As a human replacement, the crab-eating macaque (Macaca fascicularis) is an invaluable non-human primate model for biomedical research, but the lack of genetic information on this primate has represented a significant obstacle for its broader use.

The accumulation and aggregation of misfolded proteins in the brain, such as amyloid-β (Aβ) and hyperphosphorylated tau, is a neuropathological hallmark of Alzheimer’s disease (AD). Previously, we developed and validated a novel non-human primate model for sporadic AD (sAD) research using intracerebroventricular administration of streptozotocin (icv STZ). To date, no characterization of AD-related genes in different brain regions has been performed. Therefore, in the current study, the expression of seven amyloid precursor protein (APP) pathway-related and five tau phosphorylation-related genes was investigated by quantitative real-time PCR experiments, using two matched-pair brain samples from control and icv STZ-treated cynomolgus monkeys. The genes showed similar expression patterns within the control and icv STZ-treated groups; however, marked differences in gene expression patterns were observed between the control and icv STZ-treated groups. Remarkably, other than β-secretase (BACE1) and cyclin-dependent kinase 5 (CDK5), all the genes tested showed similar expression patterns in AD models compared to controls, with increased levels in the precuneus and occipital cortex. However, significant changes in gene expression patterns were not detected in the frontal cortex, hippocampus, or posterior cingulate. Based on these results, we conclude that APP may be cleaved via the general metabolic mechanisms of increased α- and γ-secretase levels, and that hyperphosphorylation of tau could be mediated by elevated levels of tau protein kinase, specifically in the precuneus and occipital cortex.

Background: Obesity due to an excessive intake of nutrient disturbs the hypothalamus-mediated energy metabolism subsequently develops metabolic disorders. In this study, we investigated the effect of pine needle extract (PNE) on the hypothalamic proopiomelanocortin (POMC) neurons involved in the regulation of energy balance via melanocortin system and fat tissue metabolism. Methods: We performed electrophysiological and immunohistochemical analyses to determine the effect of PNE on POMC neurons. Mice were fed a normal or high-fat diet for 12 weeks, then received PNE for the last 2 weeks to measure the following physiological indices: Body weight, food intake, fat/lean mass, glucose metabolism, and plasma leptin levels. In addition, changes of thermogenic, lipolytic, and lipogenetic markers were evaluated in brown adipose tissue (BAT) and white adipose tissue (WAT) by western blotting, respectively. Results: PNE increased hypothalamic POMC neuronal activity, and the effect was abolished by blockade of melanocortin 3/4 receptors (MC3/4Rs). PNE decreased body weight, fat mass, plasma leptin levels, and improved glucose metabolism after high-fat-induced obesity. However, PNE did not change the expression of thermogenic markers of the BAT in HFD fed groups, but decreased only the lipogenetic markers of WAT. This study suggests that PNE has a potent anti-obesity effect, inhibiting lipogenesis in WAT, even though HFD-induced leptin resistance-mediated disruption of POMC neuronal activity.

Transposable element (TE) has the ability to insert into certain parts of the genome, and due to this event, it is possible for TEs to generate new factors and one of these factors are microRNAs (miRNA). miRNAs are non-coding RNAs made up of 19 to 24 nucleotides and numerous miRNAs are derived from TE. In this study, to support general knowledge on TE and miRNAs derived from TE, several bioinformatics tools and databases were used to analyze miRNAs derived from TE in two aspects: evolution and human disease. The distribution of TEs in diverse species presents that almost half of the genome is covered with TE in mammalians and less than a half in other vertebrates and invertebrates. Based on selected evolution-related miRNAs studies, a total of 51 miRNAs derived from TE were found and analyzed. For the human disease-related miRNAs, total of 34 miRNAs derived from TE were organized from the previous studies. In summary, abundant miRNAs derived from TE are found, however, the function of miRNAs derived from TE is not informed either. Therefore, this study provides theoretical understanding of miRNAs derived from TE by using various bioinformatics tools.

Tyrosinase is a copper-containing enzyme that regulates melanin biosynthesis and is encoded by the tyrosinase (TYR) gene. Previous studies demonstrated that mutations in TYR could lead to oculocutaneous albinism type 1 (OCA1) owing to the failure of melanin formation. Although a previous study found that albinism in the rhesus monkey was derived from a mutation in TYR, the identification and characterization of this gene in non-human primates has not been achieved thus far. Thus, using the rapid amplification of cDNA ends (RACE) and internal reverse transcription PCR (RT-PCR) we identified the full-length sequence of TYR in the crab-eating macaque, and two different transcript variants (TYR_1 and TYR_2). While TYR_1 comprised five exons and its coding sequence was highly similar to that of humans, TYR_2 comprised four exons and was generated by a third-exon-skipping event. Interestingly, these two transcripts were also present in the African green monkey (Old World monkey) and the common marmoset (New World monkey). Deduced amino acid sequence analyses revealed that TYR_2 had a shorter C-terminal region than TYR_1 owing to the exon-skipping event. Thus, the present study is the first to identify and characterize a full-length TYR gene in a non-human primate, while the further validation of the third-exon-skipping in TYR indicates that this event is well conserved in the primate lineage. Therefore, this study provides useful and important information for the study of albinism using non-human primate models.

Sang-Je Park, Young-Hyun Kim, Sang-Rae Lee, Se-Hee Choe, Myung-Jin Kim, Sun-Uk Kim, Ji-Su Kim, Bo-Woong Sim, Bong-Seok Song, Kang-Jin Jeong, Yeung-Bae Jin, Youngjeon Lee, Young-Ho Park, Young Il Park, Jae-Won Huh, and Kyu-Tae Chang. Mol. Cells 2015;38:950-8. https://doi.org/10.14348/molcells.2015.0121