimulants elicit memory-related effects, localization of cocaine- and amphetamine-regulated transcript peptide in the hippocampal formation may have functional importance. Previous studies demonstrated different cellular localizations of cocaine- and amphetamine-regulated transcript peptide in humans and in rodents. Mossy cells were cocaine- and amphetamine-regulated transcript-positive in the human dentate gyrus, whereas granule cells contained this peptide in the rat. In the present study, the localization of cocaine- and amphetamine-regulated transcript peptide was examined using immunohistochemistry in the hippocampal formation of the rhesus monkey (Macaca mulatta), the common marmoset monkey (Callithrix jacchus) and in the tree shrew (Tupaia belangeri). In these species principal neurons of the hippocampal formation were cocaine- and amphetamine-regulated transcript-immunoreactive. In both monkeys and tree shrews, mossy cells of the hilus were cocaine- and amphetamine-regulated transcript-positive whereas granule cells of the dentate gyrus were cocaine- and amphetamine-regulated transcript-negative. The dense cocaine- and amphetamine-regulated transcript-immunoreactive axonal plexus of the associational pathway outlined the inner one-third of the dentate molecular layer. In the hippocampus of the tree shrew and marmoset monkey, a subset of CA3 pyramidal cells were cocaine- and amphetamine-regulated transcript-immunoreactive. In the marmoset monkey, cocaine- and amphetamine-regulated transcript labeling was found only in layer V pyramidal cells of the entorhinal cortex, while in the rhesus monkey, pyramidal cells of layers II and III were cocaine- and amphetamine-regulated transcript-immunopositive. Our results show that cocaine- and amphetamine-regulated transcript positive neurons in the dentate gyrus of non-human primates are similar to that of the human. Furthermore, in the hippocampal formation of the tree shrew similar cocaine- and amphetamine-regulated transcript-immunoreactive cell-types were observed as in monkeys, supporting their evolutionary relationship with primates. Mossy cells and granule cells are members of a mutual excitatory intrahippocampal circuitry, therefore cocaine- and amphetamine-regulated transcript-immunoreactivity of these neurons in primates and rodents suggests that psychostimulants cocaine and amphetamine may induce memory-related effects at different points of the same excitatory circuitry in the hippocampal formation.

Animals↗
PubMed2002

Social stress in tree shrews: effects on physiology, brain function, and behavior of subordinate individuals.

Social stress is known to be involved in the etiology of central nervous disorders such as depression. In recent years, animal models have been developed that use chronic stress to induce neuroendocrine and central nervous changes that might be similar to those occurring in the course of the development of depressive disorders. The present review gives a summary of observations made in the tree shrew chronic social stress model. During periods of daily social stress, male tree shrews develop symptoms that are known from many depressed patients such as persistent hyperactivities of both the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system, disturbances in sleeping patterns, and reduced motor activity. Moreover, various physiological parameters indicate an acceleration of the over all metabolic rate in socially stressed tree shrews. Some of these parameters can be renormalized by antidepressants thus supporting the view of the tree shrew social stress paradigm as model for major depression. In the brains of socially stressed animals, monoamine receptors show dynamic changes that reflect adaptation to the persistent monoaminergic hyperactivity during periods of chronic stress. In addition to the changes in neurotransmitter systems, there are structural changes in neurons, e.g., retraction of the dendrites of hippocampal pyramidal neurons. Together, these processes are suggested as a cause of behavioral alterations that can be counteracted by antidepressants in this naturalistic social stress model.

Animals↗
PubMed1999

Mapping of cytoskeletal components in the hippocampal formation of the tree shrew (Tupaia belangeri).

The distribution of the major cytoskeletal components in frontal cryosections of the hippocampal formation of adult male tree shrews (Tupaia belangeri) was immunohistochemically investigated by using commercially available antibodies. Actin-immunolabeling was evident in all layers of the dentate gyrus as well as in the regio superior (CA1) and the regio inferior (CA3). Neurofilament 160 was detected only in the molecular layer of the dentate gyrus and in the axons of the granule cells (mossy fibers). For beta-tubulin, the microtubule associated proteins (MAPs) MAP2AB, MAP2ABC and Tau, immunoreactivity was evident within the granule cells and within the somatodendritic compartment of pyramidal neurons. Granule cells and the somata of the pyramidal neurons were intensely labeled for kinesin. Our findings show the elaborate expression of cytoskeletal proteins in the hippocampal formation of the tree shrew, relatively similar to what is seen in other species but with also some important differences, such as the immunonegativity of the axonal compartment for Tau in the tree shrew, which is contrary to what we see in the mouse (unpublished data). These findings provide useful insights regarding the organization of the hippocampal formation of the tree shrew and are fundamental for further research in this field.

Actins↗
PubMedDate not supplied

Subdivisions of the visual system labeled with the Cat-301 antibody in tree shrews.

