Zhengui Xia, PhD, MS
- Department of Pharmacology
- Graduate Program in Neurobiology and Behavior
- Graduate Program in Molecular and Cell Biology
- Institute for Stem Cell and Regenerative Medicine (ISCRM)
- Mechanisms of neurogenesis
- KEYWORDS: Apoptosis, Neurogenesis, Adult neurogenesis, Children's health, Developmental toxicology, Genetic susceptibility to toxins, Nervous system toxicity, Neurotoxicology, Neurobiology, olfaction and cognition, heavy metals, lead, cadmium, gene-environment interactions, GXE, Alzheimer’s disease, cognitive decline, senile dementia; sex differences on disease susceptibility, window of susceptibility.
In the News
One of our research interests is to elucidate signal transduction mechanisms that regulate the fate of neural stem cells, i.e. what makes a neural stem cell proliferate and differentiate into neurons or glia in the mammalian brain. We are interested in neural stem cell regulation both during embryonic development and in adult brain (adult neurogenesis). Specifically, recent studies in our lab suggest a novel role for the extracellular-signal-regulated kinase 5 (ERK5) MAP kinase in regulating these processes. The elucidation of molecular mechanisms that regulate neural progenitor cell proliferation and differentiation is important for an understanding of neural developmental and neurodegenerative diseases. Furthermore, stem cell-based cell replacement therapy offers enormous potential for the treatment of a variety of developmental, psychiatric, neurodegenerative and aging related diseases for which there are currently no cures. Moreover, environmental toxicants may cause neurotoxicity both in the development and in adult brain by perturbing these signaling mechanisms that regulate neurogenesis.
II. Role of a gene and environment interaction on lead-induced cognitive impairment and Alzheimer’s disease risks.
Lead is a heavy metal of great public health concern in the US and globally. In addition to its well-characterized developmental neurotoxicity, cumulative lead exposure is also neurotoxic to adults and can lead to accelerated, persistent cognitive decline in adult humans. The hippocampus is a region of the brain critical for learning and memory, especially spatial learning. Adult hippocampal neurogenesis is the process whereby adult neural stem cells in the dentate gyrus of the hippocampus leads to the generation and functional integration of adult-born neurons in the hippocampus. These adult-born neurons can influence hippocampus-dependent learning and memory. Although adult neurogenesis is modulated by various extracellular stimuli, by the environment, and by neurotoxicants including lead and ethanol, there is a paucity of information regarding the effect of gene-environment interactions (GxE) on adult neurogenesis. Our current research focuses on the effect of lead-genetic background interactions on adult neurogenesis and hippocampus-dependent learning and memory.
III. Cadmium neurotoxicity
Cadmium (Cd) is a heavy metal of high interest to the Superfund Initiative. It has no known physiological function but is a neurotoxicant. Cd exposure is associated with cognitive and olfactory impairment in humans. However, little is known concerning the underlying molecular and cellular mechanisms. We are currently exploring the molecular and cellular basis for the deleterious effects of Cd on olfaction and cognition in mouse models, with a focus on its effects on adult neurogenesis and Ca2+signaling critical for hippocampus-dependent memory. We hypothesize that Cd interferes with adult neurogenesis in the dentate gyrus of the hippocampus and in olfactory bulb, and disrupts Ca2+signaling in neurons. We further hypothesize that these adverse cellular and molecular effects may underlie Cd neurotoxicity in cognition and olfaction. We are testing these hypotheses both in primary cultured neural stem cells and in vivo in mice.
A. Refereed Research Articles
It is customary in Toxicology, Neurobiology and Signal Transduction Biology for students and postdoctoral fellows to be listed as the first author while the PI is indicated as the senior author by assuming the last position on journal publications. Those articles in which I am the senior author as PI are marked by **.
1. Xia Z, Zhu R, Cao X, and Zou G. (1987) Purification and characterization of restriction endonuclease Bsp 78I. Acta Biochim. Biophys. Sinica (Chinese). 19: 27-34.
