Honors & Awards

  • Honors in Excellence in Research, University of California, Irvine, Dept of Biological Sciences (1999)
  • NIDA Training Grant - Predoctoral Fellowship, University of California, Irvine, Dept of Pharmacology (2001)
  • PhRMA Pharmacology/Toxicology Pre-Doctoral Fellowship, PhRMA Foundation (2003-2005)
  • Henry Wood Elliot Ph.D., M.D. Award, University of California, Irvine (2005)
  • Western States Affiliate, Postdoctoral Fellowship, American Heart Association (2005-2007)
  • NIH National Research Service Award Postdoctoral Fellowship (NRSA), NIH-NINDS (2008-2011)
  • Julius Axelrod Travel Award, Society for Neuroscience (2010)

Education & Certifications

  • Postdoc, Stanford University, Dept of Biology, Neuroscience and brain injury (2010)
  • PhD, University of California, Irvine, Dept of Pharmacology, Neuropharmacology (2005)
  • BS, University of California, Irvine, Biological Sciences (1999)


Professional Interests

My research interests include 1) mechanisms of neuron survival and recovery during injury; 2) use of molecular, pharmacological and optogenetic approaches to study neuronal circuits and plasticity during recovery; 3) identification of potential targets and biomarkers for neurological/neurodegenerative diseases.


All Publications

  • Optogenetic approaches to study stroke recovery. ACS chemical neuroscience Cheng, M. Y., Wang, E. H., Steinberg, G. K. 2014; 5 (12): 1144-1145


    Treatment for stroke is very limited, and potential new therapies are focusing on promoting brain repair and plasticity, as they offer a longer therapeutic time window than the current U.S. Food and Drug Administration approved drug. Functional recovery can occur after stroke, and strategies such as direct brain stimulations that promote recovery are promising. Here we review how selective stimulation of neurons in the motor cortex using optogenetics enhances plasticity mechanisms and promotes functional recovery after stroke.

    View details for DOI 10.1021/cn500216f

    View details for PubMedID 25259689

  • Optogenetic neuronal stimulation promotes functional recovery after stroke. Proceedings of the National Academy of Sciences of the United States of America Cheng, M. Y., Wang, E. H., Woodson, W. J., Wang, S., Sun, G., Lee, A. G., Arac, A., Fenno, L. E., Deisseroth, K., Steinberg, G. K. 2014; 111 (35): 12913-12918


    Clinical and research efforts have focused on promoting functional recovery after stroke. Brain stimulation strategies are particularly promising because they allow direct manipulation of the target area's excitability. However, elucidating the cell type and mechanisms mediating recovery has been difficult because existing stimulation techniques nonspecifically target all cell types near the stimulated site. To circumvent these barriers, we used optogenetics to selectively activate neurons that express channelrhodopsin 2 and demonstrated that selective neuronal stimulations in the ipsilesional primary motor cortex (iM1) can promote functional recovery. Stroke mice that received repeated neuronal stimulations exhibited significant improvement in cerebral blood flow and the neurovascular coupling response, as well as increased expression of activity-dependent neurotrophins in the contralesional cortex, including brain-derived neurotrophic factor, nerve growth factor, and neurotrophin 3. Western analysis also indicated that stimulated mice exhibited a significant increase in the expression of a plasticity marker growth-associated protein 43. Moreover, iM1 neuronal stimulations promoted functional recovery, as stimulated stroke mice showed faster weight gain and performed significantly better in sensory-motor behavior tests. Interestingly, stimulations in normal nonstroke mice did not alter motor behavior or neurotrophin expression, suggesting that the prorecovery effect of selective neuronal stimulations is dependent on the poststroke environment. These results demonstrate that stimulation of neurons in the stroke hemisphere is sufficient to promote recovery.

