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1 Curriculum Vitae Jyoti Parkash, Ph.D. Postdoctoral Fellow Jean-Pierre Aubert Research Center INSERM U837 1, place de Verdun 59045 Lille cedex France Education Degree College/University E-mail: [email protected] [email protected] Phone: +33-751048184 Subjects Year of passing Percentage/ Division B.Sc. Himachal Pradesh, University, Shimla Himachal Pradesh, India Chemistry, Botany, Zoology 2000 66.29/1st M.Sc. Guru Nanak Dev University, Amritsar, Punjab, India Guru Nanak Dev University, Amritsar, Punjab, India Zoology 2002 66.5/1st Animal Biotechnology (Neurosciences) 2007 Ph.D. Professional Experience 03/ 2011 – Present Post Doctoral Fellow, INSERM Jean-Pierre Aubert Research Center U837, Development and Plasticity of the Postnatal Brain, NEUROBESE International Associated Laboratory, Place de Verdun, 59045, Lille Cedex, France 02/ 2010 – 02/ 2011 Post Doctoral Fellow, Dipartimento di Biologia Animale e dell’ Uomo, Torino, Italy 01/ 2008 – 01/ 2010 Post Doctoral Fellow, INSERM Jean-Pierre Aubert Research Center U837, Team 2, Development and Plasticity of the Postnatal Brain, NEUROBESE International Associated Laboratory, Place de Verdun 59045 Lille Cedex, France 11/ 2002 – 12/ 2007 Ph.D. (Junior/senior research fellow), Department of Biotechnology, Guru Nanak Dev University, Amritsar, India Jyoti Parkash ([email protected]) 2 Ph.D. Dissertation Title: “Neuronal Plasticity in Adult Brain: Study of Molecular Marker of Synaptic Remodeling in Hypothalamic GnRH- Astroglial cells” Although it is now clear that glia-to neuron communication systems are important components of the central neuroendocrine process controlling mammalian reproduction, the precise mechanisms by which morphological changes are promoted at the median eminence, which is the termination field of those neurons secreting gonadotropin releasing hormone (GnRH) and the communications pathways that specifically link glia and neuron remodeling await further elucidation. This neuronal and glial remodeling is reversed upon cessation of stimulation. Such an activity-dependent structural plasticity illustrates, therefore, both a network and cellular adaptation to increased hormone demand and offers a striking example that dynamic changes in the morphology of adult neurons and glial are intimately related to normal neuronal function. We use GnRH system as model to study Cellular and Molecular mechanish of synaptic remodeling in hypothalamic GnRH system and we determined that The enhanced expression of PSA-NCAM on GnRH neuron terminals and astrocytes in the median eminence region of hypothalamus before the surge release of GnRH observed in proestrous phase suggests that PSA-NCAM plays a permissive role to reduce glial coverage of GnRH terminals. Since PSA is a dynamically regulated product of post-translational modification of NCAM by enzyme polysialyltransferase (PST), we have further ascertained that GnRH neuron in vivo shows changes in PST expression during the proestrous and diestrous phases by ISH and northern blotting techniques. Awards and Fellowships Successful Travel award for 7th International congress of Neuroendocrinology, Rouen, France from 11th - 15th July, 2010. Successful Travel award for the 36th Colloque society de Neuroendocrinology (SNE) international congress from 15th - 18th September, 2009 Nice, France. Invited as speaker in workshop on “Basic Neurochemical Techniques for Young Neuroscientists” (17th - 27th November, 2008) and International symposium on “Molecular Aspects of Brain Aging and Neurological Disorders” (28th - 29th November, 2008) in Department of Biotechnology, Guru Nanak Dev University, Amritsar, India. Best Presentation Award in International symposium on “Molecular Aspects of Brain Aging and Neurological Disorders” (28th - 29th November, 2008) in Department of Biotechnology, Guru Nanak Dev University Amritsar, INDIA. Successful Travel award for attending 7th Biennial Meeting of the Asian Pacific Society for Neurochemistry (APSN) from 2nd - 5th July, 2006, National University