Publications by authors named "Tapatee Das"

8 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

Differential modulation of GR signaling and HDACs in the development of resilient/vulnerable phenotype and antidepressant-like response of vorinostat.

Psychoneuroendocrinology 2021 02 1;124:105083. Epub 2020 Dec 1.

Applied Biology Division, CSIR- Indian Institute of Chemical Technology (IICT), Hyderabad 500007, Telangana, India. Electronic address:

The present study explored the antidepressant potential of vorinostat (VOR) against chronic social defeat stress (CSDS) in mice. Since this model has the remarkable capacity to delineate the resilient and the defeated mice, we also looked for their molecular deviations. Defeated mice showed classical phenotypic alterations such as anhedonia, social avoidance, anxiety and despair. Whereas, resilient mice were immune to the development of those. Both defeated and resilient mice demonstrated marked CORT elevation in blood. Development of resilience vs. defeat to CSDS was found to be associated with the differential nuclear levels of GR, HDAC3 and HDAC6 in the hippocampus. Activation of a stress responsive adaptive mechanism involving these mediators at the nuclear level might be offering resilience while maladaptive mechanisms leading to defeat. Interestingly, an elevated hippocampal HDAC6 level in defeated mice was also observed, which was restored by VOR treatment. Further studies will be necessary to delineate the HDAC6 associated antidepressant mechanisms. As HDAC3 and HDAC6 are crucial mediators of GR signaling, further molecular studies may aid in understanding the basis of development of resilience to target MDD with new prospective.
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http://dx.doi.org/10.1016/j.psyneuen.2020.105083DOI Listing
February 2021

Molecular Basis of Sex Difference in Neuroprotection induced by Hypoxia Preconditioning in Zebrafish.

Mol Neurobiol 2020 Dec 29;57(12):5177-5192. Epub 2020 Aug 29.

Applied Biology, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad, India.

Hypoxia, the major cause of ischemic injury, leads to debilitating disease in infants via birth asphyxia and cerebral palsy, whereas in adults via heart attack and stroke. A widespread, natural protective phenomenon termed 'hypoxic preconditioning' (PH) occurs when prior exposures to hypoxia eventually result in robust hypoxia resistance. Accordingly, we have developed and optimized a novel model of hypoxic preconditioning in adult zebrafish to mimic the tolerance of mini stroke(s) in human, which appears to protect against the severe damage inflicted by a major stroke event. Here, we observed a remarkable difference in the progression pattern of neuroprotection between preconditioning hypoxia followed by acute hypoxia (PH) group, and acute hypoxia (AH) only group, with noticeable sex difference when compared with normoxia behaviour upon recovery. Since gender difference has been reported in stroke risk factors and disease history, it was pertinent to investigate whether any such sex difference also exists in PH's protective mechanism against acute ischemic stroke. In order to elucidate the neural molecular mechanisms behind sex difference in neuroprotection induced by PH, a high throughput proteomics approach utilizing iTRAQ was performed, followed by protein enrichment analysis using ingenuity pathway analysis (IPA) tool. Out of thousands of significantly altered proteins in zebrafish brain, the ones having critical role either in neuroglial proliferation/differentiation or neurotrophic functions were validated by analyzing their expression levels in preconditioned (PH), acute hypoxia (AH), and normoxia groups. The data indicate that female zebrafish brains are more protected against the severity of AH when exposed to the hypoxic preconditioning. The study also sheds light on the involvement of many signalling pathways underlying sex difference in preconditioning-induced neuroprotective mechanism, which can be further validated for the therapeutic approach.
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http://dx.doi.org/10.1007/s12035-020-02091-1DOI Listing
December 2020

Potential Therapeutic Application of Zinc Oxide Nanoflowers in the Cerebral Ischemia Rat Model through Neuritogenic and Neuroprotective Properties.

Bioconjug Chem 2020 03 25;31(3):895-906. Epub 2020 Feb 25.

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

Neuritogenesis, a complex process of the sprouting of neurites, plays a vital role in the structural and functional restoration of cerebral ischemia-injured neuronal tissue. Practically, there is no effective long-term treatment strategy for cerebral ischemia in clinical practice to date due to several limitations of conventional therapies, facilitating the urgency to develop new alternative therapeutic approaches. Herein, for the first time we report that pro-angiogenic nanomaterials, zinc oxide nanoflowers (ZONF), exhibit neuritogenic activity by elevating mRNA expression of different neurotrophins, following PI3K/Akt-MAPK/ERK signaling pathways. Further, ZONF administration to global cerebral ischemia-induced Fischer rats shows improved neurobehavior and enhanced synaptic plasticity of neurons via upregulation of Neurabin-2 and NT-3, revealing their neuroprotective activity. Altogether, this study offers the basis for exploitation of angio-neural cross talk of other pro-angiogenic nano/biomaterials for future advancement of alternative treatment strategies for cerebral ischemia, where neuritogenesis and neural repair are highly critical.
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http://dx.doi.org/10.1021/acs.bioconjchem.0c00030DOI Listing
March 2020

Revealing sex-specific molecular changes in hypoxia-ischemia induced neural damage and subsequent recovery using zebrafish model.

