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Article ; Online: Differential binding of CREB and REST/NRSF to NMDAR1 promoter is associated with the sex-selective cognitive deficit following postnatal PBDE-209 exposure in mice.

Gupta, Priya / Gupta, Rajaneesh K / Gandhi, Behrose S / Singh, Poonam

Environmental science and pollution research international

2023

Abstract: Neonatal exposure to decabromodiphenyl ether (PBDE-209), a widely used flame retardant, affects cognitive performances in the later stage of life in a sex-dependent manner. PBDE-209 interferes with glutamatergic signaling and N-methyl-D-aspartate ... ...

Abstract	Neonatal exposure to decabromodiphenyl ether (PBDE-209), a widely used flame retardant, affects cognitive performances in the later stage of life in a sex-dependent manner. PBDE-209 interferes with glutamatergic signaling and N-methyl-D-aspartate receptor (NMDAR) subunits with unresolved regulatory mechanisms. This study exposed male and female mice pups through postnatal day (PND) 3-10 to PBDE-209 (oral dose: 0, 6, or 20 mg/kg body weight). The frontal cortex and hippocampus, collected from neonate (PND 11) and young (PND 60) mice, were analyzed for cAMP response element-binding protein (CREB) and RE1-silencing transcription factor/ Neuron-restrictive silencer factor (REST/NRSF) binding to NMDAR1 promoter and expression of NMDAR1 gene by electrophoretic mobility shift assay and semi-quantitative RT-PCR respectively. Behavioral changes were assessed using spontaneous alternation behavior and novel object recognition tests in young mice. In neonates, the binding of CREB was increased, while REST/NRSF was decreased significantly to their cognate NMDAR1 promoter sequences at the high dose of PBDE-209 in both the sexes. This reciprocal pattern of CREB and REST/NRSF interactions correlates with the up-regulation of NMDAR1 expression. Young males followed a similar pattern of CREB and REST/NRSF binding and NMDAR1 expression as in neonates. Surprisingly, young females did not show any alteration when compared to age-matched controls. Also, we found that only young males showed working and recognition memory deficits. These results indicate that early exposure to PBDE-209 interferes with CREB- and REST/NRSF-dependent regulation of the NMDAR1 gene in an acute setting. However, long-term effects persist only in young males that could be associated with cognitive impairment.
Language	English
Publishing date	2023-03-31
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1178791-0
ISSN	1614-7499 ; 0944-1344
ISSN (online)	1614-7499
ISSN	0944-1344
DOI	10.1007/s11356-023-26107-0
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Article ; Online: Drug repurposing for COVID-19 based on an integrative meta-analysis of SARS-CoV-2 induced gene signature in human airway epithelium.

Gupta, Rajaneesh K / Nwachuku, Enyinna L / Zusman, Benjamin E / Jha, Ruchira M / Puccio, Ava M

PloS one

2021 Volume 16, Issue 9, Page(s) e0257784

Abstract: Drug repurposing has the potential to bring existing de-risked drugs for effective intervention in an ongoing pandemic-COVID-19 that has infected over 131 million, with 2.8 million people succumbing to the illness globally (as of April 04, 2021). We have ...

