Introduction : brain science : inside out

BRAIN – remains as the most sophisticated organ in the known universe. While more has been learned about it in the past two hundred years, we are still at a very early stage in our understanding. The field of Neuroscience is still in its infancy, but is rapidly exploding – turning many yesterday’s brain “myth” to today’s brain “facts”

smART Brain

In the smART Brain section, visitors can expect a dynamic yet entertaining science journey and educational time. “The Master Hat” is specially designed to portray the left-right brain dominance : the right brain is often regarded as the more creative side whilst the left brain is regarded as the analytical side

Expression profiling of genes involved in the development and function of skeletal muscles in Ts1Cje mouse model of down syndrome

Introduction: Down syndrome (DS) is caused by trisomy of human chromosome 21 (HSA21). Motor dysfunction due to hypotonia has limited labour productivity and have significant effects on socio-economic status in DS individuals. Ts1Cje, a mouse model of DS that exhibits muscle weakness was employed, to investigate the expression profile of selected trisomic and disomic genes involved in skeletal muscle structure and function. Methods: Quadriceps and triceps were harvested from the Ts1Cje (C57BL/6) postnatal day 60-70 mice and corresponding wild-type littermates. Total RNA extracted from these tissues was subjected for quantitative expression profiling of three trisomic genes (Itsn1, Synj1 and Rcan1) involved in neurotransmission and six disomic genes (Lamc1, Leprel1, Myl6b, Msn, Pgm5 and Tmod1) essential for maintenance of muscle structure and function. Real-time quantitative PCR method was used for the profiling. Results: Differential gene expression in DS is reflected by 1.5-fold or more increase in the level of expression as predicted by the gene dosage imbalance hypothesis. The analysis showed no significant changes in the expression level of trisomic genes (Itsn1, Synj1 and Rcan1). On contrary, disomic genes, Leprel1 and Pgm5, were upregulated for more than 1.5-fold in DS quadriceps whereas Lamc1, Myl6b and Pgm5 were upregulated for more than 1.5 fold in DS triceps as compared to the wild-type group. Conclusions: Our findings suggest that the dysregulation of Lamc1, Leprel1, Myl6b and Pgm5 genes is associated to muscle weakness seen in Ts1Cje and may play a role in molecular pathogenesis of muscle weakness in DS

The resin-embedded cornea prepared via rapid processing protocol : a good histomorphometric target for clinical investigation in opthalmology and optometry.

This study illustrates and quantifies the changes on corneal tissue between the paraffin-embedded and resin-embedded blocks and thus, selects a better target in investigational ophthalmology and optometry via light microscopy. Corneas of two cynomolgus monkeys (Macaca fascicularis) were used in this study. The formalin-fixed cornea was prepared in paraffin block via the conventional tissue processing protocol (4-day protocol) and stained with haematoxylin and eosin. The glutaraldehyde-fixed cornea was prepared in resin block via the rapid and modified tissue processing procedure (1.2-day protocol) and stained with toluidine blue. The paraffin-embedded sample exhibits various undesired tissue damage and artifact such as thinner epithelium (due to the substantial volumic extraction from the tissue), thicker stroma layer (due to the separation of lamellae and the presence of voids) and the distorted endothelium. In contrast, the resin-embedded corneal tissue has demonstrated satisfactory corneal ultrastructural preservation. The rapid and modified tissue processing method for preparing the resin-embedded is particularly beneficial to accelerate the microscopic evaluation in ophthalmology and optometry

Challenges and future perspectives for 3D cerebral organoids as a model for complex brain disorders

The human brain is made up of billions of neurons and glial cells which are interconnected and organized into specific patterns of neural circuitry, and hence is arguably the most sophisticated organ in human, both structurally and functionally. Studying the underlying mechanisms responsible for neurological or neurodegenerative disorders and the developmental basis of complex brain diseases such as autism, schizophrenia, bipolar disorder, Alzheimer’s and Parkinson’s disease has proven challenging due to practical and ethical limitations on experiments with human material and the limitations of existing biological/animal models. Recently, cerebral organoids have been proposed as a promising and revolutionary model for understanding complex brain disorders and preclinical drug screening

