Kiranmai S. Rai

Enhanced production and dendritic growth of new dentate granule cells in the middle-aged hippocampus following intracerebroventricular FGF-2 infusions

Declined production and diminished dendritic growth of new dentate granule cells in the middle‐aged and aged hippocampus are correlated with diminished concentration of fibroblast growth factor‐2 (FGF‐2). This study examined whether increased FGF‐2 concentration in the milieu boosts both production and dendritic growth of new dentate granule cells in the middle‐aged hippocampus. The FGF‐2 or vehicle was infused into the posterior lateral ventricle of middle‐aged Fischer (F)344 rats for 2 weeks using osmotic minipumps. New cells born during the first 12 days of infusions were labeled via daily intraperitoneal injections of 5′‐bromodeoxyuridine (BrdU) and analysed at 10 days after the last BrdU injection. Measurement of BrdU+ cells revealed a considerably enhanced number of new cells in the subgranular zone (SGZ) and granule cell layer (GCL) of the dentate gyrus (DG) ipsilateral to FGF‐2 infusions. Characterization of β‐III tubulin+ neurons among newly born cells suggested an increased addition of new neurons to the SGZ/GCL ipsilateral to FGF‐2 infusions. Quantification of DG neurogenesis at 8 days post‐infusions via doublecortin (DCX) immunostaining also revealed the presence of an enhanced DG neurogenesis ipsilateral to FGF‐2 infusions. Furthermore, DCX+ neurons in FGF‐2‐infused rats exhibited enhanced dendritic growth compared with their counterparts in vehicle‐infused rats. Thus, subchronic infusion of FGF‐2 is efficacious for stimulating an enhanced DG neurogenesis from neural stem/progenitor cells in the middle‐aged hippocampus. As dentate neurogenesis is important for hippocampal‐dependent learning and memory and DG long‐term potentiation, strategies that maintain increased FGF‐2 concentration during ageing may be beneficial for thwarting some of the age‐related cognitive impairments.

Efficacy of Rajayoga meditation on positive thinking: An index for self-satisfaction and happiness in life

OBJECTIVES Psychological studies have shown that brief period of mindfulness meditation significantly improves critical cognitive skills. But, there are no studies which have assessed the effects of Brahma Kumaris Rajayoga Meditation (BKRM) practice on positive thinking and happiness in life. The present study was designed to test the hypothesis is BKRM enhances positive thinking and that essential to attain higher levels of self-satisfaction and happiness in life. MATERIAL AND METHODS This study is a cross sectional comparative study which was done between Rajayoga meditators and non-meditators. This study was conducted at BKRM Centres at Manipal and Udupi in Karnataka, India. Fifty subjects were selected for this study, which included those practising BKRM in their normal routine life (n=25) and non-meditators (n=25) who were aged 42.95+/15.29 years. Self-reported Oxford happiness questionnaire (OHQ) was administered to all subjects and their happiness scores and status were assessed and compared. Items related to self-satisfaction in life were selected from the OHQ and compared between meditators and non-meditators. Participants completed self-reported OHQ, from which data of happiness status and self-satisfaction in relation to meditation duration and frequency were analyzed by descriptive statistics and test of hypothesis. RESULTS Mean happiness scores of BKRM were significantly higher (p<0.001) in meditators as compared to those in non-meditators. The number of meditators experiencing happiness status were significantly higher (p<0.05) in comparison with non-meditators. Additionally, meditators scored significantly higher on self-satisfaction items (p<0.001) as compared to non-meditators. There was no correlation between age and years of meditation practice with happiness score and self-satisfaction score. CONCLUSION BKRM helps in significantly increasing self-satisfaction and happiness in life by enhancing positive thinking. Irrespective of age and years of short-term or long-term meditation practice, enhanced positive thinking increases self-satisfaction and happiness in life.Objectives: Psychological studies have shown that brief period of mindfulness meditation significantly improves critical cognitive skills. But, there are no studies which have assessed the effects of Brahma Kumaris Rajayoga Meditation (BKRM) practice on positive thinking and happiness in life. The present study was designed to test the hypothesis is BKRM enhances positive thinking and that essential to attain higher levels of self-satisfaction and happiness in life. Material and Methods: This study is a cross sectional comparative study which was done between Rajayoga meditators and non-meditators. This study was conducted at BKRM Centres at Manipal and Udupi in Karnataka, India. Fifty subjects were selected for this study, which included those practising BKRM in their normal routine life (n=25) and non-meditators (n=25) who were aged 42.95+/15.29 years. Self-reported Oxford happiness questionnaire (OHQ) was administered to all subjects and their happiness scores and status were assessed and compared. Items related to self-satisfaction in life were selected from the OHQ and compared between meditators and non-meditators. Participants completed self-reported OHQ, from which data of happiness status and self-satisfaction in relation to meditation duration and frequency were analyzed by descriptive statistics and test of hypothesis. Results: Mean happiness scores of BKRM were significantly higher (p<0.001) in meditators as compared to those in non-meditators. The number of meditators experiencing happiness status were significantly higher (p<0.05) in comparison with non-meditators. Additionally, meditators scored significantly higher on self-satisfaction items (p<0.001) as compared to non-meditators. There was no correlation between age and years of meditation practice with happiness score and self-satisfaction score. Conclusion: BKRM helps in significantly increasing self-satisfaction and happiness in life by enhancing positive thinking. Irrespective of age and years of short-term or long-term meditation practice, enhanced positive thinking increases self-satisfaction and happiness in life.