2. Tota MR, Xia Z, Storm DR, and Schimerlik MI. (1990): Reconstitution of Muscarinic Receptor Mediated Inhibition of Adenylyl Cyclase. Mol. Pharmacol. 37: 950-957. PMID: 2113606
3. Xia Z and Storm DR (1990): A-Type ATP Binding Consensus Sequence is Critical for the Catalytic Activity of the Calmodulin Sensitive Adenylate Cyclase from Bacillus anthracis. J. Biol. Chem. 265: 6517-6520. PMCID: 2108958
4. Xia Z, Refsdal CDR, Merchant KM, Dorsa DM, and Storm DR. (1991) Distinct Patterns for the Distribution of mRNA for the Calmodulin-Sensitive Adenylate Cyclase in Rat Brain: Expression in Areas Associated with Learning and Memory. Neuron 6: 431-443. PMID: 2113606
5. Choi EJ, Xia Z, and Storm DR. (1992) Stimulation of the Type III Olfactory Adenylyl Cyclase by Calcium and Calmodulin. Biochem. 31: 6492-6498. PMID: 1633161
6. Xia Z, Choi EJ, Wang F, and Storm DR. (1992) The Type III Calcium/Calmodulin Sensitive Adenylyl Cyclase is not Specific to Olfactory Sensory Neurons. Neurosci. Lett. 144: 169-173. PMID: 1436697
7. Xia Z, Choi EJ, Wang F, Blazynski C, and Storm DR. (1993) The Type I Calmodulin Sensitive Adenylyl Cyclase Is Neural Specific. J. Neurochem. 60: 305 311. PMID: 8417150
8. Villacres EC, Xia Z, Bookbinder LH, Edelhoff S. Adler DA, Disteche CM, and Storm DR. (1993) Cloning, Chromosomal Mapping, and Expression of Human Fetal Brain Type I Adenylyl Cyclase. Genomics 16: 473-478. PMID: 8314585
9. Wu Z, Thomas SA, Xia Z, Villacres EC, Palmiter RD, and Storm DR. (1995) Deficient Spatial Memory and Altered LTP in Type I Adenylyl Cyclase Mutant Mice. Proc. Natl. Acad. Sci. USA 92:220-224. PMID: 7816821; PMCID: PMC42849
10. Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME. (1995) Opposing Effects of ERK and JNK-p38 MAP Kinases on Apoptosis. Science (Research Article) 270:1326-1331. PMID: 7481820
Note: Reference #10 was recently selected as a highly cited paper in the field of Biology & Biochemistry by ISI Essential Science Indicators (ESI). According to the ISI Essential Science Indicators Web product, this paper was ranked at #9 among Clinical Medicine papers published in the past decade as of June 2004. (http://www.incites.com/papers/DrZhenguiXia.html), and has been cited > 5149 times as of July 17, 2014.