Acute oral toxicity and biodistribution study of zinc aluminium-levodopa nanocomposite

Layered double hydroxide (LDH) is an inorganic-organic nano-layered material that harbours drug between its two-layered sheets, forming a sandwich-like structure. It is attracting a great deal of attention as an alternative drug delivery (nanodelivery) system in the field of pharmacology due to their relative low toxic potential. The production of these nanodelivery systems, aimed at improving human health through decrease toxicity, targeted delivery of the active compound to areas of interest with sustained release ability. In this study, we administered zinc-aluminium-LDH-levodopa nanocomposite (ZAL) and zinc-aluminium nanocomposite (ZA) to Sprague Dawley rats to evaluate for acute oral toxicity following OECD guidelines. The oral administration of ZAL and ZA at a limit dose of 2,000 mg/kg produced neither mortality nor acute toxic signs throughout 14 days of the observation. The percentage of body weight gain of the animals showed no significant difference between control and treatment groups. Animal from the two treated groups gained weight continuously over the study period, which was shown to be significantly higher than the weight at the beginning of the study (P < 0.05). Biochemical analysis of animal serum showed no significant difference between rats treated with ZAL, ZA and controls. There was no gross lesion or histopathological changes observed in vital organs of the rats. The results suggested that ZAL and ZA at 2,000 mg/kg body weight in rats do not induce acute toxicity in the animals. Elemental analysis of tissues of treated animals demonstrated the wider distribution of the nanocomposite including the brain. In summary, findings of acute toxicity tests in this study suggest that zinc-aluminium nanocomposite intercalated with and the un-intercalated were safe when administered orally in animal models for short periods of time. It also highlighted the potential distribution ability of Tween-80 coated nanocomposite after oral administration

Histomorphometric profile of the corneal response to short-term reverse-geometry orthokeratology lens wear in primate corneas: a pilot study

Purpose: To investigate the histological changes in primate cornea induced by short-term overnight orthokeratology (OK). Methods: Nine young adult primates were used. One animal served as negative control. The remaining 8 animals wore reverse-geometry OK lenses for periods of 4, 8, 16, and 24 hours on 1 eye with the other eye as control. Central and midperipheral corneal thickness, as well as ultrastructural changes in corneal epithelium, stroma and endothelium in response to OK lenses, were evaluated. Results: OK significantly reduced the thickness of the central cornea in all treatment groups. The central corneal thinning was both stromal and epithelial in origin. Substantial midperipheral corneal thickening was seen in 16-hour and 24-hour lens-wear groups and this effect was both stromal and epithelial in origin as well. Histology evidence indicated the primary epithelial response in the central cornea was compression of cells that resulted in wing cells becoming shorter and basal cells being squatted rather than lost or migration of cell layers. These pronounced cell shape changes occurred without compromising the structural integrity of the desmosomes. The thickened corneal epithelium has normal cell layers. The squamous cells have larger surface sizes and are composed of oval instead of flattened nuclei. This implied delayed surface cell exfoliation at the thickened midperipheral epithelium. Physical presence of OK lens over the cornea did not influence the microstructures of microvilli and microplicae, endothelium, and collagen distribution. Conclusions: The primate cornea, particularly the corneal epithelium, responds rapidly to the application of reverse-geometry OK lenses with significant epithelial cell shape alterations with short-term OK lens wear. This finding suggests that the corneal epithelium is moldable in response to the physical forces generated by the OK lenses

Spatiotemporal expression profiling and molecular characterisation of miR-344b and miR-344c in the developing mouse brain