Singapore (NUS), Singapore. Jyoti Parkash ([email protected]) 3 Successful Travel award for IBRO-Neuroscience Training School at National University Singapore (NUS), Singapore from 26th - 30th June, 2006. Successful Travel award for 29th Annual Japan Neuroscience Society (JNS) from 19th - 21st July, 2006, Kyoto, Japan. Successful travel award for 2nd Special Conference of the International Society of Neurochemistry on Neural Glycoproteins and Glycolipids, 1st - 5th December, 2006, Antigua, West Indies, Caribbean. Successful Travel award from Indian Academy of Neuroscience to attend the XXII annual meeting from 28th - 30th January, 2005, Gwalior, India. Qualified National Eligibility Test (NET) to pursue doctoral research, 2000 and 2001. Qualified Graduate Aptitude Test of Engineering (GATE) 2000, to pursue doctoral research. Membership of Professional Bodies International Society of Neurochemistry (ISN). International society for development Neuroscience (ISDN) Asian Pacific Society for Neurochemistry (APSN) Japan Neuroscience Society (JNS) Indian Society for Neurochemistry (ISNC) Indian Academy of Neurosciences International congress of Neuroendocrinology (ICN) Society for Neurosciences (SFN) Society for Neuroendocrinology (SNE) Editor of IJBPAS (International Journal of Biology, Pharmaceutical and Allied Sciences Extracurricular Activities Participated in the 7th International Congress of Neuroendocrinology, Rouen, France from 11th - 15th July 2010. Participated in the 14th LARC Neuroscience meeting on 29th October 2010, Lille. Participated in the 36th Colloque De la societie de neuroendocrinologie (SNE) international congress from 15th - 18th September, 2009 Nice, France. Two years regular participant in National service Scheme (NSS) and attended 10 days National camp in NSS from 11th - 20th January, 1999 under the theme Youth for Community Development. 1st in Quiz competition (senior level) conducted under National Environment Awareness Campaign of the Union Ministry of Environment and Forest, 2002, Guru Nanak Dev University, Amritsar. Workshops Attended IBRO-Neuroscience Training School at National University Singapore (NUS), Singapore from 26th - 30th June, 2006. Attended workshop on “Tools for Bio-informatics Sub-center, Department of Biotechnology, Guru Nanak Dev University, Amritsar from 3rd - 4th March, 2005. Jyoti Parkash ([email protected]) 4 Publications (1) Jyoti Parkash and Gurcharan Kaur 2005: Neuronal-Glial Plasticity in the GnRH Release in Adult Female Rats: Role of Polysialylated Form of Neural Cell Adhesion Molecule. Journal of Endocrinology (impact factor: 3.548) 186: 397-409. (2) Jyoti Parkash and Gurcharan Kaur 2007: Potential of PSA-NCAM in neuron-glial plasticity in the adult hypothalamus: Role of noradrenergic and GABAergic neurotransmitters. Brain Research Bulletin (impact factor: 2.818) 74(5): 317-328. (3) Jyoti Parkash and Gurcharan Kaur 2007: Transcriptional Regulation of PSA-NCAM Mediated Neuron-glial Plasticity in the Adult Hypothalamus. Neuron Glia Biology (impact factor: 2.611) 3: 299-307. (4) Jyoti Parkash, Sushil Kumar, Herdeep Kumar and Gurcharan Kaur 2009: Interactive effect of excitotoxic injury and dietary restriction on neurogenesis and neurotrophic factors in adult male rat brain. Neuroscience Research (impact factor: 2.376) 65(4): 367-374. (5) Jyoti Parkash, , Xavier d’Anglemont de Tassigny, Nicole Bellefontaine, Celine Campagne, Danièle Mazure, Valérie Buée-Scherrer, and Vincent Prevot 2010: Phosphorylation of N-methyl-D-aspartic acid receptor-associated neuronal nitric oxide synthase depends on estrogens and modulates hypothalamic nitric oxide production during the ovarian cycle. Endocrinology (impact factor: 5.12) 151: 2723 - 2735. (6) Jyoti Parkash and Gurcharan Kaur 2010: Steroid Hormones Regulate Post-Translational Modification of Neural Cell Adhesion Molecule: Implication For The Neuroendocrine Control of GnRH. Journal of Neurological Sciences 27(2): 197-213. (7) Vincent Prevot, Naresh Kumar Hanchantae, Arian Shrif, Jyoti Parkash, Cecilia Estrella, Cécile Allet, Celine