Scientific Staff

Dr. Rajnish Kumar Chaturvedi
Senior Scientist
System Toxicology & Health Risk Assessment
CSIR-Indian Institute of Toxicology Research
Vishvigyan Bhawan, 31, Mahatma Gandhi Marg
Lucknow - 226 001. Uttar Pradesh, India.
Email: rajnish[at]iitr[dot]res[dot]in | Alternate Email: itrcrajnish@gmail.com
Tel: +91-522-2217497 | Extension: 0522-2217655
Fax: 522-2628227
Area of Specialization
Biochemical and Molecular Neurotoxicology, Neural Stem Cell Biology, Regenerative medicine and neurodegenerative disorders, Cellular and Molecular Mechanism of Parkinson and Huntington Disease
Current R&D/S&T Activities
            Research Interest:
 
  • Normal brain development also referred as neurogenesis, involves a balance between Neural Stem Cell (NSC) proliferation, their migration to different parts of the brain followed by differentiation to neurons,     astrocytes and oligodendrocytes. For optimum brain development newly generated neurons move along precise pathways from their points of origin to their assigned locations, establish synapses with each other, and communicate via these synapses. Several environmental toxicants are reported to cause developmental neurotoxicity in both children and adults. We are trying to understand how environmental toxicants (pesticides and xenoestrogen) affect key events of neurogenesis including regulatory cell signaling pathways. Further, we are involved to assess the molecular and/or cellular events that are target(s) for inhibition of neurogenesis.
  • Use of human and rodent Neural Stem Cells as an alternate in vitro model to assess the neurotoxic potential of environmental contaminants.
  • To assess the cellular and molecular mechanism of neurodegenerative disorders specially Parkinson’s disease, and how environmental toxicants modulate the disease pathogenesis.
  • Identification of novel molecular therapeutic targets in neurodegenerative disorders.
  • Identification of molecules which can induce "BRAIN SELF REPAIR" by actviating resident Neural Stem Cell Population.
 
 
Significant contributions:
 
Ø  Environmental contaminants alter regulatory dynamics of hippocampal neurogenesis through interfering cell signaling: Bisphenol-A (BPA), an environmental xenoestrogenic endocrine disruptor and component of plastic baby feeding bottles and food cans, poses a serious health hazards among the children and pregnant women. We have identified that BPA and carbofuran a carbamate pesticide inhibits the ability of NSC proliferation and differentiation in neurons in the brain leading to cognitive dysfunction and Alzheimer’s disease like phenotypes (Mishra et al., 2012; Toxicological Sciences,  Tiwari et al., 2014a,b, 2015; Molecular Neurobiology, Seth et al., 2017, Journal of Biological Chemistry, 2017 Nov 24;292(47):19423-19440). Studies carried out by my group first time suggested significant inhibitory effects of BPA on NSC proliferation and neuronal differentiation in the rat via the Wnt/β-catenin signaling pathway (Tiwari et al., 2014a,b Molecular Neurobiology). BPA exposure both during prenatal and postnatal periods alters myelination in the hippocampus of the rat brain leading to cognitive deficits (Tiwari et al., 2015; Molecular Neurobiology).
 
Ø  Autophagy could be an imperative biological marker for neurotoxicity of BPA: Recently, we deciphered the detailed mechanism of effects of BPA on autophagy, and association with neurodegenerative changes as observed in Alzheimer’s disease. Activation of autophagy against BPA resulted intracellular energy sensor AMPK activation, increased phosphorylation of raptor, and decreased phosphorylation of ULK1 (Ser757), and silencing of AMPK exacerbated BPA neurotoxicity. These results suggest implication of autophagy against BPA mediated neurodegeneration through involvement of AMPK and mTOR pathways. Hence, autophagy which arbitrates cell survival and demise during stress conditions may serve as biomarker of xenoestrogen exposure (Agarwal et al., Journal of Biological Chemistry, 2015, 21; 290(34):21163-84).
                  Further, our studies suggested that chronic exposure of BPA, impaired autophagy-mediated mitochondrial turnover, leading to mitochondrial fragmentation, increased levels of Drp-1 (dynamin-related protein 1) and enhanced Drp-1 mitochondrial translocation. Pharmacological (Mdivi-1) and genetic (Drp-1siRNA) inhibition of Drp-1 reversed BPA-induced mitochondrial dysfunctions and fragmentation. These studies implicate Drp-1 as a potential therapeutic target against BPA-mediated impaired mitochondrial dynamics and neurodegeneration in the hippocampus. (Agarwal et al., Journal of Biological Chemistry, 2016, Jul 29;291(31):15923-39).
 
Ø  Epileptic drug ethosuximide enhances neurogenesis and reverses cognitive dysfunctions in rat model of Alzheimer’s disease: Neurogenesis involves generation of new neurons through neural stem cells (NSC) proliferation, migration, and neuronal differentiation in the hippocampus. Adult hippocampal neurogenesis is involved in cognitive functions and reduced in Alzheimer’s disease (AD). Ethosuximide (ETH), an anticonvulsant drug is used for the treatment of epileptic seizure. We demonstrated that ETH promotes hippocampal neurogenesis in adult rats, and reverses the learning and memory deficits characterizing Aβ rat model of AD like phenotypes. ETH acts through PI3K/AKT/Wnt/β-catenin signaling pathway to induce neurogenesis. Given these findings, it is suggested that ETH may promote regeneration of NSC pool, induce neurogenesis, and provide therapeutic benefits in patients of AD (Tiwari et al., Journal of Biological Chemistry, 2015, 20;290 (47):28540-58).
 
