Publications by authors named "Bommana Raghunath Reddy"

4 Publications

  • Page 1 of 1

Proteome profile of telencephalon associates attenuated neurogenesis with chronic stress induced mood disorder phenotypes in zebrafish model.

Pharmacol Biochem Behav 2021 May 5;204:173170. Epub 2021 Mar 5.

Applied Biology, CSIR-Indian Institute of Chemical Technology (IICT), Tarnaka, Uppal Road, Hyderabad 500007, India; Academy of Scientific and Industrial Research, Ghaziabad 201002, India. Electronic address:

Debilitating mental illness like depression and related mood disorders is due to the disruption in circuitry that controls emotion, motivation, and reward, characterized by disparate phenotypes like decrease in socialization, motivation, threshold for threat apprehension, etc. Chronic stress is a major factor in the etiology of these disorders. Here, using a chronic unpredictable stress (CUS) paradigm the characterization of an array of mood disorder phenotypes in adult zebrafish, in comparison to normal control unstressed fish, was achieved using a battery of behavioral assays including novel ones comprising social interaction test, feed approach test, threat response test and novel tank test. For the predictive validity of the model for mood disorders, the mitigative role of a slow (imipramine) and fast (ketamine) acting antidepressant was assessed. The molecular changes associated with CUS-induced mood disorder phenotype was investigated utilizing a high throughput method called isobaric tag for relative and absolute quantification (iTRAQ) in telencephalon, the region critically associated with the processing of emotional information in the fish brain. Out of 222 proteins identified to be significantly altered, 58 were differentially expressed across the stress and antidepressant-treatment groups at more than one fold (in log2) change. Of these proteins, some were implicated in earlier studies on mood disorders such as CABP1, PER2, mTOR, etc. The enrichment of altered proteins by Ingenuity Pathway Analysis (IPA) led us to mTOR and opioid signaling pathways, the top canonical pathways affected in the fish telencephalon. Interestingly, most of the pathways affected converge at the one controlling cell proliferation thus indicating altered neurogenesis, which was validated using immunohistochemistry for cell proliferation markers BrdU, SOX2, and BLBP. The study concludes that molecules that regulate telencephalon neural progenitor cell proliferation or neurogenesis are crucially involved in chronic stress-induced mood disorders by affecting the circuitry that controls emotion and reward.
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http://dx.doi.org/10.1016/j.pbb.2021.173170DOI Listing
May 2021

Therapeutic angiogenesis using zinc oxide nanoflowers for the treatment of hind limb ischemia in rat model.

Biomed Mater 2021 Mar 3. Epub 2021 Mar 3.

Biomaterials Group, LST Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007, AP, Hyderabad, Andhra Pradesh, 500007, INDIA.

Critical limb ischemia (CLI) is considered as a severe type of peripheral artery diseases (PADs) which occurs due to the inadequate supply of blood to the limb extremities. CLI patients often suffer from extreme cramping pain, impaired wound healing, immobility, cardiovascular complications, amputation of the affected limb and even death. The conventional therapy for the treatment of CLI includes surgical revascularization as well as restoring angiogenesis using growth factor therapy. However, surgical revascularization is suitable for only a minor percentage of CLI patients and it is associated with high perioperative mortality rate. The use of growth factors is also limited in terms of their poor therapeutic angiogenesis potential as observed by the earlier clinical studies, which could be attributed to their poor bio-availability and non-specificity issues. Therefore, to outweigh the aforesaid disadvantages of the conventional strategies, there is an utmost need for the advancement of new alternative therapeutic biomaterials to treat CLI. Since past few decades, various research groups including ours have been involved in developing different pro-angiogenic nanomaterials. Among them, zinc oxide nanoflowers (ZONF), established in our laboratory, are considered as one of the potent nanoparticles to induce therapeutic angiogenesis. In our earlier studies, we have depicted that ZONF promote angiogenesis by inducing the formation of reactive oxygen species (ROS) and nitric oxide (NO) as well as activating Akt/MAPK/eNOS cell signaling pathways in the endothelial cells. Recently, we have also reported the therapeutic potential of ZONF to treat cerebral ischemia through their neuritogenic and neuroprotective properties, exploiting angio-neural cross talk. Considering the excellent pro-angiogenic properties of ZONF and importance of revascularization for the recovery of CLI, in this present study, we have comprehensively explored the therapeutic potential of ZONF in a rat hind limb ischemia model (established by ligating the femoral artery of hind limb), an animal model that mimics CLI in humans. The behavioural studies, laser Doppler perfusion imaging, histopathology, immunofluorescence as well as estimation of serum NO level depicted that the administration of ZONF could ameliorate the ischemic conditions in rats at a faster rate by promoting therapeutic angiogenesis to the ischemic sites. Altogether, the present study offers an alternative nanomedicine approach employing ZONF for the treatment of PADs.
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http://dx.doi.org/10.1088/1748-605X/abebd1DOI Listing
March 2021