    View details for DOI 10.1073/pnas.1404109111

    View details for PubMedID 25136109

  • Prokineticin 2 is an endangering mediator of cerebral ischemic injury PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Cheng, M. Y., Lee, A. G., Culbertson, C., Sun, G., Talati, R. K., Manley, N. C., Li, X., Zhao, H., Lyons, D. M., Zhou, Q., Steinberg, G. K., Sapolsky, R. M. 2012; 109 (14): 5475-5480


    Stroke causes brain dysfunction and neuron death, and the lack of effective therapies heightens the need for new therapeutic targets. Here we identify prokineticin 2 (PK2) as a mediator for cerebral ischemic injury. PK2 is a bioactive peptide initially discovered as a regulator of gastrointestinal motility. Multiple biological roles for PK2 have been discovered, including circadian rhythms, angiogenesis, and neurogenesis. However, the role of PK2 in neuropathology is unknown. Using primary cortical cultures, we found that PK2 mRNA is up-regulated by several pathological stressors, including hypoxia, reactive oxygen species, and excitotoxic glutamate. Glutamate-induced PK2 expression is dependent on NMDA receptor activation and extracellular calcium. Enriched neuronal culture studies revealed that neurons are the principal source of glutamate-induced PK2. Using in vivo models of stroke, we found that PK2 mRNA is induced in the ischemic cortex and striatum. Central delivery of PK2 worsens infarct volume, whereas PK2 receptor antagonist decreases infarct volume and central inflammation while improving functional outcome. Direct central inhibition of PK2 using RNAi also reduces infarct volume. These findings indicate that PK2 can be activated by pathological stimuli such as hypoxia-ischemia and excitotoxic glutamate and identify PK2 as a deleterious mediator for cerebral ischemia.

    View details for DOI 10.1073/pnas.1113363109

    View details for Web of Science ID 000302294700073

    View details for PubMedID 22431614

  • An Insult-Inducible Vector System Activated by Hypoxia and Oxidative Stress for Neuronal Gene Therapy TRANSLATIONAL STROKE RESEARCH Cheng, M. Y., Lee, I., Jin, M., Sun, G., Zhao, H., Steinberg, G. K., Sapolsky, R. M. 2011; 2 (1): 92-100


    Gene therapy has demonstrated the protective potential of a variety of genes against stroke. However, conventional gene therapy vectors are limited due to the inability to temporally control their expression, which can sometimes lead to deleterious side effects. Thus, an inducible vector that can be temporally controlled and activated by the insult itself would be advantageous. Using hypoxia responsive elements (HRE) and antioxidant responsive elements (ARE), we have constructed an insult-inducible vector activated by hypoxia and reactive oxygen species (ROS). In COS7 cells, the inducible ARE-HRE-luciferase vectors are highly activated by oxygen deprivation, hydrogen peroxide treatment, and the ROS-induced transcription factor NF-E2-related factor 2 (Nrf2). Using a defective herpes virus, the neuroprotective potential of this inducible vector was tested by over-expressing the transcription factor Nrf2. In primary cortical cultures, expression of the inducible ARE-HRE-Nrf2 protects against oxygen glucose deprivation, similar to that afforded by the constitutively expressed Nrf2. This ARE+HRE vector system is advantageous in that it allows the expression of a transgene to be activated not only during hypoxia but also maintained after reperfusion, thus prolonging the transgene expression during an ischemic insult. This insult-inducible vector system will be a valuable gene therapy tool for activating therapeutic/protective genes in cerebrovascular diseases.

    View details for DOI 10.1007/s12975-010-0060-2

    View details for Web of Science ID 000304162800012

    View details for PubMedID 21603078

  • Blocking glucocorticoid and enhancing estrogenic genomic signaling protects against cerebral ischemia JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Cheng, M. Y., Sun, G., Jin, M., Zhao, H., Steinberg, G. K., Sapolsky, R. M. 2009; 29 (1): 130-136


    Glucocorticoids (GCs) and estrogen can modulate neuron death and dysfunction during neurological insults. Glucocorticoids are adrenal steroids secreted during stress, and hypersecretion of GCs during cerebral ischemia compromises the ability of hippocampal and cortical neurons to survive. In contrast, estrogen can be neuroprotective after cerebral ischemia. Here we evaluate the protective potential of a herpes viral vector expressing a chimeric receptor (ER/GR), which is composed of the ligand-binding domain of the GC receptor (GR) and the DNA-binding domain of the estrogen receptor-alpha (ER). This novel receptor can transduce an endangering GC signal into a protective estrogenic one. Using an in vitro oxygen glucose deprivation model (OGD), GCs exacerbated neuron death in primary cortical cultures, and this worsening effect was completely blocked by ER/GR expression. Moreover, blocking GC actions with a vector expressing a dominant negative GC receptor promoted neuron survival during postischemia, but not preischemia. Thus, gene therapeutic strategies to modulate GC and estrogen signaling can be beneficial during an ischemic insult.