11. Xia Z, Dudek H, Miranti CK, Greenberg ME. (1996) Calcium Influx via the NMDA Receptor Induces Immediate Early Gene Transcription by a MAP Kinase/ERK Dependent Mechanism. J. Neurosci. 16(17): 5425-5436. PMID: 8757255
12. Dickens M, Rogers J, Cavanagh J, Raitano A, Xia Z, Halpern JR, Greenberg, ME, Sawyers CL, Davis J. (1997) A cytoplasmic inhibitor of the JNK signal transduction pathway. Science 277: 693-696. PMID: 9235893
13. Xing J, Kornhauser JM, Xia Z, Thiele EA, and Greenberg ME. (1998) Nerve growth factor activates extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways to stimulate CREB serine 133 phosphorylation. Mol. Cell. Biol. 18(4): 1946-1955. PMID: 9528766; PMCID: PMC121424
14. Yue TL, Niá J, Romanic AM, Gu JL, Keller P, Wang C, Kumar S, Yuá GL, HartÜ TK, Wang X, Xia Z, DeWolf Jr DE and Feuerstein GE (1999) TL1, a Novel TNF-like Cytokine, Induces Apoptosis in Endothelial Cells: Involvement of Activation of Stress Protein Kinases (stress-activated protein kinase and p38 mitogen-activated protein kinase) and Caspase-3 Like Protease . J. Biol. Chem. 274:1479-1486. PMID: 9880523
**15. Hetman M, Kanning K, Smith-Cavanaugh JE, and Xia, Z. (1999) Neuroprotection by Brain-Derived Neurotrophic Factor Is Mediated by Extracellular-Signal-Regulated Kinase and Phosphatidylinositol-3 Kinase. J. Biol. Chem. 274: 22569-22580. PMID: 10428835
**16. Hetman M, Smith-Cavanaugh JE, Kimelman D and Xia Z, (2000) Role of Glycogen Synthase Kinase-3β in Neuronal Apoptosis Induced by Trophic Withdrawal. J. Neurosci. 20(7):2567-2574. PMID: 10729337
**17. Namgung U. and Xia Z. (2000) Arsenite-Induced Apoptosis in Cortical Neurons Is Mediated by c-Jun N-Terminal Protein Kinase 3 and p38 Mitogen-Activated Protein Kinase. J. Neurosci. 20(17): 6442-6451. PMID: 10964950
18. Ghatan S, Larner S, Kinoshita Y, Hetman M, Patel L, Xia Z, Youle RJ, Morrison RS. (2000) p38 Mitogen activated protein kinase mediates Bax translocation and caspase induction in nitric oxide-induced apoptosis in neurons. J. Cell Biol. 150 (2): 335-347. PMID: 10908576; PMCID: PMC2180235
19. Poser S, Impey K, Trinh K, Xia Z, and Storm DR. (2000) SRF-dependent gene expression is required for mitogen-induced proliferation through a PI3 kinase signal transduction cascade. EMBO J. 19 (18): 4955-4966. PMID: 10990459; PMCID: PMC314219
20. Wong ST, Trinh K, Wei J, Lowe G, Gaggar A, Xia Z, Gold GH and Storm DR. (2000) Disruption of the Type III Adenylyl Cyclase Gene Leads to Peripheral and Behavioral Anosmia in Transgenic Mice. Neuron 27: 487-497. PMID 11055432
**21. Cavanaugh JE, Ham J, Hetman M, Poser S, Yan C, and Xia Z. (2001) Differential Regulation of Mitogen Activated Protein Kinases ERK1/2 and ERK5 by Neurotrophins, Neuronal Activity and cAMP in Neurons. J. Neurosci. 21(2): 434-443. PMID: 11160424
**22. Figueroa Masot XA, Hetman M, Higgins M, Kokot N, Xia Z (2001) Differential Role of Bcl-2 Phosphorylation in Paclitaxel (Taxol)-Induced Apoptosis in Post-Mitotic Neurons and Proliferating HEK 293 Cells. J. Neurosci. 21(13):4657-67. PMID: 11425893
**23. Namgung U, and Xia Z. (2001) Arsenic induces apoptosis in rat cerebellar neurons which requires activation of JNK 3 and p38 MAP kinases. Toxicol. Appl. Pharmacol. 174(2): 130-8. PMID: 11446828
24.Chan GCK, Lernmark U, Xia Z, and Storm DR. (2001) DNA Elements of the Type I Adenylyl Cyclase Gene Locus Enhance Reporter Gene Expression in Neurons and Pinealocytes. Eur. J. Neurosci. 13 (11), 2054-2066. PMID: 11422446
