Kidney cell culture Macaca fascicularis as a candidate for vaccine development and in vitro model.

BACKGROUND: Cell culture is the proliferation of a cell population in vitro by isolating from the original tissue or growing from existing ones. One essential source is the monkey kidney cell cultures which have an essential role in biomedical study. This is due to the significant homology between the human and macaque genomes making these useful for cultivating human viruses, especially enteroviruses, and growing vaccines. METHODS: This study developed cell cultures derived from the kidney of Macaca fascicularis (Mf) and validated its gene expression. RESULTS: The primary cultures were successfully subcultured up to six passages, grew as monolayers, and exhibited epithelial-like morphology. The cultured cells remained heterogeneous in phenotype and they expressed CD155 and CD46 as viral receptors, cell morphology (CD24, endosialin, and vWF), proliferation, also apoptosis markers (Ki67 and p53). CONCLUSIONS: These results indicated that the cell cultures can be used as in vitro model cells for vaccine development and bioactive compound.

Welfare assessment of slow loris (Nycticebus spp.) at an Indonesian primate rehabilitation center: Development and validation of body condition score.

Body condition scoring (BCS) assessment can reflect animal welfare status and help the veterinarian to make a quick health management decision, including for confiscated slow loris (Nycticebus spp.). The confiscated slow loris should be rehabilitated in a rehabilitation center before being released. It is essential to monitor the welfare of slow loris to ensure that candidates are released. Assessment of animal welfare status requires representative measurable criteria and indicators. However, there is no standardized BCS for slow loris yet. This study focuses on developing and validating BCS based on body weight and circumference. In this study, 180 individuals were evaluated and scored. We measured body weight and circumferences to validate the assessment of BCS. There are no significant differences in body weight and circumferences within species and sexes. Muscle mass and fat deposits were palpated, visually viewed, and grouped in five BCS. There was a significant difference in body weight and circumference between BCS levels. According to this study, the development of BCS is valid and can be used to slow loris in prevailing circumstances and any ex-situ facilities.

Spontaneous expression of the gene of KI67 and P53 in cynomolgus monkeys infected with papillomavirus.

Background and Aim: Cynomolgus monkeys (Macaca fascicularis) develop spontaneous infection of Papillomavirus (PV); thus, potentially beneficial for modeling human PV (HPV) infection study. Contrary to human origin, infection in cynomolgus monkeys does not always show evident clinical symptoms of cervical cancer. The absence of cervical cancer clinical symptoms leads us to investigate the molecular mechanism of the HPV infection in cynomolgus monkeys. This study aimed to investigate the messenger ribonucleic acid (mRNA) expression levels of KI67 and P53 genes, majorly known as biomarker oncogenesis of PV infection. Materials and Methods: The polymerase chain reaction (PCR) technique was used with MY11/MY09 primer to screen PV in cynomolgus monkey, further grouped as positive-PV and negative-PV infection groups. Real-time quantitative PCR was also applied to quantify the mRNA expression levels of KI67 and P53 genes in animals. Results: Increased expression of mRNA level of KI67 genes was significantly higher in Positive- PV group than negative-PV group. In contrast, the P53 mRNA expression level increased markedly higher in the negative-PV group than in the positive-PV group. Conclusion: Our study describes the potential of cynomolgus monkeys as a spontaneous oncogenesis model of PV infection-type. However, we used a limited number of cancer genetic markers. So, further study of other genetic markers is required to prove that cervical cancer could be developed naturally in cynomolgus monkeys.

Increased expression of GAPDH in cynomolgus monkeys with spontaneous cognitive decline and amyloidopathy reminiscent of an Alzheimer's-type disease is reflected in the circulation.

Previous studies of aging cynomolgus monkeys from our group identified spontaneous age-associated cognitive declines associated with biomarkers and brain lesions reminiscent of Alzheimer's Disease (AD), in a proportion of aged monkeys. However, the molecular mechanisms that underlie the spontaneous amyloid disorders and cognitive declines observed in these affected monkeys have yet to be investigated in detail. Using reverse transcriptase quantitative real time PCR techniques, normalized to the ACTB housekeeping gene, we analyzed the expression patterns of a number of genes which have been implicated in amyloid and tau abnormalities, in well-characterized aged cynomolgus monkeys with cognitive decline. A significantly increased expression of the genes coding for glyceraldehyde 3-phosphate dehydrogenase (GAPDH), was found in aged-cognitive decline monkeys compared to age-matched healthy controls. GAPDH has been implicated in several neurodegenerative diseases and interacts with beta amyloid precursor proteins. These findings provide support for the utilization of cynomolgus macaques in translational preclinical research as valid spontaneous models in experimental investigations of the relationships among aging, cognitive decline, and the neuropathy of AD.