    View details for DOI 10.1038/jcbfm.2008.105

    View details for Web of Science ID 000262110200015

    View details for PubMedID 18797472

  • Expression of prokineticins and their receptors in the adult mouse brain JOURNAL OF COMPARATIVE NEUROLOGY Cheng, M. Y., Leslie, F. M., Zhou, Q. 2006; 498 (6): 796-809


    Prokineticins are a pair of regulatory peptides that have been shown to play important roles in gastrointestinal motility, angiogenesis, circadian rhythms, and, recently, olfactory bulb neurogenesis. Prokineticins exert their functions via activation of two closely related G-protein-coupled receptors. Here we report a comprehensive mRNA distribution for both prokineticins (PK1 and PK2) and their receptors (PKR1 and PKR2) in the adult mouse brain with the use of in situ hybridization. PK2 mRNA is expressed in discrete regions of the brain, including suprachiasmatic nucleus, islands of Calleja and medial preoptic area, olfactory bulb, nucleus accumbens shell, hypothalamic arcuate nucleus, and amygdala. PK1 mRNA is expressed exclusively in the brainstem, with high abundance in the nucleus tractus solitarius. PKR2 mRNA is detected throughout the brain, with prominent expression in olfactory regions, cortex, thalamus and hypothalamus, septum and hippocampus, habenula, amygdala, nucleus tractus solitarius, and circumventricular organs such as subfornical organ, median eminence, and area postrema. PKR2 mRNA is also detected in mammillary nuclei, periaqueductal gray, and dorsal raphe. In contrast, PKR1 mRNA is found in fewer brain regions, with moderate expression in the olfactory regions, dentate gyrus, zona incerta, and dorsal motor vagal nucleus. Both PKR1 and PKR2 are also detected in olfactory ventricle and subventricular zone of the lateral ventricle, both of which are rich sources of neuronal precursors. These extensive expression patterns suggest that prokineticins may have a broad array of functions in the central nervous system, including circadian rhythm, neurogenesis, ingestive behavior, reproduction, and autonomic function.

    View details for DOI 10.1002/cne.21087

    View details for Web of Science ID 000240356400005

    View details for PubMedID 16927269

  • Dependence of olfactory bulb neurogenesis on prokineticin 2 signaling SCIENCE Ng, K. L., Li, J. D., Cheng, M. Y., Leslie, F. M., Lee, A. G., Zhou, Q. Y. 2005; 308 (5730): 1923-1927


    Neurogenesis persists in the olfactory bulb (OB) of the adult mammalian brain. New interneurons are continually added to the OB from the subventricular zone (SVZ) via the rostral migratory stream (RMS). Here we show that secreted prokineticin 2 (PK2) functions as a chemoattractant for SVZ-derived neuronal progenitors. Within the OB, PK2 may also act as a detachment signal for chain-migrating progenitors arriving from the RMS. PK2 deficiency in mice leads to a marked reduction in OB size, loss of normal OB architecture, and the accumulation of neuronal progenitors in the RMS. These findings define an essential role for G protein-coupled PK2 signaling in postnatal and adult OB neurogenesis.

    View details for DOI 10.1126/science.1112103

    View details for Web of Science ID 000230120000044

    View details for PubMedID 15976302

  • Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus NATURE Cheng, M. Y., Bullock, C. M., Li, C. Y., Lee, A. G., Bermak, J. C., Belluzzi, J., Weaver, D. R., Leslie, F. M., Zhou, Q. Y. 2002; 417 (6887): 405-410


    The suprachiasmatic nucleus (SCN) controls the circadian rhythm of physiological and behavioural processes in mammals. Here we show that prokineticin 2 (PK2), a cysteine-rich secreted protein, functions as an output molecule from the SCN circadian clock. PK2 messenger RNA is rhythmically expressed in the SCN, and the phase of PK2 rhythm is responsive to light entrainment. Molecular and genetic studies have revealed that PK2 is a gene that is controlled by a circadian clock (clock-controlled). Receptor for PK2 (PKR2) is abundantly expressed in major target nuclei of the SCN output pathway. Inhibition of nocturnal locomotor activity in rats by intracerebroventricular delivery of recombinant PK2 during subjective night, when the endogenous PK2 mRNA level is low, further supports the hypothesis that PK2 is an output molecule that transmits behavioural circadian rhythm. The high expression of PKR2 mRNA within the SCN and the positive feedback of PK2 on its own transcription through activation of PKR2 suggest that PK2 may also function locally within the SCN to synchronize output.