25. Mabuchi T, Kitagawa K, Kuwabara K, Takasawa K, Ohtsuki T, Xia Z, Storm D, Yanagihara T, Hori M, Matsumoto M. (2001) Phopshorylation of cAMP response element-binding protein in hippocampal neurons as a protective response after exposure to glutamate in vitro and ischemia in vivo. J. Neurosci. 21:9204-13. PMID: 11717354
26. Kornhauser JM, Cowan CW, Shaywitz AJ, Dolmetsch RE, Griffith EC, Hu LS, Haddad C, Xia Z, Greenberg ME. (2002) CREB transcriptional activity in neurons is regulated by multiple, calcium-specific phosphorylation events. Neuron 34: 221-233. PMID: 11970864
27. Zhu Y, Mao XO, Sun Y, Xia Z, Greenberg DA. (2002) p38 Mitogen-activated Protein Kinase Mediates Hypoxic Regulation of Mdm2 and p53 in Neurons. J. Biol. Chem. 277(25):22909-14. PMID: 11948180
28. Ghahremani MH, Keramaris E, Shree T, Xia Z, Davis RJ, Flavell R, Slack RS, Park DS. (2002). Interaction of the c-Jun/JNK pathway and cyclin-dependent kinases in death of embryonic cortical neurons evoked by DNA damage. J. Biol. Chem. 277(38):35586-96. PMID: 12091388
**29. Hetman M, Hsuan SL, Habas A, Higgins MJ, Xia Z. (2002) ERK1/2 Antagonizes Glycogen Synthase Kinase-3beta -induced Apoptosis in Cortical Neurons. J. Biol. Chem. 277(51):49577-49584. PMID: 12393899
30. Poser S, Impey S, Xia Z, and Storm DR. (2003) Brain-derived neurotrophic factor protection of cortical neurons from serum withdrawal-induced apoptosis is inhibited by cAMP. (2003) J. Neurosci. 23(11):4420-7. PMID: 12805282
**31. Caughlan A, Newhouse K, Namgung U, and Xia Z. (2004) Chlorpyrifos Induces Apoptosis In Rat Cortical Neurons That Is Regulated By A Balance Between p38 And ERK/JNK MAP Kinases. Tox. Sci. 78(1): 125-34. PMID: 14691213
**32. Liu L, Cavanaugh JE, WangY, Sakagami H, Mao Z, and Xia Z. (2003) ERK5 Activation of MEF2-Mediated Gene Expression Plays A Critical Role In BDNF-Promoted Survival of Developing But Not Mature Cortical Neurons. Proc. Natl. Acad. Sci. USA 100(14): 8532-8537. (PMCID: PMC166263)
**33. Namgung U, Kim DH, Lim SR, Xia Z (2003) Blockade of calcium entry accelerates arsenite-mediated apoptosis in rat cerebellar granule cells. Molecules and Cells 15: 256. PMID: 12803490
** 34. Newhouse K, Hsuan SH, Chang SH, Cai C, Wang Y, and Xia Z (2004). Rotenone-Induced Apoptosis Is Mediated By p38 And JNK MAP Kinases In Human Dopaminergic SH-SY5Y Cells. Tox. Sci. 79: 137-146. PMID: 14976342
**35. Chang SH, Poser P, and Xia Z (2004). A Novel Role For Serum Response Factor In Neuronal Survival . J. Neurosci. 24 (9): 2277-85. PMID: 14999078
36. Tang X, Wang X, Gong X, Tong M, Park D, Xia Z, Mao Z. Cyclin-dependent kinase 5 mediates neurotoxin-induced degradation of the transcription factor myocyte enhancer factor 2. J. Neurosci. 2005: 25(19):4823-3. PMID: 15888658