The monoclonal antibody Cat-301 was used to stain neurons and neuropil in the visual thalamus and cortex of tree shrews--small, highly visual mammals that are closely related to primates. Previously, this antibody has been found to label neurons associated with the Y-cell stream of processing in cats and the magnocellular or M-cell stream in macaque monkeys. In tree shrews, the antibody selectively labeled layers 1, 2, 4, and 5 of the dorsal lateral geniculate nucleus, layers that are likely to contain neurons previously classified as Y-cells. Of the two layers that contain W-cells, layer 3 was unlabeled and layer 6 was lightly labeled. In area 17, layer 3c was densely stained, as in cats and macaque monkeys. The external half of layer 5 was also densely stained, in contrast to cats where the internal half of layer 5 is stained and macaques where layer 5 is sparsely stained. Area 18 was characterized by dense, uniform staining of inner layer 3 and outer layer 5, but no pattern of alternating light and dense bands crossed the width of area 18 as in macaques. Dense labeling of these same sublayers occurred in cortical areas TA and TD just lateral to area 18. Area TD may be the homologue of area MT of primates, which also stains densely with Cat-301 in macaques. These results indicate that Cat-301 differentially labels layers and areas in the visual system of tree shrews, and raise intriguing issues of comparison among tree shrews, primates, and cats.

Animals↗
PubMed1997

Beta-adrenoceptors in the tree shrew brain. I. Distribution and characterization of [125I]iodocyanopindolol binding sites.

1. The number and distribution pattern of beta-adrenergic receptors in the brain have been reported to be species specific. The aim of the present study was to describe binding of the beta-adrenoceptor ligand [125I]iodocyanopindolol in the brain of the tree shrew (Tupaia belangeri), a species which provides an appropriate model for studies of psychosocial stress and its consequences on central nervous processes. 2. 125I-Iodocyanopindolol (125ICYP) labeling revealed a high degree of nonspecific binding, which was due mainly to interactions of this ligand with serotonin binding sites. For a quantitative evaluation of beta 1- and beta 2-adrenoceptors, serotonin binding sites had to be blocked by 100 microM 5HT. 3. Binding of the radioligand to beta 1- and beta 2-adrenoceptors was characterized using the beta 1-specific antagonist CGP20712A and the beta 2-specific antagonist ICI118.551. beta 1-adrenoceptor binding is present in the whole brain, revealing low receptor numbers in most brain regions (up to 1.5 to 2.7 fmol/mg). A slight enrichment was observed in cortical areas (lateral orbital cortex: 4.0 +/- 0.7 fmol/mg) and in the cerebellar molecular layer (8.7 +/- 1.0 fmol/mg). 4. Competition experiments demonstrated high- and low-affinity binding sites with considerable variations in Ki values for CGP20712A, showing that various affinity states of beta 1-adrenoceptors are present in the brain (Ki: 0.61 nM to 67.1 microM). In the hippocampus, only low-affinity beta 1-adrenoceptors were detected (Ki: 1.3 +/- 0.2 microM). Since it is known that 125ICYP labels not only membrane bound but also internalized beta-adrenoceptors, it can be assumed that the large population of the low-affinity sites represents internalized receptors which may be abundant due to a high sequestration rate. 5. High numbers of beta 2-adrenoceptors are present in only a few brain structures of tree shrews (external layer of the olfactory bulb, 15.8 +/- 2.0 fmol/mg; claustrum, 19.3 +/- 1.5 fmol/mg; anteroventral thalamic nucleus, 19.4 +/- 1.5 fmol/mg; cerebellar molecular layer, 55.0 +/- 4.3 fmol/mg). Also for this class of beta-adrenoceptors, high- and low-affinity binding sites for the beta 2-selective antagonist ICI118.551 were observed, indicating that 125ICYP labels membrane bound and internalized beta 2-adrenoceptors. Only in the cerebellar molecular layer was a high percentage of high-affinity beta 2-adrenoceptors detected (Ki for ICI118.551 was 1.8 +/- 0.3 nM for 90% of the receptors). 6. In conclusion, beta 1- and beta 2-adrenoceptor binding can be localized and quantified by in vitro receptor autoradiography in the brains of tree shrews when serotonergic binding sites are blocked. Modulatory effects of long-term psychosocial conflict on the central nervous beta-adrenoceptor system in male tree shrews are described in the following paper.

Adrenergic beta-Antagonists↗
PubMed2002

The chronic psychosocial stress paradigm in male tree shrews: evaluation of a novel animal model for depressive disorders.

To improve our knowledge of the causal mechanisms of stress-related disorders such as depression, we need animal models that mirror the situation in patients. One promising model is the chronic psychosocial stress paradigm in male tree shrews, which is based on the territorial behaviour of these animals that can be used to establish naturally occurring challenging situations under experimental control in the laboratory. Co-existence of two males in visual and olfactory contact leads to a stable dominant-subordinate relationship, with subordinates showing distinct stress-induced behavioural and neuroendocrine alterations that are comparable to the symptoms observed during episodes of depression in patients such as constantly elevated circulating glucocorticoid hormones due to a chronic hyperactivity of the hypothalamic-pituitary-adrenal axis. To elucidate whether the chronic psychosocial stress model in tree shrews besides its "face validity" for depression also has "predictive validity", we treated subordinate tree shrews with the tricyclic antidepressant clomipramine and found a time-dependent restoration of both endocrine and behavioural parameters. In contrast, the anxiolytic diazepam was ineffective. Although the chronic psychosocial stress model in tree shrews requires further validation, it has sufficient face, predictive, and construct validity to become an interesting non-rodent model for research on the etiology and pathophysiology of depression.

Animals↗