Abstract	Drug repurposing has the potential to bring existing de-risked drugs for effective intervention in an ongoing pandemic-COVID-19 that has infected over 131 million, with 2.8 million people succumbing to the illness globally (as of April 04, 2021). We have used a novel `gene signature'-based drug repositioning strategy by applying widely accepted gene ranking algorithms to prioritize the FDA approved or under trial drugs. We mined publically available RNA sequencing (RNA-Seq) data using CLC Genomics Workbench 20 (QIAGEN) and identified 283 differentially expressed genes (FDR<0.05, log2FC>1) after a meta-analysis of three independent studies which were based on severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection in primary human airway epithelial cells. Ingenuity Pathway Analysis (IPA) revealed that SARS-CoV-2 activated key canonical pathways and gene networks that intricately regulate general anti-viral as well as specific inflammatory pathways. Drug database, extracted from the Metacore and IPA, identified 15 drug targets (with information on COVID-19 pathogenesis) with 46 existing drugs as potential-novel candidates for repurposing for COVID-19 treatment. We found 35 novel drugs that inhibit targets (ALPL, CXCL8, and IL6) already in clinical trials for COVID-19. Also, we found 6 existing drugs against 4 potential anti-COVID-19 targets (CCL20, CSF3, CXCL1, CXCL10) that might have novel anti-COVID-19 indications. Finally, these drug targets were computationally prioritized based on gene ranking algorithms, which revealed CXCL10 as the common and strongest candidate with 2 existing drugs. Furthermore, the list of 283 SARS-CoV-2-associated proteins could be valuable not only as anti-COVID-19 targets but also useful for COVID-19 biomarker development.
MeSH term(s)	Antiviral Agents/therapeutic use ; Drug Evaluation, Preclinical/methods ; Drug Repositioning/methods ; Epithelial Cells/drug effects ; Epithelium/drug effects ; Humans ; Respiratory Mucosa/drug effects ; Respiratory Mucosa/metabolism ; Respiratory Mucosa/virology ; Respiratory System/drug effects ; SARS-CoV-2/drug effects ; SARS-CoV-2/genetics ; SARS-CoV-2/pathogenicity ; COVID-19 Drug Treatment
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2021-09-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0257784
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Article ; Online: Age-Dependent Alterations in the Interactions of NF-κB and N-myc with GLT-1/EAAT2 Promoter in the Pericontusional Cortex of Mice Subjected to Traumatic Brain Injury.

Gupta, Rajaneesh K / Prasad, S

Molecular neurobiology

2016 Volume 53, Issue 5, Page(s) 3377–3388

Abstract: Traumatic brain injury (TBI) is one of the major risk factors of dementia, aging, and cognitive impairments, etc. We have previously reported that expression of the astrocytic glutamate transporter GLT-1/EAAT2 is downregulated in the pericontusional ... ...

Abstract	Traumatic brain injury (TBI) is one of the major risk factors of dementia, aging, and cognitive impairments, etc. We have previously reported that expression of the astrocytic glutamate transporter GLT-1/EAAT2 is downregulated in the pericontusional cortex of adult and old mice in post-TBI time-dependent manner, and the process of decline starts before in old than in adult TBI mice. However, relationship between age- and TBI-dependent alterations in GLT-1/EAAT2 expression and interactions of transcription factors NF-κB and N-myc with their cognate GLT-1/EAAT2 promoter sequences, an important step of its transcriptional control, is not known. To understand this, we developed TBI mouse model by modified chronic head injury (CHI) method, analyzed expression of GFAP, TNF-α, and AQP4 by RT-PCR for its validation, and analyzed interactions of NF-κB and N-myc with GLT-1/EAAT2 promoter sequences by electrophoretic mobility shift assay (EMSA). Our EMSA data revealed that interactions of NF-κB and N-myc with GLT-1/EAAT2 promoter sequences was significantly elevated in the ipsi-lateral cortex of both adult and old TBI mice in post-TBI time-dependent manner; however, these interactions started immediately in the old compared to that in adult TBI mice, which could be attributed to our previously reported age- and post-TBI time-dependent differential expression of GLT-1/EAAT2 in the pericontusional cortex.
Language	English
Publishing date	2016-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	645020-9
ISSN	1559-1182 ; 0893-7648
ISSN (online)	1559-1182
ISSN	0893-7648
DOI	10.1007/s12035-015-9287-y
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Article ; Online: Drug repurposing for COVID-19 based on an integrative meta-analysis of SARS-CoV-2 induced gene signature in human airway epithelium.

Rajaneesh K Gupta / Enyinna L Nwachuku / Benjamin E Zusman / Ruchira M Jha / Ava M Puccio