**37. Hsuan SH, Klintworth HM, and Xia Z. (2006) Basic Fibroblast Growth Factor Protects Dopaminergic Cells against Rotenone Toxicity through activation of the Extracellular-Signal-Regulated Kinases 1/2 and Phosphatidylinositol-3 Kinase. J. Neurosci. 26:4481-91. PMID: 16641227
**38. Liu L, Cundiff P, Abel GM, Wang Y, Faigle R, Sakagami H, Xu M, Xia Z (2006) Extracellular Signal-Regulated Kinase (ERK) 5 Is Necessary and Sufficient to Specify Cortical Neuronal Fate. Proc. Natl. Acad. Sci. USA. 103(25):9697-702. Epub 2006 Jun 9. (PMCID: PMC1480469)
**39. Cai B, Becker EBE, Bonni A, and Xia Z. (2006) p38 MAP Kinase Mediates Apoptosis Through Phosphorylation of BimEL At Ser65. J. Biol. Chem. 281(35):25215-22. Epub 2006 Jul 3. PMID: 16818494 [PubMed - indexed for MEDLINE]
**40. Wang Y, Su B, and Xia Z. (2006) BDNF Activates ERK5 In Cortical Neurons via a Rap1-MEKK2 Signaling Cascade J. Biol. Chem. 281 (47): 35965-74. Epub 2006 Sept 25. (PMID: 17003042) [PubMed - indexed for MEDLINE]
**41. Cude K, Wang Y, Choi HJ, Hsuan SL, Zhang HL, Wang CY, and Xia Z. (2007) Regulation of the G2/M Cell Cycle Progression by the ERK5-NFκB Signaling Pathway. J. Cell Biol. 177 (2): 253-64. (PMCID: PMC2064134)
Note: This paper was highlighted as one of the key papers appearing in that issue of the journal and is discussed in a section called “In This Issue”.
**42. Klintworth H, Newhouse K, Li TT, Faigle R, Choi WS, Xia Z. (2007) Activation of c-Jun N-terminal Protein Kinase is a Common Mechanism Underlying Paraquat- and Rotenone-Induced Dopaminergic Cell Death. Tox. Sci. 97(1): 149-62. (PMID: 17324951 [PubMed - indexed for MEDLINE] ).
**43. Wang Y, Liu L, and Xia Z (2007). BDNF stimulates the transcriptional and neuroprotective activity of myocyte-enhancer factor 2C through an ERK1/2-RSK2 signaling cascade. J. Neurochem. 102(3): 957-66. (PMID: 17630987 [PubMed - indexed for MEDLINE] )
**44. Faigle R, Liu L, Funa K, and Xia Z (2008) Opposing effects of retinoid signaling on astroglial differentiation in progenitor cells derived from Embryonic day 13 and day 17 cortex. J. Neurochem. 106(4): 1681-98. (PMCID: PMC2581522)
**45. Cai B and Xia Z. (2008) p38 MAP Kinase Mediates Arsenite-Induced Apoptosis through FOXO3a Activation and Induction of Bim Transcription. Apoptosis: 13:803–810. (PMCID: PMC2442769)
**46. Choi WS, Kruse SE, Palmiter RD, and Xia Z. (2008) Mitochondrial complex I inhibition is not required for dopaminergic neuron death induced by rotenone, MPP+, or paraquat. PNAS USA: 105: 15136-41. (PMCID: PMC2567505).
**47. Cundiff P, Liu L, Wang Y, Zou J, Pan Y, Abel G, Duan X, Ming G, Englund C, Hevner R, Xia Z. (2009) ERK5 MAP Kinase Regulates Neurogenin1 During Cortical Neurogenesis. PLoS One: 4(4):e5204. Epub 2009 Apr 13. (PMCID: PMC2664926).
**48. Klintworth H, Garden G, Xia Z. (2009) Rotenone and Paraquat do not Directly Activate Microglia or Induce Inflammatory Cytokine Release. Neurosci. Lett: 462: 1-5 (PMCID: PMC2796146).
49. Wang Z, Li V, Chan GC, Phan T, Nudelman AS, Xia Z and Storm DR (2009) Adult Type 3 Adenylyl Cyclase Deficient Mice are Obese. PLoS ONE: 4: e6979. (PMCID: PMC2735775).