Campagne, Sandrine de Seranno, Xavier d’Anglemont de Tassigny, Marc Beronni 2010: Structural plasticity in GnRH system. Frontier in Neuroendocrinology (impact factor: 12.067) 31 (3): 241-258. (8) Vincent Prevot, Bellefontaine N, Marc Beronni, Arian Shrif, Naresh Kumar Hanchantae, Jyoti Parkash, Celine Campagne, Sandrine de Seranno 2010: GnRH nerve terminals, tanycytes and neurohaemal junction remodeling in the adult median eminence: functional consequences for reproduction and dynamic role of vascular endothelial cells. Journal of Neuroendocrinology (impact factor: 4.67) 22 (7): 639-649. (9) Bellefontaine N, Naresh Kumar Hanchantae, Jyoti Parkash, Celine Campagne, Sandrine de Seranno, Jérôme Clasadonte, Xavier d’Anglemont de Tassigny, Vincent Prevot 2011: Nitric oxide as key mediator of neuron-to-neuron and endothelia-to-glia communication involved in the neuroendocrine control of reproduction. Neuroendocrinology (impact factor: 3.272) 93: 74-89. (10) Víctor Briz, Jyoti Parkash, Sara Sánchez-Redondo, Vincent Prevot, Cristina Suñol 2011: Allopregnanolone Prevents Dieldrin-induced NMDA Receptor Internalization and Neurotoxicity in Cortical Neurons by Preserving GABAa Receptor Functionality. Endocrinology (impact factor: 5.12) 153(2): 847-60. (11) Jyoti Parkash, Naresh Kumar Hanchantae (Equally contributed), Daniel Mazure, Xavier d’Anglemont de Tassigny, Vincent Prevot 2012: Kisspeptin-GPR54 signaling in mouse NOsynthesizing neurons participates in the hypothalamic control of ovulation. Journal of Neuroscience (impact factor: 7.93) 32(3): 932-945. (12) Sushil Kumar, Jyoti Parkash, Herdeep Kumar and Gurcharan Kaur 2012: Enzymatic removal of polysialic acid from neural cell adhesion molecule interrupts gonadotropin releasing hormone (GnRH) neuron-glia remodeling. Molecular and Cellular Endocrinology (impact factor: 3.69) 348(1): 95-103. Jyoti Parkash ([email protected]) 5 (13) Jyoti Parkash, Irene Cimino, Nicoletta Ferraris, Susan Wray, Vincent Prevot, Paolo Giacobini 2012: Suppression of β1- integrin in gonadotropin-releasing hormone cells distrupts migration and axonal extension resulting in severe reproductive alterations. Journal of Neuroscience (impact factor: 7.93) 32(47):16992-17002. (14) Naresh Kumar Hanchate, Paolo Giacobini, Pierre Lhuillier, Jyoti Parkash, Cécile Espy, Corinne Fouveaut, Chrystel Leroy, Stéphanie Baron, Céline Campagne, Francis Collier, Alfons GarciaPineiro, Didier Dewailly, Christine Cortet-Rudelli, Ksenija Gersak, Michel Pugeat, Jacques Young, Jean-Pierre Hardelin, Vincent Prevot and Catherine Dodé 2012: SEMA3A, a Gene Involved in Axonal Pathfinding, Is Mutated in Patients with Kallmann Syndrome PLoS Genetics (impact factor: 9.13) 8(8):e1002896. (15) Celine Campagne, Paolo Giacobini, Jyoti Parkash (Equally contributed), Naresh Kumar Hanchantae, Daniel Mazure, Vincent Prevot 2012: Neuronal NOS Neurons Obligatory for Kisspeptin Induced preovulatory LH surge (Communicated in Nature Neuroscience). (16) Nicole Bellefontaine, Jyoti Parkash, Charlotte Vanacker, William Colledge, Xavier d'Anglemont de Tassigny, Sebastien Bouret Vincent Prevot 2012: Leptin facilitates reproduction through neuronal nitric oxide signaling in the hypothalamic preoptic region in mice. (Communicated in Journal of Clinical investigation). (17) Jyoti Parkash, Anne Loyens, Sarah Gallet, Eglantine Balland, François Pralong, Jeroen Pasterkamp, Vincent Prevot, Paolo Giacobini 2013: Semaphorin 7A expression in tanycytes is regulated by sex-steroid hormones and controls gonadotropin-releasing hormone-1 (GnRH-1) cell plasticity (Under prep. For Cell). Presentations in Conferences National 1. Sema7A is a Tanycytic-Secreted Guidance Cue Regulates GnRH Axon Plasticity in adult Brain. 30th Annual meeting of Indian Academy of Neurosciences. 27th-30th Oct. 2012 Amritsar India. 2. Interactive effect of excitotoxic injury and dietary restriction on neurogenesis and neurotrophic factors in adult male rat brain; International symposium on “Molecular Aspects of Brain Aging and Neurological Disorders” at Department of Biotechnology, Guru Nanak Dev University Amritsar from 28th - 29th November, 2008. 