    View details for Web of Science ID 000175730900030

    View details for PubMedID 12024206

  • Mammalian Target of Rapamycin Cell Signaling Pathway Contributes to the Protective Effects of Ischemic Postconditioning Against Stroke STROKE Xie, R., Wang, P., Cheng, M., Sapolsky, R., Ji, X., Zhao, H. 2014; 45 (9): 2769-?


    Whether the mammalian target of rapamycin (mTOR) pathway is protective against brain injury from stroke or is detrimental is controversial, and whether it is involved in the protective effects of ischemic postconditioning (IPC) against stroke is unreported. Our study focuses on the protective role of mTOR against neuronal injury after stroke with and without IPC.We used both an in vitro oxygen-glucose deprivation model with a mixed neuronal culture and hypoxic postconditioning, as well as an in vivo stroke model with IPC. Rapamycin, a specific pharmacological inhibitor of mTOR, and mTOR short hairpin RNA lentiviral vectors were used to inhibit mTOR activity. A lentiviral vector expressing S6K1, a downstream molecule of mTOR, was used to confirm the protective effects of mTOR. Infarct sizes were measured and protein levels were examined by Western blot.We report that stroke resulted in reduced levels of phosphorylated proteins in the mTOR pathway, including S6K1, S6, and 4EBP1, and that IPC increased these proteins. mTOR inhibition, both by the mTOR inhibitor rapamycin and by mTOR short hairpin RNA, worsened ischemic outcomes in vitro and in vivo and abolished the protective effects of hypoxic postconditioning and IPC on neuronal death in vitro and brain injury size in vivo. Overexpression of S6K1 mediated by lentiviral vectors significantly attenuated brain infarction.mTOR plays a crucial protective role in brain damage after stroke and contributes to the protective effects of IPC.

    View details for DOI 10.1161/STROKEAHA.114.005406

    View details for Web of Science ID 000341491500055

    View details for PubMedID 25013017

  • PRAS40 plays a pivotal role in protecting against stroke by linking the Akt and mTOR pathways NEUROBIOLOGY OF DISEASE Xiong, X., Xie, R., Zhang, H., Gu, L., Xie, W., Cheng, M., Jian, Z., Kovacina, K., Zhao, H. 2014; 66: 43-52


    The proline-rich Akt substrate of 40kDa (PRAS40) protein is not only a substrate of the protein kinase Akt but also a component of the mTOR complex 1 (mTORC1), thus it links the Akt and the mTOR pathways. We investigated the potential protective role of PRAS40 in cerebral ischemia and its underlying mechanisms by using rats with lentiviral over-expression of PRAS40 and mice with PRAS40 gene knockout (PRAS40 KO). Our results show that gene transfer of PRAS40 reduced infarction size in rats by promoting phosphorylation of Akt, FKHR (FOXO1), PRAS40, and mTOR. In contrast, PRAS40 KO increased infarction size. Although the PRAS40 KO under normal condition did not alter baseline levels of phosphorylated proteins in the Akt and mTOR pathways, PRAS40 KO that underwent stroke exhibited reduced protein levels of p-S6K and p-S6 in the mTOR pathway but not p-Akt, or p-PTEN in the Akt pathway. Furthermore, co-immunoprecipitation suggests that there were less interactive effects between Akt and mTOR in the PRAS40 KO. In conclusion, PRAS40 appears to reduce brain injury by converting cell signaling from Akt to mTOR.