**50. Choi WS, Abel G, Klintworth H, Flavell R. and Xia Z. (2010) JNK3 Mediates Paraquat- and Rotenone-Induced Dopaminergic Neuron Death. J. Neuropathol. Exp. Neurol.: 69(5):511-20. (PMCID: PMC3061491)
**51. Choi WS, Palmiter RD, and Xia Z. (2011) Loss of mitochondrial complex I activity potentiates dopamine neuron death induced by microtubule dysfunction in a Parkinson's disease model. J. Cell Biol. 192: (5): 873-882 (PMCID: PMC3051820)
Note: This paper was highlighted as one of the key papers appearing in that issue of the journal and is discussed in a section called “In Focus”, by Ben Short, The wrong suspect? (2011) J. Cell Biol. 192: (5): 707.
**52. Zou J, Pan YW, Wang Z, Chang SH, Wang WB, Wang X, Tournier C,, Storm DR, and Xia Z (2012) Targeted Deletion of ERK5 MAP Kinase in the Developing Nervous System Impairs Development of GABAergic Interneurons in the Main Olfactory Bulb and Behavioral Discrimination between Structurally Similar Odorants. J. Neurosci. 32 (12):4118-4132. PMID: 22442076; PMCID: PMC3333842
**53. Pan YW, Zou J, Wang W, Sakagami H, Garelick MG, Abel G, Kuo CT, Storm DR, Xia Z. (2012) Inducible and conditional deletion of extracellular signal-regulated kinase 5 disrupts adult hippocampal neurogenesis. J Biol Chem. 2012 Jul 6;287(28):23306-17. Epub 2012 May 29. PMCID: PMC3390609
**54. Pan YW, Chan GCK, Kuo CT, Storm DR, and Xia Z. (2012) Inhibition of Adult Neurogenesis by Inducible and Targeted Deletion of ERK5 Mitogen-Activated Protein Kinase Specifically in Adult Neurogenic Regions Impairs Contextual Fear Extinction and Remote Fear Memory. J. Neurosci. 32 (19): 6444-6455. PMID: 22573667 PMC3363363
55. Chen XM, Xia Z, and Storm DR (2012) Stimulation of Electro-Olfactogram Responses in the Main Olfactory Epithelia by Airflow Depend on the Type 3 Adenylyl Cyclase. J. Neurosci. 32: 15769-15778. PMID: 23136416 PMCID: PMC3506261
**56. Pan YW, Kuo CT, Storm DR, Xia Z. (2012) Inducible and Targeted Deletion of the ERK5 MAP Kinase in Adult Neurogenic Regions Impairs Adult Neurogenesis in the Olfactory Bulb and Several Forms of Olfactory Behavior. PLoS ONE. 7(11):e49622. doi: 10.1371/journal.pone.0049622. PMID: 23185386; PMC3504159
**57. Pan YW, Storm DR, Xia Z. (2012) The Maintenance of Established Remote Contextual Fear Memory Requires ERK5 MAP Kinase and Ongoing Adult Neurogenesis in the Hippocampus. PLoS One. 7(11):e50455. PMID: 23189204; PMC3506604
**58. Wang W, Pan YW, Wietecha T, Zou J, Abel GM, Kuo CT, Xia Z. (2013) Extracellular Signal-regulated Kinase 5 (ERK5) Mediates Prolactin-stimulated Adult Neurogenesis in the Subventricular Zone and Olfactory Bulb. J Biol Chem. 288(4):2623-31. PMID: 23223235; PMC3554929
**59. Li T, Pan YW, Wang W, Abel G, Zou J, Xu L, Storm DR, Xia Z. (2013) Targeted Deletion of the ERK5 MAP Kinase Impairs Neuronal Differentiation, Migration, and Survival During Adult Neurogenesis in the Olfactory Bulb. PLoS One 8(4):e61948. PMID: 23630619; PMC3632513.