3. Neuronal glial interactions are involved in the control of GnRH neurosecretion in the hypothalamus of adult cycling female rats; XXIV Annual conference of Indian Academy of Neuroscience, ITRC Lucknow from 17th - 20th December (Annals of Neuroscience; 97 (13), 2006). 4. Polysialylated form of neural cells adhesion molecule mediated neuroplasticity within GnRH neurons in female rats; XXII annual meeting from 28th - 30th January, Gwalior, India (Annals of Neuroscience 94 (2): 253, 2005). International 1. Semaphorin 7A expression in tanycytes is regulated by sex-steroid hormones and controls gonadotropinreleasing hormone-1 (GnRH-1) cell plasticity. SFN, November 12 - 16, 2011, in Washington DC. No. 2011-S-2816-SfN. Jyoti Parkash ([email protected]) 6 2. Nitric oxide neurons in the preoptic area of the hypothalamus are a direct target of leptin: implications for the reproductive axis. SFN, November 12 - 16, 2011, in Washington DC. No. 2011-S-12579-SfN. 3. Sema7A is a Tanycytic-Secreted Guidance Molecule and Regulates GnRH Axon Outgrowth in the Adult Brain; 14th Neuroscience meeting on 29th October, 2010 Lille. 4. Phosphorylation of N-methyl-D-aspartic acid receptor-associated neuronal nitric oxide synthase modulates hypothalamic nitric oxide production: The role of estrogen during ovarian cycle in female rats; 7th international congress of Neuroendocrinology from 7th - 11th July, Rouen, France (Journal of Neuroendocrinology P2-182, 2010). 5. Phosphorylation of N-methyl-D-aspartic acid receptor-associated neuronal nitric oxide synthase modulates hypothalamic nitric oxide production: The role of estrogen during ovarian cycle in female rats; 36th Colloque De la societie de neuroendocrinologie international congress from 15th - 18th September, 2009, Nice, France. 6. Potential of PSA-NCAM to Mediate Neuronal-glial interaction in GnRH Neurosecretion: Role of GABAergic and noradrenergic neurotransmitters; 29th Annual Japan Neuroscience Society (JNS) Kyoto from 19th - 21st July (Neuroscience Research, 2006). 7. Activity dependent neuronal-glial remodeling in the ME of adult rat hypothalamus: Role of GABAergic and noradrenergic neurotransmitters; 7th Biennial Asian Pacific Society for Neurochemistry (APSN 2006) Singapore from 2nd - 5th July (Journal of Neurochemistry 98 (1): 71, 2006). 8. PSA-NCAM mediated neuronal plasticity in the hypothalamus of adult brain; ISN-ESN Biennial meeting, Austria from 21st - 26th August (Journal of Neurochemistry, 2005). Personal Details Date of birth 1st September 1979 Sex Male Marital Status Married State Himachal Pradesh District Hamirpur Nationality Indian Languages known Hindi, Punjabi and English Phone +91-1972243036 (Home) +33-751048184 (France) References: Dr. Vincent PREVOT (Director) Development and Plasticity of Postnatal Brain Jean-Pierre Aubert Research Center Jyoti Parkash ([email protected]) 7 INSERM U837, team1, place de Verdun 59045 Lille cedex France Tel:+33-320622064 E-mail : [email protected] Dr. Paolo Giacobini (Assistant Professor) Inserm Unit 837 Jean-Pierre Aubert Research Centre Team 2 Development and plasticity of the postnatal brain NEUROBESE International Associated Laboratory Place de Verdun 59045 Lille Cedex - France E-mail : [email protected] Dr. Gurcharan Kaur (Professor and Head) Neurochemistry and Neuroendocrology Lab. Department of Biotechnology Guru Nanak Dev University Amritsar- 143 005, Punjab, India Phone: +91-183-2258809 Ext. 3176 (Off.) Email: [email protected] Research Summary / Projects worked on (past and present): 1. Sema7A is an tanycytic Chemotropic Factor that Controls GnRH Axon Plasticity in the Adult Brain Semaphorins constitute one of the largest protein families of phylogenetically conserved guidance cues. In this work, we have focused our attention on Semaphorin 7A (Sema7A) whose function has been studied most extensively in the context of immune-cell function and cancer cell biology, and only few reports address the neuronal role of this semaphorin. Recently, prominent expression