Neurosci Lett 2019 11 10;712:134492. Epub 2019 Sep 10.

Applied Biology, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, U.P, India. Electronic address:

Functional recovery from hypoxia-ischemia depends on an individual's response to the ischemic damage and recovery. Many of the neurological disorders, including cerebral stroke have sex-specific characteristics. Deciphering the differential molecular mechanisms of sex-specific recovery from hypoxic-ischemic insult can improve medical practice in the treatment of cerebral stroke. In the present study, we describe the establishment of a sex-specific global hypoxia-ischemia neural damage and repair model in zebrafish. During hypoxic exposure a delayed behavioural response was observed in female fish that resumed normal swimming pattern earlier than their male counterparts. Moreover, female appeared more affected as they showed restricted locomotor and exploratory behaviour in novel tank test, reduced mitochondrial enzyme activity, enhanced DNA damage, and cell death after hypoxia insult. However, they showed a faster recovery as compared to male. Analysis of mRNA and protein expression levels of some characteristic hypoxic-ischemic markers showed notable sex-specific differences. Using zebrafish model, we have uncovered cellular and molecular differences in sex-specific systemic responses during the post-hypoxia recovery. This insight might help in devising better therapeutic strategy for stroke in female patients.
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http://dx.doi.org/10.1016/j.neulet.2019.134492DOI Listing
November 2019

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-1╬▒ 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

A novel natural product inspired scaffold with robust neurotrophic, neurogenic and neuroprotective action.

Sci Rep 2015 Sep 21;5:14134. Epub 2015 Sep 21.

CSIR- Centre for Cellular and Molecular Biology, Habsiguda, Uppal Road, Hyderabad 500007, India.

In search for drugs to treat neuropsychiatric disorders wherein neurotrophic and neurogenic properties are affected, two neurotrophically active small molecules specially crafted following natural product leads based on 2-oxa-spiro[5.5]-undecane scaffold, have been thoroughly evaluated for their neurotrophic, neurogenic and neuroprotective potential in ex vivo primary culture and in vivo zebrafish and mouse models. The outcome of in vivo investigations suggest that one of these molecules is more neurotrophic than neurogenic while the other one is more neurogenic than neurotrophic and the former exhibits remarkable neuroprotection in a mouse acute ischemic stroke model. The molecular mechanisms of action of these compounds appear to be through the TrkB-MEK-ERK-CREB-BDNF pathway as pre-treatment with neurotrophin receptor TrkB inhibitor ANA-12 and MEK inhibitor PD98059 attenuates the neurotrophic action of compounds.
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http://dx.doi.org/10.1038/srep14134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4585672PMC
September 2015

Chronic unpredictable stress (CUS)-induced anxiety and related mood disorders in a zebrafish model: altered brain proteome profile implicates mitochondrial dysfunction.

PLoS One 2013 14;8(5):e63302. Epub 2013 May 14.

Chemical Biology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad, India.

Anxiety and depression are major chronic mood disorders, and the etiopathology for each appears to be repeated exposure to diverse unpredictable stress factors. Most of the studies on anxiety and related mood disorders are performed in rodents, and a good model is chronic unpredictable stress (CUS). In this study, we have attempted to understand the molecular basis of the neuroglial and behavioral changes underlying CUS-induced mood disorders in the simplest vertebrate model, the zebrafish, Danio rerio. Zebrafish were subjected to a CUS paradigm in which two different stressors were used daily for 15 days, and thorough behavioral analyses were performed to assess anxiety and related mood disorder phenotypes using the novel tank test, shoal cohesion and scototaxis. Fifteen days of exposure to chronic stressors appears to induce an anxiety and related mood disorder phenotype. Decreased neurogenesis, another hallmark of anxiety and related disorders in rodents, was also observed in this zebrafish model. The common molecular markers of rodent anxiety and related disorders, corticotropin-releasing factor (CRF), calcineurin (ppp3r1a) and phospho cyclic AMP response element binding protein (pCREB), were also replicated in the fish model. Finally, using 2DE FTMS/ITMSMS proteomics analyses, 18 proteins were found to be deregulated in zebrafish anxiety and related disorders. The most affected process was mitochondrial function, 4 of the 18 differentially regulated proteins were mitochondrial proteins: PHB2, SLC25A5, VDAC3 and IDH2, as reported in rodent and clinical samples. Thus, the zebrafish CUS model and proteomics can facilitate not only uncovering new molecular targets of anxiety and related mood disorders but also the routine screening of compounds for drug development.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0063302PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653931PMC
December 2013