MicroRNAs are small non-coding RNAs of about 22 nucleotides that regulate gene expression through inhibition or repression processes during post-transcriptional or translational stages. Studies have shown that miRNAs play a crucial role in spatiotemporal regulation of the brain development. A recent study had shown that miR-344 is expressed in a developing mouse brain. In this study, we focused to characterise the spatiotemporal expression of miR-344b and miR-344c during the development of mouse brain. Out in situ hybridisation studies have shown that both miR-344b and miR-344c were strongly expressed in the germinal layer during the early stages of mouse brain development. Postnatally, expression of miR-344b was not detectable in P1 and adult brains. In contrast, miR-344c was expressed globally in P1 brain and was expressed exclusively in the olfactory bulb and granular cell layer of the cerebellum in the adult mouse brain. A subsequent stemloop RT-qPCR analysis showed that expression of the miR-344b and miR-344c was increased from E11.5 and peaked at E15.5. Postnatally, expression level of the miR-344b was reduced while miR-344c continued to express until adulthood. We further investigated the expression of miR-344b and miR-344c in adult mouse multiple organs and the pancreas showed the highest expression for both miRNAs. Subsequent bioinformatics analysis predicted that miR-344b and miR-344c were found to target a total of 1540 and 863 downstream target genes respectively. Genes associated with transcription regulation and nervous system development were subjected to further screening. We found that Olig2 and Otx2 were predicted as the potential downstream target gene for miR-344b and miR-344c respectively. However, luciferase protein suppression assay showed that the expression of Olig2 and Otx2 were not suppressed by overexpression of miR-344b and miR-344c. In conclusion, miR-344b and miR-344c were expressed in the developing mouse brain and may play a role during early mouse brain development although not directly targeting Olig2 and Otx2

Discovery of anatomic variant of saphenous nerve from human cadaver dissection

Introduction: Saphenous nerve is the longest and largest pure sensory nerve, supplying the medial side of the thigh, leg and foot. Materials and Methods: In the present case study, during routine cadaveric dissection of the antero-medial part of the thigh, an interesting anomalous pattern of saphenous nerve was seen in the right lower limb of a 62 years old embalmed male cadaver from the Department of Human Anatomy, Universiti Putra Malaysia (UPM). Results: This saphenous nerve can be recognised as an unusual anatomical variant in which it gives a motor branch to the sartorius muscle during traversing the adductor canal and it was accompanied by blood vessels at the same time. The nerve continues its usual course and pierces the fascia lata, between the tendon of sartorius and gracilis and becomes subcutaneous. Conclusion: Knowledge of the variant anatomy of the saphenous nerve is important to surgeon in avoiding nerve injuries during adductor canal nerve block, nerve entrapment surgery, reconstructive surgery, pain management services and knee surgery successfully

In silico analysis of mRNA:miR-3099 interaction

Introduction: MicroRNAs (miRNA) are small non-coding RNAs and have crucial role in gene expression and protein synthesis regulation, especially in nervous system and brain development. A novel miR-3099 was found highly express throughout embryogenesis especially in the developing central nervous system. Moreover, miR-3099 was also expressed upon neuronal differentiation in in vitro system suggesting that miR-3099 is a potential regulator during neuronal development. Therefore, objective of this study is to predict target genes of miR-3099 via in-silico analysis. These analyses will predict potential downstream targets for miR-3099 and their relationship to signalling pathways with special focus on neuronal function and brain development. Methods: Four different prediction software, miRDB, miRanda, TargetScan and DIANA micro-T, were employed to identify the candidate target genes of miR-3099. The predicted downstream targeted genes were selected based on the database criteria, prior to BioVenn clustering to identify the common targeted genes. The targeted genes that were predicted by at least three different databases were subjected to DAVID bioinformatics analysis to understand the biological process and function of these targeted genes. Results: Based on the analysis, a total of 1676 predicted genes were targeted by miR-3099. Of these, 73 genes were predicted by three software and 22 genes were predicted by all the four software. Majority of the targeted genes were annotated as involved in positive regulation of transcription activity and were identified as related to neuronal and brain development. Hence, the predicted downstream targets of miR-3099 warrant further investigation to validate the in silico analysis