Prolonged secretion of cortisol as a possible mechanism underlying stress and depressive behaviour.

Stress is associated with the onset of depressive episodes, and cortisol hypersecretion is considered a biological risk factor of depression. However, the possible mechanisms underlying stress, cortisol and depressive behaviours are inconsistent in the literature. This study examined the interrelationships among stress, cortisol and observed depressive behaviours in female rhesus macaques for the first time and explored the possible mechanism underlying stress and depressive behaviour. Female monkeys were video-recorded, and the frequencies of life events and the duration of huddling were analysed to measure stress and depressive behaviour. Hair samples were used to measure chronic cortisol levels, and the interactions between stress and cortisol in the development of depressive behaviour were further evaluated. Significant correlations were found between stress and depressive behaviour measures and between cortisol levels and depressive behaviour. Stress was positively correlated with cortisol levels, and these two factors interacted with each other to predict the monkeys' depressive behaviours. This finding extends the current understanding of stress/cortisol interactions in depression, especially pertaining to females.

Early adversity contributes to chronic stress induced depression-like behavior in adolescent male rhesus monkeys.

Chronic stress is an important cause for depression. However, not everyone who is exposed to chronic stress will develop depression. Our previous studies demonstrated that early adversity can cause lasting changes in adolescent rhesus monkeys, but depressive symptoms have not been observed. Compared to adults, it is still unknown that whether adolescent rhesus monkeys experiencing early adversity are more likely to develop depressive symptoms. In this study, we investigated the long term relationship between early adversity, chronic stress and adolescent depression for the first time. Eight male rhesus monkeys were reared in maternal separation (MS) or mother-reared (MR) conditions. All of them went through unpredictable chronic stress for two months at their age four. The stressors included space restriction, intimidation, long illumination and fasting. Behavioral and physiological data were collected during the experiment. The results showed that, compared with the MR group, the locomotor activity of MS group was significantly decreased after one month of chronic stress while huddling up and stereotypical behaviors were significantly increased. Moreover, this trend continued and even worsened at the second month. Significantly higher hair cortisol levels and lower body weight were observed in MS group after two months of stress. These results indicate that early adversity is one of the environmental factors which can increase the susceptibility of depression when experiencing chronic stress in the later life. This will further clarify the important roles of early environmental factors in the development of adolescent depression and children rearing conditions should receive more attention.

Diverse interleukin-7 mRNA transcripts in Chinese tree shrew (Tupaia belangeri chinensis).

Interleukin-7 (IL7) is a pleiotropic cytokine that is actively involved in the immune system. The Chinese tree shrew (Tupaia belangeri chinensis) has been proposed as an alternative experimental animal to primates in biomedical research. However, there is a lack of biological knowledge about the immune system of the tree shrew. In this study, we cloned the IL7 gene (tIL7) in the Chinese tree shrew and quantified the expression of mRNA transcripts in eight tissues (heart, liver, spleen, lung, kidney, intestine, skeletal muscle and brain) from 20 individuals. Eleven tIL7 mRNA transcripts were identified in different tissues. The canonical form (tIL7c) had a length of 1817 bp and encoded a predicted gene product with 177 amino acids. Phylogenetic analyses based on the amino acid sequences revealed a considerably large genetic difference between tree shrew and human. Quantification of mRNA expression of transcripts tIL7c, tIL7-sv1, tIL7-sv2 and tIL7-sv3 showed that these transcripts were expressed in all tissues, albeit the expression levels varied in different tissues. Transcripts tIL7c, tIL7-sv1, and tIL7-sv2 had the lowest expression in brain, and tIL7-sv3 had a dramatically high mRNA expression in skeletal muscle and heart. The mRNA expression levels of tIL7c and tIL7-sv1 were significantly increased upon ploy(I:C) stimulation in tree shrew primary renal cells. As with human full-length IL7, tIL7c, tIL7-sv1, tIL7-sv2 and tIL7-sv3 showed similar a subcellular localization pattern. Our results identified diverse tIL7 transcripts in the Chinese tree shrew, which may play a potential role in modulating IL7-regulated biological effects.

[Tree shrews under the spot light: emerging model of human diseases].

Animal models are indispensible in biomedical research and have made tremendous contributions to answer fundamental questions on human biology, disease mechanisms, and to the development of new drugs and diagnostic tools. Due to the limitations of rodent models in translational medicine, tree shrews (Tupaia belangeri chinensis), the closest relative of primates, have attracted increasing attention in modeling human diseases and therapeutic responses. Here we discuss the recent progress in tree shrew biology and the development of tree shrews as human disease models including infectious diseases, metabolic diseases, neurological and psychiatric diseases, and cancers. Meanwhile, the current problems and future perspectives of the tree shrew model are explored.

[Measurement and analysis of hematology and blood chemistry parameters in northern pig-tailed macaques (Macaca leonina)].