Exposure of Wild Sumatran Tiger (Panthera tigris sumatrae) to Canine Distemper Virus.

Canine distemper virus (CDV) is recognized as a conservation threat to Amur tigers (Panthera tigris altaica) in Russia, but the risk to other subspecies remains unknown. We detected CDV neutralizing antibodies in nine of 21 wild-caught Sumatran tigers (42.9%), including one sampled on the day of capture, confirming exposure in the wild.

Granulovacuolar Degeneration in Brains of Senile Cynomolgus Monkeys.

Neurons with histopathological changes consistent with granulovacuolar degeneration (GVD) were found in brain sections from aged cynomolgus monkeys (Macaca fascicularis) with clinical and pathological signs of cognitive aging. To our knowledge, this is the first reported description of GVD in non-human primates. GVD-like lesions were found also in age-matched cognitively healthy subjects, albeit in lower numbers, suggesting that they may relate to aging and the increase may have tendency to increase with the memory deficits. The increased incidence of GVD-like lesions in memory-impaired subjects with pahological backgrounds of senile plaques (SPs) and tauopathy is, however, an interesting observation of relevance to the characterization of pathologies in the spontaneous cynomolgus monkey model of human Alzheimer's type of brain pathology.

The success rate in a complicated spatial memory test is determined by age, sex, life history and search strategies in cynomolgus monkeys.

In a retrospective analysis of data from three studies using a delayed response task in cynomolgus monkeys, we examined the subjects' search patterns and success rates. Twenty-seven monkeys of both sexes, divided into three age groups, were tasked with retrieving two food items hidden in an array of six identical opaque cups. Although the task was challenging for all subjects, generating a high level of guesswork, evidence of common behaviors when approaching the spatial memory test were found. The search patterns employed by the monkeys suggest the use of landmark cues, adaption in response to failure and chronological memory recall. These strategies appeared to be shared by most subjects, however, the overall success rate appeared to also depend on individual characteristics including age, gender and whether the subject had been born in caged captivity or not. By elucidating some of the underlying cognitive mechanisms, these findings may serve to refine interpretation of future studies using similar delayed response tasks in non-human primates.

Poor memory performance in aged cynomolgus monkeys with hippocampal atrophy, depletion of amyloid beta 1-42 and accumulation of tau proteins in cerebrospinal fluid.

BACKGROUND: Due to their similarities in behavior and disease pathology to humans, non-human primate models are desirable to complement small animals as models for the study of age-related dementia. MATERIALS AND METHODS: Based on their performance on delayed response task (DRT) tests of memory, aged cynomolgus monkeys were divided into two groups to compare high-performing (n=6) and low-performing (n=6) subjects. Both groups were tested for biomarkers related to Alzheimer's disease and their brains were scanned using structural magnetic resonance imaging. RESULTS: The subjects with poor DRT performance had evidence of atrophy in the hippocampus and cortical areas, significantly lower cerebrospinal fluid levels of amyloid beta amino acid 1-42 (p<0.001) and higher cerebrospinal fluid total tau levels (p<0.05) compared to the group performing well on the DRT tests. CONCLUSION: Old, memory-impaired Cynomolgus monkeys may be useful as a spontaneous non-human primate model for investigations of age-related neurodegenerative diseases.

Mice do not habituate to metabolism cage housing--a three week study of male BALB/c mice.

The metabolism cage is a barren, non-enriched, environment, combining a number of recognized environmental stressors. We investigated the ability of male BALB/c mice to acclimatize to this form of housing. For three weeks markers of acute and oxidative stress, as well as clinical signs of abnormality were monitored. Forced swim tests were conducted to determine whether the animals experienced behavioral despair and the serotonergic integrity was tested using an 8-OH-DPAT challenge. The metabolism cage housed mice excreted approximately tenfold higher amounts of corticosterone metabolites in feces throughout the study when compared to controls. Urinary biomarkers confirmed that these mice suffered from elevated levels of oxidative stress, and increased creatinine excretions indicated increased muscle catabolism. Changes in the core body temperature (stress-induced hyperthermia) and the fur state of the mice also indicated impaired well-being in the metabolism cage housed mice. However, monitoring body weight and feed intake was found misleading in assessing the wellbeing of mice over a longer time course, and the forced swim test was found poorly suited for studying chronic stress in mice in the present setup. In conclusion, the mice were found not to acclimatize to the metabolism cages whereby concern for animal welfare would dictate that mice should be housed in this way for as short periods as possible. The elevated degree of HPA axis activity, oxidative stress, and increased overall metabolism warrant caution when interpreting data obtained from metabolism cage housed mice, as their condition cannot be considered representative of a normal physiology.