**60. Li T, Wang W, Pan YW, Xu L, Xia Z. (2013) A Hydroxylated Metabolite of Flame-Retardant PBDE-47 Decreases the Survival, Proliferation and Neuronal Differentiation of Primary Cultured Adult Neural Stem Cells and Interferes With Signaling of ERK5 MAP Kinase and Neurotrophin 3. Tox Sci. 134(1):111-24. PMID: 23564643; PMC3693129
** 61. Zou J, Storm DR, Xia Z. (2013) Conditional Deletion of ERK5 MAP Kinase in the Nervous System Impairs Pheromone Information Processing and Pheromone-Evoked Behaviors. PLoS One. 8(10):e76901. PMID: 24130808; PMC3793934
**62. Wang W, Pan YW, Zou J, Li T, Abel GM, Palmiter RS, Storm DR, and Xia Z. (2014) Genetic Activation of ERK5 MAP Kinase Enhances Adult Neurogenesis and Extends Hippocampus-dependent Long-term Memory. J. Neurosci. 34(6):2130-47. PMID: 24501354; PMC3913867
**63. Choi WS and Xia Z (2014) Maneb-induced dopaminergic neuronal death is not affected by loss of mitochondrial complex I activity: Results from primary mesencephalic dopaminergic neurons cultured from individual Ndufs4+/+ and Ndufs4-/- mouse embryos. NeuroReport. Neuroreport. 2014 Dec 3;25(17):1350-5. PMID: 25275677; PMC4213303
**64. Choi WS, Kim HW, Xia Z. (2015) JNK inhibition of VMAT2 contributes to rotenone-induced oxidative stress and dopamine neuron death. Toxicology. 2015 Feb 3;328:75-81. doi: 10.1016/j.tox.2014.12.005. Epub 2014 Dec 9. PMID: 25496994; PMC4308505
65. Yu AK, Song L, Murray KD, van der List D, Sun C, Shen Y, Xia Z, Cortopassi GA. (2015) Mitochondrial complex I deficiency leads to inflammation and retinal ganglion cell death in the Ndufs4 mouse. Hum Mol Genet. 2015 Feb 4. pii: ddv045. [Epub ahead of print]
66. Luo J, Chen, X, Pan, YW, Lu. S, Xia, Z and Storm, DR (2015) The Type 3 adenylyl cyclase is required for the survival and maturation of newly generated granule cells in the olfactory bulb. PLoS One. Mar 25;10(3):e0122057. PMID: 25807252
**67. Wang W, Lu S, Li T, Pan YW, Zou J, Abel GM, Xu L, Storm DR, Xia Z. (2015) Inducible Activation of ERK5 MAP Kinase Enhances Adult Neurogenesis in the Olfactory Bulb and Improves Olfactory Function. J. Neurosci. 35(20):7833-49. PMID: 25995470
**68. Zou J, Wang W, Pan YW, Abel GM, Storm DR, and Xia Z. (2015) Conditional Inhibition of Adult Neurogenesis by Inducible and Targeted Deletion of ERK5 MAP Kinase is Not Associated with Anxiety/Depression-like Behaviors. eNeuro. 2015 Apr 16;2(2). pii: ENEURO.0014-14.2015. doi: 10.1523/ENEURO.0014-14.2015. eCollection 2015 Mar-Apr.
**69. Engstrom A, Wang H, Xia Z (2015) Lead decreases cell survival, proliferation, and neuronal differentiation of primary cultured adult neural precursor cells through activation of the JNK and p38 MAP kinases. Toxicology In Vitro 29 (5): 1146-1155. PMID: 25967738.
**70. Kim HK, Choi WS, Sorscher N, Tronche F, Palmiter RD, and Xia Z. (2015) Genetic reduction of mitochondrial complex I function does not lead to loss of dopamine neurons in vivo. Neurobiology of Aging 2015 Sep;36(9):2617-27. doi: 10.1016/j.neurobiolaging.2015.05.008. Epub 2015 May 16.
