Skip to main content Accessibility help
×
Home
  • Print publication year: 2011
  • Online publication date: November 2011

6 - Cannabis, endocannabinoids and neurodevelopment

Summary

The impact of prenatal cannabinoid exposure on brain development and interest in understanding its interference with normal adult neurological function has fostered the characterization of the endocannabinoid system (ECS) during nervous system development. Multiple lines of evidences show that the ECS regulates the functionality of neural progenitor cell populations during development and in adult neurogenic areas. CB1 receptors allow crosstalk with growth factor and neurotrophin signaling at different levels. The glutamatergic neuronal dysfunction hypothesis of schizophrenia suggests that malfunction of the developmental role of CB1 receptors in pyramidal neurogenesis may contribute to the pathogenesis of psychoses or schizophrenia symptoms. Recent findings have demonstrated that endocannabinoids and CB1 receptors are crucial regulators of neurogenic processes including neural progenitor cell proliferation and survival, neuronal specification, migration, synapse establishment and the correct connectivity of newly formed cells. The ECS may be considered as a novel regulatory signaling system of neurogenesis and nervous system maturation.

Related content

Powered by UNSILO

References

Aguado, T., Monory, K., Palazuelos, J., et al. (2005) The endocannabinoid system drives neural progenitor proliferation. FASEB J, 19:1704–6.
Aguado, T., Palazuelos, J., Monory, K., et al. (2006) The endocannabinoid system promotes astroglial differentiation by acting on neural progenitor cells. J Neurosci, 26:1551–61.
Aguado, T., Romero, E., Monory, K., et al. (2007) The CB1 cannabinoid receptor mediates excitotoxicity-induced neural progenitor proliferation and neurogenesis. J Biol Chem, 282:23892–8.
Antonelli, T., Tomasini, M.C., Tattoli, M., et al. (2005) Prenatal exposure to the CB1 receptor agonist WIN 55,212–2 causes learning disruption associated with impaired cortical NMDA receptor function and emotional reactivity changes in rat offspring. Cereb Cortex, 15:2013–20.
Arevalo-Martin, A., Garcia-Ovejero, D., Gomez, O., et al. (2008) CB2 cannabinoid receptors as an emerging target for demyelinating diseases: from neuroimmune interactions to cell replacement strategies. Brit J Pharmacol, 153:216–25.
Arevalo-Martin, A., Garcia-Ovejero, D., Rubio-Araiz, A., et al. (2007) Cannabinoids modulate Olig2 and polysialylated neural cell adhesion molecule expression in the subventricular zone of post-natal rats through cannabinoid receptor 1 and cannabinoid receptor 2. Eur J Neurosci, 26:1548–59.
Argaw, A., Duff, G., Zabouri, N., et al. (2011) Concerted action of CB1 cannabinoid receptor and deleted in colorectal cancer in axon guidance. J. Neurosci, 31:1489–99.
Aso, E., Ozaita, A., Valdizan, E.M., et al. (2008) BDNF impairment in the hippocampus is related to enhanced despair behavior in CB1 knockout mice. J Neurochem, 105:565–72.
Begbie, J., Doherty, P. and Graham, A. (2004) Cannabinoid receptor, CB1, expression follows neuronal differentiation in the early chick embryo. J Anat, 205:213–8.
Benagiano, V., Lorusso, L., Flace, P., et al. (2007) Effects of prenatal exposure to the CB-1 receptor agonist WIN 55212–2 or CO on the GABAergic neuronal systems of rat cerebellar cortex. Neuroscience, 149:592–601.