PLoS ONE, Vol 16, Iss 9, p e

2021 Volume 0257784

Abstract	Drug repurposing has the potential to bring existing de-risked drugs for effective intervention in an ongoing pandemic-COVID-19 that has infected over 131 million, with 2.8 million people succumbing to the illness globally (as of April 04, 2021). We have used a novel `gene signature'-based drug repositioning strategy by applying widely accepted gene ranking algorithms to prioritize the FDA approved or under trial drugs. We mined publically available RNA sequencing (RNA-Seq) data using CLC Genomics Workbench 20 (QIAGEN) and identified 283 differentially expressed genes (FDR<0.05, log2FC>1) after a meta-analysis of three independent studies which were based on severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection in primary human airway epithelial cells. Ingenuity Pathway Analysis (IPA) revealed that SARS-CoV-2 activated key canonical pathways and gene networks that intricately regulate general anti-viral as well as specific inflammatory pathways. Drug database, extracted from the Metacore and IPA, identified 15 drug targets (with information on COVID-19 pathogenesis) with 46 existing drugs as potential-novel candidates for repurposing for COVID-19 treatment. We found 35 novel drugs that inhibit targets (ALPL, CXCL8, and IL6) already in clinical trials for COVID-19. Also, we found 6 existing drugs against 4 potential anti-COVID-19 targets (CCL20, CSF3, CXCL1, CXCL10) that might have novel anti-COVID-19 indications. Finally, these drug targets were computationally prioritized based on gene ranking algorithms, which revealed CXCL10 as the common and strongest candidate with 2 existing drugs. Furthermore, the list of 283 SARS-CoV-2-associated proteins could be valuable not only as anti-COVID-19 targets but also useful for COVID-19 biomarker development.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Microglial-oligodendrocyte interactions in myelination and neurological function recovery after traumatic brain injury.

Song, Shanshan / Hasan, Md Nabiul / Yu, Lauren / Paruchuri, Satya S / Bielanin, John P / Metwally, Shamseldin / Oft, Helena C M / Fischer, Sydney G / Fiesler, Victoria M / Sen, Tanusree / Gupta, Rajaneesh K / Foley, Lesley M / Hitchens, T Kevin / Dixon, C Edward / Cambi, Franca / Sen, Nilkantha / Sun, Dandan

Journal of neuroinflammation

2022 Volume 19, Issue 1, Page(s) 246

Abstract: Differential microglial inflammatory responses play a role in regulation of differentiation and maturation of oligodendrocytes (OLs) in brain white matter. How microglia-OL crosstalk is altered by traumatic brain injury (TBI) and its impact on axonal ... ...

Abstract	Differential microglial inflammatory responses play a role in regulation of differentiation and maturation of oligodendrocytes (OLs) in brain white matter. How microglia-OL crosstalk is altered by traumatic brain injury (TBI) and its impact on axonal myelination and neurological function impairment remain poorly understood. In this study, we investigated roles of a Na
MeSH term(s)	Animals ; Brain Injuries, Traumatic/metabolism ; Disease Models, Animal ; Mice ; Mice, Inbred C57BL ; Microglia/metabolism ; Oligodendroglia ; Recovery of Function ; White Matter
Language	English
Publishing date	2022-10-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2156455-3
ISSN	1742-2094 ; 1742-2094
ISSN (online)	1742-2094
ISSN	1742-2094
DOI	10.1186/s12974-022-02608-6
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Article ; Online: CDRI-08 Attenuates REST/NRSF-Mediated Expression of NMDAR1 Gene in PBDE-209-Exposed Mice Brain

Priya Verma / Rajaneesh K. Gupta / Behrose S. Gandhi / Poonam Singh

Evidence-Based Complementary and Alternative Medicine, Vol

2015 Volume 2015

Keywords	Medicine ; R ; Medicine (General) ; R5-920
Publishing date	2015-01-01T00:00:00Z
Publisher	Hindawi Publishing Corporation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: CDRI-08 Attenuates REST/NRSF-Mediated Expression of NMDAR1 Gene in PBDE-209-Exposed Mice Brain

Priya Verma / Rajaneesh K. Gupta / Behrose S. Gandhi / Poonam Singh

Evidence-Based Complementary and Alternative Medicine, Vol

2015 Volume 2015

Abstract: CDRI-08 is a standardized bacoside enriched ethanolic extract of Bacopa monnieri, a nootropic plant. We reported that CDRI-08 attenuated oxidative stress and memory impairment in mice, induced by a flame retardant, PBDE-209. In order to explore the ... ...