    View details for DOI 10.1016/j.nbd.2014.02.006

    View details for Web of Science ID 000335098600004

    View details for PubMedID 24583056

  • Akt isoforms differentially protect against stroke-induced neuronal injury by regulating mTOR activities JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Xie, R., Cheng, M., Li, M., Xiong, X., Daadi, M., Sapolsky, R. M., Zhao, H. 2013; 33 (12): 1875-1885


    Protein kinases Akt1 and Akt3 are considered to be more crucial to brain function than Akt2. We investigated the roles of Akt1 and Akt3 in stroke-induced brain injury and examined their interactions with the Akt/mTOR pathways. Focal ischemia was induced in rats. Lentiviral vectors expressing constitutively active Akt1 and Akt3 (cAkt1 and cAkt3) were injected into the ischemic cortex. Infarct sizes and gene and protein expressions in the Akt/mTOR pathways were evaluated. The results show that Akt1 and Akt3 proteins were degraded as early as 1?hour after stroke, whereas Akt2 proteins remained unchanged until 24?hours after stroke. Lentiviral-mediated overexpression of cAkt1 or cAkt3 reduced neuronal death after in vitro and in vivo ischemia. Interestingly, cAkt3 overexpression resulted in stronger protection than cAkt1 overexpression. Western blot analyses further showed that cAkt3 promoted significantly higher levels of phosphorylated Akt and phosphorylated mTOR than cAkt1. The mTOR inhibitor rapamycin blocked the protective effects of both cAkt1 and cAkt3. In conclusion, Akt isoforms are differentially regulated after stroke and Akt3 offers stronger protection than cAkt1 by maintaining Akt levels and promoting mTOR activity.

    View details for DOI 10.1038/jcbfm.2013.132

    View details for Web of Science ID 000328002200008

    View details for PubMedID 23942361

  • Prokineticin 2 is involved in the thermoregulation and energy expenditure REGULATORY PEPTIDES Zhou, W., Li, J., Hu, W., Cheng, M. Y., Zhou, Q. 2012; 179 (1-3): 84-90


    Animals have developed adaptive strategies to survive tough situations such as food shortage. However, the underlying molecular mechanism is not fully understood. Here, we provided evidence that the regulatory peptide prokineticin 2 (PK2) played an important role in such an adaptation. The PK2 expression was rapidly induced in the hypothalamic paraventricular nucleus (PVN) after fasting, which can be mimicked by 2-deoxy-D-glucose (2-DG) injection. The fasting-induced arousal was absent in the PK2-deficient (PK2(-/-)) mice. Furthermore, PK2(-/-) mice showed less energy expenditure and body weight loss than wild-type (WT) controls upon fasting. As a result, PK2(-/-) mice entered torpor after fasting. Supply of limited food (equal to 5% of body weight) daily during fasting rescued the body weight loss and hypothermal phenotype in WT mice, but not in PK2(-/-) mice. Our study thus demonstrated PK2 as a regulator in the thermoregulation and energy expenditure.

    View details for DOI 10.1016/j.regpep.2012.08.003

    View details for Web of Science ID 000311186000015

    View details for PubMedID 22960406

  • A novel form of oxytocin in New World monkeys BIOLOGY LETTERS Lee, A. G., Cool, D. R., Grunwald, W. C., Neal, D. E., Buckmaster, C. L., Cheng, M. Y., Hyde, S. A., Lyons, D. M., Parker, K. J. 2011; 7 (4): 584-587


    Oxytocin is widely believed to be present and structurally identical in all placental mammals. Here, we report that multiple species of New World monkeys possess a novel form of oxytocin, [P8] oxytocin. This mutation arises from a substitution of a leucine to a proline in amino acid position 8. Further analysis of this mutation in Saimiri sciureus (squirrel monkey) indicates that [P8] oxytocin is transcribed and translated properly. This mutation is specific to oxytocin, as the peptide sequence for arginine vasopressin, a structurally related nonapeptide, is unaltered. These findings dispel the notion that all placental mammals possess a 'universal' oxytocin sequence, and highlight the need for research on the functional significance of this novel nonapeptide in New World monkeys.