Ø  Induction of Brain Self repair mechanism for therapeutic benefits in Alzheimer’s disease:  Neurogenesis, is reported to be reduced in Alzheimer’s disease (Tiwari et al., 2014, Molecular Neurobiology). We induced the endogenous “Brain Self Repair” by activating existing neurogenesis using neuroprotective factors in the environmental toxicants exposed rodent brain and rodent model of Alzheimer’s disease (Tiwari et al., 2015, Molecular Neurbiology; Tiwari et al., ACS NANO. 2014 Jan 28;8(1):76-103,). We have first time studied the role of curcumin on induction of neurogenesis in Alzheimer’s disease. We also developed a novel strategy to differentiate neural stem cells into neurons using curcumin. My group also first time identified that curcumin interacts with three novel molecular targets viz. Wif-1, Dkk and GSK-3β.
 
Ø  Nanoparticle mediated delivery of otherwise blood brain barrier impermeable drug dopamine in Parkinson’s disease: 
Sustained and safe delivery of neurotransmitter dopamine across the blood brain barrier (BBB) is a major hurdle for successful therapy in Parkinson's disease (PD), a neurodegenerative disorder. We designed dopamine-loaded PLGA nanoparticles (DA NPs) to deliver dopamine to the brain. These nanoparticles were able to cross the BBB, and slowly and constantly released dopamine in the striatum in a 6-hydroxydopamine (6-OHDA)-induced rat model of PD. Systemic intravenous administration of DA NPs caused significantly increased levels of dopamine in the striatum of parkinsonian rats. DA NPs significantly recovered neurobehavioral abnormalities in 6-OHDA-induced parkinsonian rats. (Pahuja et. al., ACS NANO. 2015, 26;9 (5):4850-71).
Partial List of Research Publications
Awards/Honours/ Distinctions
Awards:


 

No.

Award

Year

Details

1.

Elected member of Indian National Young Academy of Sciences of INSA-MINYAS

2018

Indian National Young Academy of Sciences of INSA

2.

DBT National Bioscience Award

2016

Department of Biotechnology, India

3.

OPPI Young Scientist Award-2016

2016

Organizers of Pharmaceutical Producers of India (OPPI)

4.

Shri Om Prakash Sharma Young Scientist Award in Biomedical Research

2015

Indian Academy of Biomedical Sciences

5.

NASI-Scopus Young Scientist Award-2015 in the area of Medicine.

2015

National Academy of Sciences-India and Elsevier-India

6.

Lady Tata Memorial Young Scientist Award-2014 in the area of Medical Sciences.

2014

Lady Tata Memorial Trust-United Kingdom

7.

Elected member of National Academy of Sciences, Allahabad- (MNASI)

2013

National Academy of Sciences, Allahabad

8.

National Academy of Sciences (NASI) Young Scientist Award-2013 in the area of Biochemistry, Biotechnology and Bio-Medical Sciences.

2013

National Academy of Sciences, Allahabad-India

9.

Indian National Science Academy (INSA) Young Scientist Award-2012 in the area of Health Sciences.

2012

Indian National Science Academy-New Delhi

10

Gauri Ganguly Memorial Young Scientist Award-2012 of Biomedical Sciences.

2012

Indian Science Congress Association (ISCA), Kolkata

11.

Best Published Paper Award

2012

CSIR-Indian Institute of Toxicology Research, Lucknow

12.

Lucknow Youth Icons Award-2009 in the field of Science.

2009

Social Environmental & Educational Development Society

13.

U.P. Council of Science and Technology Young Scientist Award-2006

2006

U.P. Council of Science and Technology

14.

First place in “Parkinson’s Disease Quiz Contest

2005

Novartis Pharma, during 16th International Congress on Parkinson’s disease, 5 -9 June 2005, at Berlin-Germany.

15.

Best paper award

2004

Federation of Asian-Oceanic Neuroscience Societies (FAONS), during 2nd FAONS Symposium, 17-19 May, 2004, at Tehran, Iran.

16.

Best paper award

2003

National Brain Research Centre (NBRC) during International conference on Theoretical Neurobiology, 24-27 Feb 2003 at NBRC, New Delhi.

17.

Best paper award

2002

National Brain Research Centre, during INDO-US colloquium on Brain Research, 10-12 Jan 2002 at New Delhi-India.

 


Member of International/National Societies and Academies:

  1. Elected Member of National Academy of Sciences (NASI)- Allahabad.
  2. Elected member of Indian National Young Academy of Sciences of INSA-New Delhi, (INYAS)- MINYAS-2018
  3. Society for Neuroscience (SFN)-USA
  4. Society of Toxicology-USA
  5. New York Academy of Sciences (NYAS)-USA
  6. International Society of Neurochemistry (ISN)
  7. International Society of Developmental Neuroscience (ISDN)
  8. International Neurotoxicology association (INA)
  9. International Society of Autonomic Nervous System (ISAN)
  10. International Brain Research Organization (IBRO)
  11. Indian Academy of Neurosciences (IAN)
  12. Molecular and Cellular Cognition Society (MCCS)
  13. Asian Pacific Society of Neurochemistry (APSN)


Editorial Board Member:


  1. Research and Reviews: Journal of Toxicology
  2. International Journal of Neuropathology
  3. Advances in Parkinson’s Disease
  4. BioMed Research International
  5.  Evidence Based Complementary and Alternative Medicine
  6. Neural Plasticity
  7. Journal of Chemical Neuroanatomy
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