B. Refereed review articles, book chapters, and books
1. Choi EJ, Xia Z, Villacres EC, and Storm DR. (1993) The Regulatory Diversity of the Mammalian Adenylyl Cyclases. Cur. Opin. Cell Biol. 5: 269-273. PMID: 8507499
2. Villacres EC, Xia Z, Choi EJ, and Storm DR. (1993) Calmodulin Regulation of Mammalian Adenylyl Cyclases. Cur. Topics in Mol. Pharmacol. 1: 51-54.
3. Xia Z, Choi EJ, Blazynski C, and Storm DR. (1995) Do the Calmodulin Stimulated Adenylyl Cyclases Play a Role in Neuroplasticity? Behav. and Brain Sci. 18 (3): 429-440.
4. Xia Z and Storm DR. (1996) The Mammalian Adenylyl Cyclases. R. G. Landes Co. Mol. Bio. Intelligence Unit.
5. Xia Z and Storm DR. (1997) Calmodulin-regulated adenylyl cyclases and neuromodulation. Cur. Opin. Neurobiol. 7(3):391-396.
**6. Hetman M, Xia Z (2000) Signaling pathways mediating anti-apoptotic action of neurotrophins. Acta Neurobiol. Exp. 60:531-545. PMID: 11200182
7. Xia Z and Storm DR. (2002) CaRF, a Neuronal Transcription Factor that CaREs. Neuron 33: 315-316. PMID: 11832218
** 8. Xia Z. (2002) Adenylyl cyclases. Wiley Encyclopedia of Molecular Medicine. Edited by T. A. Creighton. 5: 79-82.
8. Xia Z, Storm DR. (2005) The role of calmodulin as a signal integrator for synaptic plasticity. Nat. Rev. Neurosci. 6(4):267-76. PMID: 15803158
**9. Dirocco, DP and Xia, Z (2007) Alpha males win again. Nat Neurosci. 10(8): 938-40. PMID: 17657234
** 10. Choi WS*, Klintworth HK*, Xia Z. (2011) JNK3-Mediated Apoptotic Cell Death in Primary Dopaminergic Neurons. Methods Mol Biol. 758:279-292. PMC3490420
11. Xia Z and Storm DR. (2012) Role of signal transduction crosstalk between adenylyl cyclase and MAP kinase in hippocampus-dependent memory. Learn Mem. 19(9):369-74. PMID: 22904367 PMCID: PMC3418765
** 12. Choi WS, Kim HW, Xia Z. (2013) Preparation of Primary Cultured Dopaminergic Neurons from Mouse Brain. Methods in Molecular Biology. 1018:61-9. PMID: 23681617 [PubMed - in process]
** 13. Pan YW, Wang WB and Xia Z. (2013) Assessment of Adult Neurogenesis in Mice. Curr Protoc Toxicol. Chapter 12:Unit12.20. PMID: 23670864 PMCID: PMC3683539
**14. Pan YW, Storm DR, Xia Z. (2013) Role of Adult Neurogenesis in Hippocampus-dependent Memory Formation Including Contextual Fear Extinction And Remote Contextual Fear Memory: Lessons from ERK5 MAP kinase. Neurobiology of Learning and Memory. 05:81-92 PMID: 23871742. PMC3782100
15. Chen, X., Xia, Z. and Storm, D. R. (2013). Electroolfactogram (EOG) Recording in the Mouse Main Olfactory Epithelium. Bio-protocol 3(11): e789. http://www.bio-protocol.org/e789
**16. Zou J, Wang W, Pan YW, Lu S, Xia Z. (2015) Methods to measure olfactory behavior in mice. Curr Protoc Toxicol. 2015 Feb 2;63:11.18.1-11.18.21. PMID: 25645244; PMCID: PMC4339283
Xia, Z. and Storm, D. R. (1996) The Mammalian Adenylyl Cyclases. R. G. Landes Co. Mol. Bio. Intelligence Unit.