    View details for DOI 10.1098/rsbl.2011.0107

    View details for Web of Science ID 000292639100031

    View details for PubMedID 21411453

  • Attenuated circadian rhythms in mice lacking the prokineticin 2 gene JOURNAL OF NEUROSCIENCE Li, J., Hu, W., Boehmer, L., Cheng, M. Y., Lee, A. G., Jilek, A., Siegel, J. M., Zhou, Q. 2006; 26 (45): 11615-11623


    Circadian clocks drive daily rhythms in virtually all organisms. In mammals, the suprachiasmatic nucleus (SCN) is recognized as the master clock that synchronizes central and peripheral oscillators to evoke circadian rhythms of diverse physiology and behavior. How the timing information is transmitted from the SCN clock to generate overt circadian rhythms is essentially unknown. Prokineticin 2 (PK2), a clock-controlled gene that encodes a secreted protein, has been indicated as a candidate SCN clock output signal that regulates circadian locomotor rhythm. Here we report the generation and analysis of PK2-null mice. The reduction of locomotor rhythms in PK2-null mice was apparent in both hybrid and inbred genetic backgrounds. PK2-null mice also displayed significantly reduced rhythmicity for a variety of other physiological and behavioral parameters, including sleep-wake cycle, body temperature, circulating glucocorticoid and glucose levels, as well as the expression of peripheral clock genes. In addition, PK2-null mice showed accelerated acquisition of food anticipatory activity during a daytime food restriction. We conclude that PK2, acting as a SCN output factor, is important for the maintenance of robust circadian rhythms.

    View details for DOI 10.1523/JNEUROSCI.3679-06.2006

    View details for Web of Science ID 000241892700013

    View details for PubMedID 17093083

  • Nicotine modulation of stress-related peptide neurons JOURNAL OF COMPARATIVE NEUROLOGY Loughlin, S. E., Islas, M. I., Cheng, M. Y., Lee, A. G., Villegier, A., Leslie, F. M. 2006; 497 (4): 575-588


    Nicotine has been shown to activate stress-related brain nuclei, including the paraventricular nucleus of the hypothalamus (PVN) and the central nucleus of the amygdala (CEA), through complex mechanisms involving direct and indirect pathways. To determine the neurochemical identities of rat brain neurons which are activated by a low dose (0.175 mg/kg) of nicotine given 30 minutes before sacrifice, we have used single- and double-label in situ hybridization. Neuronal activation was quantified by localization of (35)S-labeled probe for the immediate early gene, c-fos. Corticotrophin releasing factor (CRF), enkephalin (ENK), and dynorphin (DYN) mRNAs were colocalized using a colorimetric, digoxigenin-labeled probe. Film autoradiographic studies showed that nicotine significantly increased c-fos mRNA expression in both PVN and CEA. Pretreatment with the centrally acting nicotinic antagonist, mecamylamine (1 mg/kg), blocked nicotine's effects, whereas pretreatment with the peripherally acting antagonist, hexamethonium (5 mg/kg), did not, indicating that c-fos induction was mediated by a central nicotinic receptor. Double labeling studies showed that nicotine induced c-fos expression within CRF cells in the PVN, as well as in a small population of ENK cells, but not in PVN DYN cells. In contrast, there was no significant nicotine-induced increase in c-fos expression in CEA CRF or DYN cells, whereas nicotine treatment did increase c-fos expression within CEA ENK cells.

    View details for DOI 10.1002/cne.20999

    View details for Web of Science ID 000238490800004

    View details for PubMedID 16739166

  • Prokineticin 2 and circadian clock output FEBS JOURNAL Zhou, Q. Y., Cheng, M. Y. 2005; 272 (22): 5703-5709


    Circadian timing from the suprachiasmatic nucleus (SCN) is a critical component of sleep regulation. Animal lesion and genetic studies have indicated an essential interaction between the circadian signals and the homeostatic processes that regulate sleep. Here we summarize the biological functions of prokineticins, a pair of newly discovered regulatory proteins, with focus on the circadian function of prokineticin 2 (PK2) and its potential role in sleep-wake regulation. PK2 has been shown as a candidate SCN output molecule that regulates circadian locomotor behavior. The PK2 molecular rhythm in the SCN is predominantly controlled by the circadian transcriptional/translational loops, but also regulated directly by light. The receptor for PK2 is expressed in the primary SCN output targets that regulate circadian behavior including sleep-wake. The depolarizing effect of PK2 on neurons that express PK2 receptor may represent a possible mechanism for the regulatory role of PK2 in circadian rhythms.