Abstract	CDRI-08 is a standardized bacoside enriched ethanolic extract of Bacopa monnieri, a nootropic plant. We reported that CDRI-08 attenuated oxidative stress and memory impairment in mice, induced by a flame retardant, PBDE-209. In order to explore the mechanism, present study was designed to examine the role of CDRI-08 on the expression of NMDAR1 (NR1) and the binding of REST/NRSF to NR1 promoter against postnatal exposure of PBDE-209. Male mice pups were orally supplemented with CDRI-08 at the doses of 40, 80, or 120 mg/kg along with PBDE-209 (20 mg/kg) during PND 3–10 and frontal cortex and hippocampus were collected at PND 11 and 60 to study the expression and regulation of NR1 by RT-PCR and electrophoretic mobility shift assay, respectively. The findings showed upregulated expression of NR1 and decreased binding of REST/NRSF to NR1 promoter after postnatal exposure of PBDE-209. Interestingly, supplementation with CDRI-08 significantly restored the expression of NR1 and binding of REST/NRSF to NR1 promoter near to the control value at the dose of 120 mg/kg. In conclusion, the results suggest that CDRI-08 possibly acts on glutamatergic system through expression and regulation of NR1 and may restore memory, impaired by PBDE-209 as reported in our previous study.
Keywords	Other systems of medicine ; RZ201-999
Subject code	572
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: CDRI-08 Attenuates REST/NRSF-Mediated Expression of NMDAR1 Gene in PBDE-209-Exposed Mice Brain.

Verma, Priya / Gupta, Rajaneesh K / Gandhi, Behrose S / Singh, Poonam

Evidence-based complementary and alternative medicine : eCAM

2015 Volume 2015, Page(s) 403840

Abstract	CDRI-08 is a standardized bacoside enriched ethanolic extract of Bacopa monnieri, a nootropic plant. We reported that CDRI-08 attenuated oxidative stress and memory impairment in mice, induced by a flame retardant, PBDE-209. In order to explore the mechanism, present study was designed to examine the role of CDRI-08 on the expression of NMDAR1 (NR1) and the binding of REST/NRSF to NR1 promoter against postnatal exposure of PBDE-209. Male mice pups were orally supplemented with CDRI-08 at the doses of 40, 80, or 120 mg/kg along with PBDE-209 (20 mg/kg) during PND 3-10 and frontal cortex and hippocampus were collected at PND 11 and 60 to study the expression and regulation of NR1 by RT-PCR and electrophoretic mobility shift assay, respectively. The findings showed upregulated expression of NR1 and decreased binding of REST/NRSF to NR1 promoter after postnatal exposure of PBDE-209. Interestingly, supplementation with CDRI-08 significantly restored the expression of NR1 and binding of REST/NRSF to NR1 promoter near to the control value at the dose of 120 mg/kg. In conclusion, the results suggest that CDRI-08 possibly acts on glutamatergic system through expression and regulation of NR1 and may restore memory, impaired by PBDE-209 as reported in our previous study.
Language	English
Publishing date	2015-08-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2171158-6
ISSN	1741-4288 ; 1741-427X
ISSN (online)	1741-4288
ISSN	1741-427X
DOI	10.1155/2015/403840
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Article: Accumulation of heavy metals in soil and paddy crop (Oryza sativa), irrigated with water of Ramgarh Lake, Gorakhpur, UP, India

Singh, Jaswant / Upadhyay, Suraj K / Pathak, Rajaneesh K / Gupta, Vidhu

Toxicology and environmental chemistry. 2011 Mar. 1, v. 93, no. 3

2011

Abstract: Heavy metals, a highly polluting group of constituents known to exert adverse effects, tend to accumulate in living organisms. The objective of this study was to determine the accumulation and translocation of heavy metals in soil and in paddy crop ... ...