The pig-tailed macaque is an important non-human primate experimental animal model that has been widely used in the research of AIDS and other diseases. Pig-tailed macaques include Mentawai macaques (Macaca pagensis), Sunda pig-tailed macaques (M. nemestrina) and northern pig-tailed macaques (M. leonina). Northern pig-tailed macaques inhabit China and surrounding Southeast Asia countries. To our knowledge, no reports have been published regarding the hematology and blood chemistry parameters of northern pig-tailed macaques, which are important for the objective evaluation of experimental results. We measured and analyzed 18 hematology parameters and 13 blood chemistry parameters in juvenile (aged 2-4 years) and adult (aged 5-10 years) northern pig-tailed macaques. We found that red blood cells, hemoglobin and alkaline phosphatase values were lower in female macaques than male macaques in both juvenile and adult groups. White blood cells, lymphocyte, monocytes, platelet distribution width, cholesterol, aspartate aminotransferase and alkaline phosphatase values were higher in juvenile macaques than adult macaques, while creatinine and triglycerides values were lower in juvenile macaques. Mean corpuscular hemoglobin and creatinine values were positively correlated with weight in juvenile groups. In adult groups, mean corpuscular hemoglobin, percentage of granulocyte, hemoglobin and creatinine were also positively correlated with weight, and lymphocyte, percentage of lymphocyte, red cell distribution width, aspartate aminotransferase and cholesterol values were negatively correlated with weight. The results suggest that age, gender and weight of northern pig-tailed macaques affected their hematology and blood chemistry parameters. This hematological and blood chemistry study has great significance in biomedical research and animal models using northern pig-tailed macaque as an experimental animal.

Basal physiological parameters in domesticated tree shrews (Tupaia belangeri chinensis).

Establishing non-human primate models of human diseases is an efficient way to narrow the large gap between basic studies and translational medicine. Multifold advantages such as simplicity of breeding, low cost of feeding and facility of operating make the tree shrew an ideal non-human primate model proxy. Additional features like vulnerability to stress and spontaneous diabetic characteristics also indicate that the tree shrew could be a potential new animal model of human diseases. However, basal physiological indexes of tree shrew, especially those related to human disease, have not been systematically reported. Accordingly, we established important basal physiological indexes of domesticated tree shrews including several factors: (1) body weight, (2) core body temperature and rhythm, (3) diet metabolism, (4) locomotor rhythm, (5) electroencephalogram, (6) glycometabolism and (7) serum and urinary hormone level and urinary cortisol rhythm. We compared the physiological parameters of domesticated tree shrew with that of rats and macaques. Results showed that (a) the core body temperature of the tree shrew was 39.59±0.05 ℃, which was higher than that of rats and macaques; (b) Compared with wild tree shrews, with two activity peaks, domesticated tree shrews had only one activity peak from 17:30 to 19:30; (c) Compared with rats, tree shrews had poor carbohydrate metabolism ability; and (d) Urinary cortisol rhythm indicated there were two peaks at 8:00 and 17:00 in domesticated tree shrews, which matched activity peaks in wild tree shrews. These results provided basal physiological indexes for domesticated tree shrews and laid an important foundation for diabetes and stress-related disease models established on tree shrews.

[Sero-epidemiology of six viruses natural infection in Tupaia belangeri chinensis].

Tupaia (Tupaia belangeris chinensis, tree shrew) as a new experiment animal in medicine are non-rodent, small animals and close to primates in evolution. Experimental animals infected with viruses will affect the animal's health, interference experiment, and even endanger the operator's safety. Therefore, the viral infection in experimental animals has long been considered an important part of quality control. Lack of clearer viral natural infection information on the T. belangeris limits its use. Six viruses infection in 272 wild capture and artificial breeding Tupaia were investigated in this study. All serum samples were detected for the hepatitis B virus surface antigen, the total antibodies of HCV, hepatitis E virus (HEV), adenovirus (ADV), herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) by ELISA. The results showed that anti-HCV antibody and anti-HEV, ADV, HSV-1 IgG antibodies were negative, only one sample was positive of anti-HSV-2 IgG.. Three samples were positive in the primary ELISA detection of HBV surface antigen, but two pairs of semi-quantitative detection of hepatitis B and further recognized as negative. The results implied that antigen or antibody-positive results appeared in the hepatitis serological test is not accurate enough and confirmation by other virological indicators is necessary. Tupaia breeding herd should be screened for HSV-2 in order to prevent and control the virus infection.

Genetic diversity and matrilineal structure in Chinese tree shrews inhabiting Kunming, China.

Due to their special phylogenetic position in the Euarchontoglires and close affinity to primates, tree shrews have been proposed as an alternative experimental animal to primates in biomedical research. However, the population genetic structure of tree shrews has largely remained unknown and this has hindered the development of tree shrew breeding and selection. Here we sampled 80 Chinese tree shrews (Tupaia belangeri chinensis) in Kunming, China, and analyzed partial mtDNA control region sequence variation. Based on our samples and two published sequences from northern tree shrews (T. belangeri), we identified 29 substitutions in the mtDNA control region fragment (~604 bp) across 82 individuals and defined 13 haplotypes. Seventeen samples were selected for sequencing of the cytochrome b (Cyt b; 1134 bp) gene based on control region sequence variation and were analyzed in combination with 34 published sequences to solidify the phylogenetic pattern obtained from control region data. Overall, tree shrews from Kunming have high genetic diversity and present a remarkable long genetic distance to the two reported northern tree shrews outside China. Our results provide some caution when using tree shrews to establish animal models because of this apparent genetic difference. In addition, the high genetic diversity of Chinese tree shrews inhabiting Kunming suggests that systematic genetic investigations should be conducted before establishing an inbred strain for medical and biological research.