Bergami, M., Rimondini, R., Santi, S., Blum, R., Gotz, M. and Canossa, M. (2008) Deletion of TrkB in adult progenitors alters newborn neuron integration into hippocampal circuits and increases anxiety-like behavior. Proc Natl Acad Sci U S A, 105:15570–5.
Berghuis, P., Dobszay, M.B., Wang, X., et al. (2005) Endocannabinoids regulate interneuron migration and morphogenesis by transactivating the TrkB receptor. Proc Natl Acad Sci USA, 102:19115–20.
Berghuis, P., Rajnicek, A.M., Morozov, Y.M., et al. (2007) Hardwiring the brain: endocannabinoids shape neuronal connectivity. Science, 316:1212–6.
Bernard, C., Milh, M., Morozov, Y.M., Ben-Ari, Y., Freund, T.F. and Gozlan, H. (2005) Altering cannabinoid signaling during development disrupts neuronal activity. Proc Natl Acad Sci USA, 102:9388–93.
Berrendero, F., GarciaGil, L., Hernandez, M.L., et al. (1998) Localization of mRNA expression and activation of signal transduction mechanisms for cannabinoid receptor in rat brain during fetal development. Development, 125:3179–88.
Berrendero, F., Sepe, N., Ramos, J.A., Di Marzo, V. and Fernandez-Ruiz, J.J. (1999) Analysis of cannabinoid receptor binding and mRNA expression and endogenous cannabinoid contents in the developing rat brain during late gestation and early postnatal period. Synapse, 33:181–91.
Bilkei-Gorzo, A., Racz, I., Valverde, O., et al. (2005) Early age-related cognitive impairment in mice lacking cannabinoid CB1 receptors. Proc Natl Acad Sci USA, 102:15670–5.
Bisogno, T., Howell, F., Williams, G., et al. (2003) Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brain. J Cell Biol, 163:463–8.
Bodor, A.L., Katona, I., Nyiri, G., et al. (2005) Endocannabinoid signaling in rat somatosensory cortex: laminar differences and involvement of specific interneuron types. J Neurosci, 25:6845–56.
Bromberg, K.D., Ma’ayan, A., Neves, S.R. and Iyengar, R. (2008) Design logic of a cannabinoid receptor signaling network that triggers neurite outgrowth. Science, 320:903–9.
Carracedo, A., Lorente, M., Egia, A., et al. (2006) The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells. Cancer Cell, 9:301–12.
Castaldo, P., Magi, S., Gaetani, S., et al. (2007) Prenatal exposure to the cannabinoid receptor agonist WIN 55,212–2 increases glutamate uptake through overexpression of GLT1 and EAAC1 glutamate transporter subtypes in rat frontal cerebral cortex. Neuropharmacology, 53:369–378.
Cobos, I., Calcagnotto, M.E., Vilaythong, A.J., et al. (2005) Mice lacking Dlx1 show subtype-specific loss of interneurons, reduced inhibition and epilepsy. Nat Neurosci, 8:1059–68.
Chen, K., Neu, A., Howard, A.L., et al. (2007) Prevention of plasticity of endocannabinoid signaling inhibits persistent limbic hyperexcitability caused by developmental seizures. J Neurosci, 27:46–58.
Chen, K., Ratzliff, A., Hilgenberg, L., et al. (2003) Long-term plasticity of endocannabinoid signaling induced by developmental febrile seizures. Neuron, 39, 599–611.
D’Souza, D.C., Sewell, R.A. and Ranganathan, M. (2009) Cannabis and psychosis/schizophrenia: human studies. Eur Arch Psychiatry Clin Neurosci, 259:413–31.
Danzer, S.C. (2008) Postnatal and adult neurogenesis in the development of human disease. Neuroscientist, 14:446–58.
Davis, M.I., Ronesi, J. and Lovinger, D.M. (2003) A predominant role for inhibition of the adenylate cyclase/protein kinase A pathway in ERK activation by cannabinoid receptor 1 in N1E-115 neuroblastoma cells. J Biol Chem, 278:48973–80.