Impact of cell wall peptidoglycan O-acetylation on the pathogenesis of Staphylococcus aureus in septic arthritis.

Int J Med Microbiol 2017 Oct 7;307(7):388-397. Epub 2017 Aug 7.

Center for Nanoscience and Molecular medicine, Amrita University, Ponekkara, Cochin, 682041, Kerala, India. Electronic address:

Staphylococcus aureus (S. aureus) is one of the most common pathogen causing septic arthritis. To colonize the joints and establish septic arthritis this bacterium needs to resist the host innate immune responses. Lysozyme secreted by neutrophils and macrophages is an important defense protein present in the joint synovial fluids. S. aureus is known to be resistant to lysozyme due to its peptidoglycan modification by O-acetylation of N-acetyl muramic acid. In this study we have investigated the role of O-acetylated peptidoglycan in septic arthritis. Using mouse models for both local and hematogenous S. aureus arthritis we compared the onset and progress of the disease induced by O-acetyl transferase mutant and the parenteral wild type SA113 strain. The disease progression was assessed by observing the clinical parameters including body weight, arthritis, and functionality of the affected limbs. Further X-ray and histopathological examinations were performed to monitor the synovitis and bone damage. In local S. aureus arthritis model, mice inoculated with the ΔoatA strain developed milder disease (in terms of knee swelling, motor and movement functionality) compared to mice inoculated with the wild type SA113 strain. X-ray and histopathological data revealed that ΔoatA infected mice knee joints had significantly lesser joint destruction, which was accompanied by reduced bacterial load in knee joints. Similarly, in hematogenous S. aureus arthritis model, ΔoatA mutant strain induced significantly less severe clinical septic arthritis compared to its parental strain, which is in accordance with radiological findings. Our data indicate that peptidoglycan O-acetylation plays an important role in S. aureus mediated septic arthritis.
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http://dx.doi.org/10.1016/j.ijmm.2017.08.002DOI Listing
October 2017

A 2-oxa-spiro[5.4]decane scaffold displays neurotrophic, neurogenic and anti-neuroinflammatory activities with high potential for development as a versatile CNS therapeutic.

Sci Rep 2017 05 4;7(1):1492. Epub 2017 May 4.

Chemical Biology, CSIR- Indian Institute of Chemical Technology, Tarnaka, Uppal Road, Hyderabad, 500007, India.

Following our recent discovery of a new scaffold exhibiting significant neurotrophic and neurogenic activities, a structurally tweaked analogue, embodying a 2-oxa-spiro [5.4]decane framework, has been conceptualised and found to be more potent and versatile. It exhibits enhanced neurotrophic and neurogenic action in in vitro, ex vivo and in vivo models and also shows robust neuroprotection in mouse acute cerebral stroke model. The observed attributes are traceable to the predominant activation of the TrkB-PI3K-AKT-CREB pathway. In addition, it also exhibits remarkable anti-neuroinflammatory activity by concurrently down-regulating pro-inflammatory cytokines IL-1α and IL-6, thereby providing a unique molecule with a trinity of neuroactivities, i.e. neurotrophic, neurogenic and anti-inflammatory. The new chemical entity disclosed here has the potential to be advanced as a versatile therapeutic molecule to treat stroke, depression, and possibly other neuropsychiatric disorders associated with attenuated neurotrophic/ neurogenic activity, together with heightened neuroinflammation.
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http://dx.doi.org/10.1038/s41598-017-01297-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431446PMC
May 2017