of Sema7A has been documented in different areas of the nervous system characterized by persisting structural plasticity. Interestingly, Sema7A transcript has been also documented in the adult median eminence, where the nerve terminals of Gonadotropin Hormone-Releasing Hormone (GnRH) neurons are located and secrete the hormone in the pituitary portal capillary system. Here we showed for the first time that Sema7A protein expression in the adult female rats is hormonally regulated and that its expression is increased in the diestrus phase of the estrous cycle, corresponding to a physiological reduction in GnRH secretion. We also demonstrated that the rise in progesterone levels occurring during diestrus is responsible for the upregulation of Sema7A expression. Western blot analysis was also performed on purified tanycyte cultures isolated from embryonic median eminences and indicated that Sema7A is indeed produced by these cells and acts on GnRH-1 axons terminals, which express 1-integrin, one the known Sema7A receptors. Finally, in vitro functional experiments performed on immortalized GnRH cell lines highlighted a role of Sema7A being an inhibitory signal for GnRH axonal elongation. Taken together these results show a hitherto unidentified role for Sema7A and 1-integrin signaling in mediating periodical GnRH axon remodeling in Jyoti Parkash ([email protected]) 8 the median eminence of the adult hypothalamus. These data identify a previously unknown function for Sema 7A signalling in inducing adult central nervous system axon retraction, and raise the possibility that tanycytic cells may actively participate in synaptic plasticity in specific functional domains of the adult brain. (Post doctoral, Current) 2. Paracrine and Juxtacrine basis for Neuronal Plasticity The aim of our study to find juxtacrine and paracrine basis of neuronal plasticity in adult brain. Although it is now clear that glia-to neuron communication systems are important components of the central neuroendocrine process controlling mammalian reproduction, the precise mechanisms by which morphological changes are promoted at the median eminence, which is the termination field of those neurons secreting gonadotropin releasing hormone (GnRH) and the communications pathways that specifically link glia and neuron remodeling await further elucidation. This neuronal and glial remodeling is reversed upon cessation of stimulation. Such an activity-dependent structural plasticity illustrates, therefore, both a network and cellular adaptation to increased hormone demand and offers a striking example that dynamic changes in the morphology of adult neurons and glial are intimately related to normal neuronal function. The ongoing study in this project was aimed to determine whether juxtacrine (PSA-NCAM) and/or paracrine (erbB signaling) communication processes and the crosstalk between these two modes of signalization might play a major role in the integration of the great diversity of stimuli that astrocytes, tanycytes and GnRH axons receive under varying physiological situations during estrous cycle within the median eminence of the hypothalamus. (Post doctoral) 3. Matrix Metalloproteinases are expressed in the median eminence of the hypothalamus and their activities vary during the rat estrous cycle Matrix metalloproteinases (MMPs) -Zn2+dependent endopeptidases that cleave protein components of the extracellular matrix- are prominently expressed during reproductive processes such as menstruation, ovulation, uterine implantation, parturition, postpartum uterine involution, etc. However whether they are also involved in processes used by the neuroendocrine brain to control female reproductive function is not known. The aim of this work was to determine whether MMPs are expressed in the ME of the hypothalamus and whether their expression and/or activity varies during the estrous cycle. Our results show that metalloproteinase activities are expressed in the ME. Gelatinase activities are detected in the external zone of the ME at the proximity of GnRH nerve