    View details for DOI 10.1111/j.1742-4658.2005.04984.x

    View details for Web of Science ID 000233143600005

    View details for PubMedID 16279936

  • Regulation of prokineticin 2 expression by light and the circadian clock BMC NEUROSCIENCE Cheng, M. Y., Bittman, E. L., Hattar, S., Zhou, Q. Y. 2005; 6


    The suprachiasmatic nucleus (SCN) contains the master circadian clock that regulates daily rhythms of many physiological and behavioural processes in mammals. Previously we have shown that prokineticin 2 (PK2) is a clock-controlled gene that may function as a critical SCN output molecule responsible for circadian locomotor rhythms. As light is the principal zeitgeber that entrains the circadian oscillator, and PK2 expression is responsive to nocturnal light pulses, we further investigated the effects of light on the molecular rhythm of PK2 in the SCN. In particular, we examined how PK2 responds to shifts of light/dark cycles and changes in photoperiod. We also investigated which photoreceptors are responsible for the light-induced PK2 expression in the SCN. To determine whether light requires an intact functional circadian pacemaker to regulate PK2, we examined PK2 expression in cryptochrome1,2-deficient (Cry1-/-Cry2-/-) mice that lack functional circadian clock under normal light/dark cycles and constant darkness.Upon abrupt shifts of the light/dark cycle, PK2 expression exhibits transients in response to phase advances but rapidly entrains to phase delays. Photoperiod studies indicate that PK2 responds differentially to changes in light period. Although the phase of PK2 expression expands as the light period increases, decreasing light period does not further condense the phase of PK2 expression. Genetic knockout studies revealed that functional melanopsin and rod-cone photoreceptive systems are required for the light-inducibility of PK2. In Cry1-/-Cry2-/- mice that lack a functional circadian clock, a low amplitude PK2 rhythm is detected under light/dark conditions, but not in constant darkness. This suggests that light can directly regulate PK2 expression in the SCN.These data demonstrate that the molecular rhythm of PK2 in the SCN is regulated by both the circadian clock and light. PK2 is predominantly controlled by the endogenous circadian clock, while light plays a modulatory role. The Cry1-/-Cry2-/- mice studies reveal a light-driven PK2 rhythm, indicating that light can induce PK2 expression independent of the circadian oscillator. The light inducibility of PK2 suggests that in addition to its role in clock-driven rhythms of locomotor behaviour, PK2 may also participate in the photic entrainment of circadian locomotor rhythms.

    View details for DOI 10.1186/1471-2202-6-17

    View details for Web of Science ID 000227950100002

    View details for PubMedID 15762991

  • Expression of the melanin-concentrating hormone (MCH) receptor mRNA in the rat brain JOURNAL OF COMPARATIVE NEUROLOGY Saito, Y., Cheng, M., Leslie, F. M., Civelli, O. 2001; 435 (1): 26-40


    The melanin-concentrating hormone (MCH) system is thought to be an important regulator of food intake. Recently the orphan G protein-coupled receptor SLC-1 was identified as the MCH receptor (MCHR). Preliminary analyses of MCHR mRNA distribution have supported a role for the MCH system in nutritional homeostasis. We report here a complete anatomical distribution of the MCHR mRNA. We have found high levels of expression of MCHR mRNA in most anatomical areas implicated in control of olfaction, with the exception of the main olfactory bulb. Dense labeling was also detected in the hippocampal formation, subiculum, and basolateral amygdala, all of which are important in learning and memory, and in the shell of the nucleus accumbens, a substrate for motivated behavior and feeding. Within the hypothalamus, MCHR mRNA was moderately expressed in the ventromedial nucleus, arcuate nucleus, and zona incerta, all of which serve key roles in the neuronal circuitry of feeding. In the brainstem, strong expression was observed in the locus coeruleus, which is implicated in arousal, as well as in nuclei that contribute to orofacial function and mastication, including the facial, hypoglossal, motor trigeminal, and dorsal motor vagus nuclei. In most regions there was a good correspondence between MCHR mRNA distribution and that of MCH-immunoreactive fibers. Taken together, these data suggest that MCH may act at various levels of the brain to integrate various aspects of feeding behavior. However, the extensive MCHR distribution throughout the brain suggests that this receptor may play a role in other functions, most notably reinforcement, arousal, sensorimotor integration, and autonomic control.

    View details for Web of Science ID 000168841100003

    View details for PubMedID 11370009

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