Abstract	Heavy metals, a highly polluting group of constituents known to exert adverse effects, tend to accumulate in living organisms. The objective of this study was to determine the accumulation and translocation of heavy metals in soil and in paddy crop irrigated with lake water compared to soil and paddy crop irrigated with bore-well water. The quantities of heavy metals (Cd, Cr, Cu, Pb, Zn, As, Mn, and Hg) were determined in different parts of rice plants (Oryza sativa). Results revealed that the mean levels of soil Cd, Cr, Pb, Zn, As, Mn, and Hg in experimental soil and in different parts of rice plant (root, straw, and grain) were higher than the control except for Cu. The content of eight toxic metals was significantly higher in root than in aerial parts of the rice (straw and grains). Rice roots were enriched in Cd, As, Hg, and Pb from the soil, while Cr, Cu, Zn, and Mn were hardly taken by the roots. Bioaccumulation factor for Hg was significantly higher than other heavy metals. Metal transfer factors from soil to rice plants were significant for Cd, Cr, Cu, Pb, Zn, As, Mn, and Hg. The concentrations of metals in lake water were found to be within the permissible limit of Indian standard prescribed by Central Pollution Control Board (2000), except for Hg and As, which were higher than the limit of Indian standard. However, the concentrations of heavy metals in soil and rice grains were still below the maximal levels, as stipulated by Indian Prevention of Food Adulteration Act (PFA, 1954) and World Health Organization (WHO, 1993) guidelines.
Keywords	Oryza sativa ; World Health Organization ; adulterated products ; adverse effects ; aerial parts ; arsenic ; bioaccumulation factor ; cadmium ; chromium ; copper ; guidelines ; heavy metals ; irrigated farming ; irrigation water ; lakes ; laws and regulations ; lead ; manganese ; mercury ; paddy soils ; pollution control ; rice ; rice soils ; roots ; straw ; toxicity ; translocation (plant physiology) ; zinc ; India
Language	English
Dates of publication	2011-0301
Size	p. 462-473.
Publishing place	Taylor & Francis Group
Document type	Article
ZDB-ID	2038336-8
ISSN	1029-0486 ; 0277-2248 ; 0092-9867
ISSN (online)	1029-0486
ISSN	0277-2248 ; 0092-9867
DOI	10.1080/02772248.2010.546559
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Glial molecular alterations with mouse brain development and aging: up-regulation of the Kir4.1 and aquaporin-4.

Gupta, Rajaneesh Kumar / Kanungo, Madhusudan

Age (Dordrecht, Netherlands)

2011 Volume 35, Issue 1, Page(s) 59–67

Abstract: ... of extracellular K(+) and water from the synaptic layers. However, it is still unclear whether there is ... expression pattern suggests that Kir4.1 and AQP4 channels may play an important role in brain K(+) and water ... homeostasis. In adult mouse brain, inwardly rectifying K+ (Kir4.1) and aquaporin-4 (AQP4) channels localize ...

Abstract	Glial cells, besides participating as passive supporting matrix, are also proposed to be involved in the optimization of the interstitial space for synaptic transmission by tight control of ionic and water homeostasis. In adult mouse brain, inwardly rectifying K+ (Kir4.1) and aquaporin-4 (AQP4) channels localize to astroglial endfeets in contact with brain microvessels and glutamate synapses, optimizing clearance of extracellular K(+) and water from the synaptic layers. However, it is still unclear whether there is an age-dependent difference in the expressions of Kir4.1 and AQP4 channels specifically during postnatal development and aging when various marked changes occur in brain and if these changes region specific. RT-PCR and immunoblotting was conducted to compare the relative expression of Kir4.1 and AQP4 mRNA and protein in the early and mature postnatal (0-, 15-, 45-day), adult (20-week), and old age (70-week) mice cerebral and cerebellar cortices. Expressions of Kir4.1 and AQP4 mRNA and protein are very low at 0-day. A pronounced and continuous increase was observed by mature postnatal ages (15-, 45-days). However, in the 70-week-old mice, expressions are significantly up-regulated as compared to 20-week-old mice. Both genes follow the same age-related pattern in both cerebral and cerebellar cortices. The time course and expression pattern suggests that Kir4.1 and AQP4 channels may play an important role in brain K(+) and water homeostasis in early postnatal weeks after birth and during aging.
MeSH term(s)	Aging/genetics ; Animals ; Brain/growth & development ; Electrophoresis, Polyacrylamide Gel ; Male ; Mice ; Mice, Inbred AKR ; Neuroglia/metabolism ; Potassium Channels, Inwardly Rectifying/biosynthesis ; Potassium Channels, Inwardly Rectifying/genetics ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Up-Regulation
Chemical Substances	Kcnj10 (channel) ; Potassium Channels, Inwardly Rectifying ; RNA, Messenger
Language	English
Publishing date	2011-11-06
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	423714-6
ISSN	1574-4647 ; 0161-9152
ISSN (online)	1574-4647
ISSN	0161-9152
DOI	10.1007/s11357-011-9330-5
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