terminals. Interestingly, our result suggest that these activities vary during the estrous cycle and reach a maximum on the afternoon of proestrus, when the preovulatory surge of GnRH occurs. (Post doctoral) 4. Role of Glutamate neurotransmitter and D-Serine Gliotransmitter on GnRH regulation in relation to NO Activation of NMDARs by glutamate in endothelial cell activates eNOS which results more generation of NO selectively stimulate GnRH release in ME. Endothelial cells can indeed sense peripheral information like estradiol and provide feedback mechanism through NO release and co-ordinating the activity of neurons, astroglia and endothelium in specific neurovascular zone of CNS. Endothelial signaling coordinate the activity of neuroglia at the neuroendocrine synapse to deliver functionally meaningful episodes of GnRH secretion. This will be first report that endothelial cells have NMDARs and D serine syntheisze by tanycytes and have role in neuroendocrine regulation. (Post doctoral). Jyoti Parkash ([email protected]) 9 5. Allopregnanolone Prevents Dieldrin-induced NMDA Receptor Internalization and Neurotoxicity in Cortical Neurons by Preserving GABAA Receptor Functionality Dieldrin is an organochlorine pesticide that accumulates in the adipose tissue and brain of mammals. It has convulsant activity due to its antagonism of the γ-aminobutiric acid A receptor (GABAAR). We have previously reported that long-term exposure to dieldrin causes the internalization of N-methyl-D-aspartate receptor (NMDAR) as a result of persistent GABAAR inhibition. Because the neuroesteroids 17β-estradiol (E2) and allopregnanolone (AP) are known to modulate the traffiking of GABA AR and NMDAR at the cell membrane, our goal was to study the effects of E2 and AP against dieldrin-induced NMDAR internalization and neuronal death in cultured cortical neurons. We found that long-term exposure to 60 nM dieldrin caused the internalization of the NMDAR subunits NR1 and NR2B, but not NR2A. Treatment with either E2 or AP prevented dieldrin-induced reduction of NR1 and NR2B on the cell membrane. Furthermore, prolonged exposure to 200 nM dieldrin down-regulated the expression of NR2A; however, this effect was only inhibited by AP. In addition, we show that postsynaptic density 95 (PSD95) has physical association with NR2A-containing NMDARs, whereas synapse-associated protein 102 (SAP102) immunoprecipitated with NR2B-containing NMDARs in our neuronal cultures. Moreover, these associations were reduced after longterm exposure to dieldrin. Although both hormones restored NMDAR function, as measured by NMDAinduced intracellular calcium concentration rise, AP (but not E2) was neuroprotective against dieldrininduced neuronal death. The results suggest that AP may protect cortical neurons against the neurotoxicity caused by long-term exposure to dieldrin by maintaining GABAAR and NMDAR functionalities. (Post doctoral). 6. Sema3A is an Endothelial-Secreted Chemotropic Factor that Controls GnRH Axon Plasticity in the Adult Brain Neuropilin-1 (Npn-1) guides the development of the nervous and vascular systems. Here we show that Sema3A, the ligand of Npn-1, is expressed by adult vascular endothelial cells in response to the ovarian cycle and promotes the sprouting of axons containing gonadotropin-releasing hormone (GnRH) (the neuropeptide controlling reproduction) at the neuroendocrine synapse in the median eminence of the hypothalamus. Antibodies that bind to Sema-binding domain of Npn-1 prevent both Sema3A and ovarian cycle-mediated effects on GnRH axon plasticity in situ. Local in vivo infusion of anti-Npn-1 disrupted the ovarian cycle, which requires a pulsatile, coordinated delivery of GnRH into the hypothalamo-hypophyseal portal system. These data identify a previously unknown function for Sema3A/Npn-1 signalling in inducing adult central nervous system axon growth, and raise the possibility that endothelial cells may actively participate in synaptic plasticity in specific functional domains of the adult brain. (Post doctoral). Jyoti Parkash ([email protected])