Combined Supplementation of Choline and Docosahexaenoic Acid during Pregnancy Enhances Neurodevelopment of Fetal Hippocampus

Choline is an essential nutrient for humans which plays an important role in structural integrity and signaling functions. Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid, highly enriched in cell membranes of the brain. Dietary intake of choline or DHA alone by pregnant mothers directly affects fetal brain development and function. But no studies show the efficacy of combined supplementation of choline and DHA on fetal neurodevelopment. The aim of the present study was to analyze fetal neurodevelopment on combined supplementation of pregnant dams with choline and DHA. Pregnant dams were divided into five groups: normal control [NC], saline control [SC], choline [C], DHA, and C + DHA. Saline, choline, and DHA were given as supplements to appropriate groups of dams. NC dams were undisturbed during entire gestation. On postnatal day (PND) 40, brains were processed for Cresyl staining. Pups from choline or DHA supplemented group showed significant (p < 0.05) increase in number of neurons in hippocampus when compared to the same in NC and SC groups. Moreover, pups from C + DHA supplemented group showed significantly higher number of neurons (p < 0.001) in hippocampus when compared to the same in NC and SC groups. Thus combined supplementation of choline and DHA during normal pregnancy enhances fetal hippocampal neurodevelopment better than supplementation of choline or DHA alone.

Dosage and Passage Dependent Neuroprotective Effects of Exosomes Derived from Rat Bone Marrow Mesenchymal Stem Cells: An In Vitro Analysis

BACKGROUND Neurodegenerative diseases comprise a group of disorders for which no treatment is available till date. Stem cell based therapy offers great hope and promise. However, stem cell transplantation is associated with certain disadvantages like poor targeted migration, engraftment and survival of the transplanted cells. MATERIAL & METHOD Exosomes, a type of extracellular membrane vesicle released by all cell types including stem cells, offer an alternative to stem cell transplantation. Exosome carry a wide array of biomolecules and are implicated in exhibiting substantial benefits in the repair/regeneration of the injured tissue. Thus, exosomes offer an alternative therapeutic approach as a substitute of cell transplantation. In order to utilize exosomes for therapeutic purpose, it is essential to evaluate the appropriate passage number and the dosage to avoid possible cytotoxic effects. Here, we isolated exosomes from different passages of rat bone marrow mesenchymal stem cells (BM-MSC) and analysed the neuroprotective potential of BM-MSC exosomes in an in vitro model of excitotoxicity. RESULT Our results demonstrated that the exosomes isolated from early passage of rat BM-MSC exhibited more efficient neuroprotective potential as opposed to later passages derived exosomes. Furthermore, the neuroprotective efficacy of exosome is dosage dependent. i.e. the lower dosage of exosomes was found to be neuroprotective, whereas higher dosage of exosomes (from later passages) was found to be detrimental to neurons. The early passage derived exosomes protected neurons through anti-apoptotic, anti-necrotic and anti-oxidant mechanisms. CONCLUSION Our study suggests that adult stem cells derived exosomes could be a potential therapeutic agent to confer neuroprotection in neurodegenerative diseases like Alzheimers disease.

Impact of seasonal variant temperatures and laboratory room ambient temperature on mortality of rats with ischemic brain injury

INTRODUCTION A popular rat model for hypoperfusion ischemic brain injury is bilateral common carotid artery occlusion (BCCAO). BCCAO surgery when performed in varying geographical locations and during different seasons of the year is reported to have variable mortality rates. Studies have also documented the diminishing influence of Ketamine-Xylazine (KT-XY) on thermoregulatory functions in rodents. AIM To explore the impact of seasonal variant temperatures and laboratory room ambient temperatures on mortality of rats following BCCAO surgery. MATERIALS AND METHODS The study has two parts: 1 The first part is an analysis of a three year retrospective data to explore the association between the geographical season (hot summer and cold winter) induced laboratory room ambient temperature variations and the mortality rate in KT-XY anaesthetized BCCAO rats. 2. The second part investigated the effect of conditioned laboratory room ambient temperature (CAT) (23-25(0)C) in KT-XY anaesthetized BCCAO group of rats. Rats were divided into 4 groups(n =8/group) as-Normal control, BCCAO and Sham BCCAO where they were all exposed to unconditioned ambient temperature (UCAT) during their surgery and postoperative care. And finally fourth group rats exposed to CAT during the BCCAO surgery and postoperative care. RESULTS Pearsons chi-square test indicates a significantly high association (p<0.006) between post-BCCAO mortality and hot season of the year. CAT during the hot season reduced the mortality rate (24% less) in post- BCCAO rats compared to the rats of UCAT. CONCLUSION Despite seasonal variations in temperature, conditioning the laboratory room ambient temperatures to 23-25(0)C, induces hypothermia in KT-XY anaesthetized ischemic brain injured rodents and improves their survival rate.

Infusion of human embryonic kidney cell line conditioned medium reverses kainic acid induced hippocampal damage in mice.

BACKGROUND AIMS Hippocampal neurodegeneration is one of the hallmarks in neurological and neurodegenerative diseases such as temporal lobe epilepsy and Alzheimer disease. Human embryonic kidney (HEK) cells are a mixed population of cells, including neurons, and their conditioned medium is enriched with erythropoietin (EPO). Because EPO is a known neuroprotectant, we hypothesized that infusion of HEK cells or HEK-conditioned medium (HEK-CM) may provide neuroprotection against kainic acid (KA)-induced hippocampal damage in mice. METHODS Adult CF1 mice were treated with KA to induce hippocampal damage. On 3rd and 5th days after KA treatment, HEK cells or HEK-CM was infused intravenously through the tail vein. On the 7th and 8th days after KA treatment, all groups of mice were subjected to cognitive and depression assessment by use of a novel object recognition test and a forced swim test, respectively. Subsequent to this assessment, mice were killed and the brain samples were used to assess the histopathology and messenger RNA expression for EPO and B-cell lymphoma-2 (Bcl-2). RESULTS We found that infusion of HEK cells/HEK-CM improves cognitive function and alleviates symptoms of depression. Histological assessment demonstrates complete neuroprotection against KA-mediated excitotoxicity, and the hippocampal cytoarchitecture of HEK cells/HEK-CM treated mice was comparable to normal control mice. HEK cells/HEK-CM treatment could provide neuroprotection by upregulating the endogenous EPO and Bcl-2 in KA-treated mice. CONCLUSIONS Our present data demonstrate for the first time that infusion of HEK cells/HEK-CM can prevent excitotoxic hippocampal damage and alleviate consequent behavioral abnormalities.

Modified directed self-learning sessions in physiology with prereading assignments and Pecha Kucha talks: perceptions of students

The present study reports perceptions of first-year undergraduate medical students ( n = 120), regarding modified directed self-learning (DSL) sessions in physiology. Students were provided with prereading assignments (faculty developed PowerPoint slides containing diagrams with incomplete labeling/flowcharts with missing steps) pertaining to the DSL topic 1 wk before the scheduled small-group DSL presentations. During DSL presentation sessions, which were facilitated by teachers, a few students individually presented learning objectives in the specified topic. Apart from that, students discussed answers for the questions in the prereading assignment. Students were also given an opportunity to use technology to support DSL, by way of involving them in Pecha Kucha (PK) talks. The impact of the modified DSL method was determined by requesting students to respond to a validated questionnaire. Frequency analysis of the responses revealed that >60% of students were positive about the modified DSL sessions improving their DSL, presentation, collaborative learning, and information retrieving skills. Students agreed that PK talks helped them to learn how to organize content (65%), present concise information (65.8%), and apply creativity (72.5%). Even though small in number, there were comments that the prereading assignments were useful for learning. The present study revealed that, even though students actively participated in modified DSL sessions, their perceptions on satisfaction and usefulness of the same toward achievement of various skills were not encouraging. The study generated significant results, which implies that undergraduate medical students should be oriented on the relevance of active learning strategies in their future studies.