De March, Z., Zuccato, C., Giampa, C., et al. (2008) Cortical expression of brain derived neurotrophic factor and type-1 cannabinoid receptor after striatal excitotoxic lesions. Neuroscience, 152:734–40.
Eggan, S.M., Hashimoto, T. and Lewis, D.A. (2008) Reduced cortical cannabinoid 1 receptor messenger RNA and protein expression in schizophrenia. Arch Gen Psychiatry, 65:772–84.
Ehninger, D., Li, W., Fox, K., Stryker, M.P. and Silva, A.J. (2008) Reversing neurodevelopmental disorders in adults. Neuron, 60:950–60.
Fiskerstrand, T., H’mida-Ben Brahim, D., Johansson, S., et al. (2010) Mutations in ABHD12 cause the neurodegenerative disease PHARC: An inborn error of endocannabinoid metabolism. Am J Hum Genet, 87:410–17.
Freund, T.F., Katona, I. and Piomelli, D. (2003) Role of Endogenous Cannabinoids in Synaptic Signaling. Physiol Rev, 83:1017–66.
Fukuda, S., Abematsu, M., Mori, H., et al. (2007) Potentiation of astrogliogenesis by STAT3-mediated activation of bone morphogenetic protein-Smad signaling in neural stem cells. Mol Cell Biol, 27:4931–7.
Galve-Roperh, I., Aguado, T., Palazuelos, J. and Guzman, M. (2007) The endocannabinoid system and neurogenesis in health and disease. Neuroscientist, 13, 109–14.
Galve-Roperh, I., Aguado, T., Palazuelos, J. and Guzman, M. (2008) Mechanisms of control of neuron survival by the endocannabinoid system. Curr Pharm Des, 14:2279–88.
Galve-Roperh, I., Palazuelos, J., Aguado, T. and Guzman, M. (2009) The endocannabinoid system and the regulation of neural development: potential implications in psychiatric disorders. Eur Arch Psychiatry Clin Neurosci, 259:371–82.
Galve-Roperh, I., Rueda, D., Gomez Del Pulgar, T., Velasco, G. and Guzman, M. (2002) Mechanism of Extracellular Signal-Regulated Kinase Activation by the CB(1) Cannabinoid Receptor. Mol Pharmacol, 62:1385–92.
Garcia-Ovejero, D., Arevalo-Martin, A., Petrosino, S., et al. (2009) The endocannabinoid system is modulated in response to spinal cord injury in rats. Neurobiol Dis, 33:57–71.
Gomez, M., Hernandez, M. and Fernandez-Ruiz, J. (2007) The activation of cannabinoid receptors during early postnatal development reduces the expression of cell adhesion molecule L1 in the rat brain. Brain Res, 1145:48–55.
Goncalves, M.B., Suetterlin, P., Yip, P., et al. (2008) A diacylglycerol lipase-CB2 cannabinoid pathway regulates adult subventricular zone neurogenesis in an age-dependent manner. Mol Cell Neurosci, 38:526–36.
Guillemot, F., Molnar, Z., Tarabykin, V. and Stoykova, A. (2006) Molecular mechanisms of cortical differentiation. Eur J Neurosci, 23:857–68.
Guzman, M. (2003) Neurons on cannabinoids: dead or alive?Br J Pharmacol, 140:439–40.
Hariri, A.R., Gorka, A., Hyde, L.W., et al. (2009) Divergent effects of genetic variation in endocannabinoid signaling on human threat- and reward-related brain function. Biol Psychiatry, 66:9–16.
Harkany, T., Guzman, M., Galve-Roperh, I., Berghuis, P., Devi, L.A. and Mackie, K. (2007) The emerging functions of endocannabinoid signaling during CNS development. Trends Pharmacol Sci, 28:83–92.
Hart, S., Fischer, O.M. and Ullrich, A. (2004) Cannabinoids induce cancer cell proliferation via tumor necrosis factor alpha-converting enzyme (TACE/ADAM17)-mediated transactivation of the epidermal growth factor receptor. Cancer Res, 64:1943–50.
Hashimotodani, Y., Ohno-Shosaku, T. and Kano, M. (2007) Endocannabinoids and synaptic function in the CNS. Neuroscientist, 13:127–37.
He, J.C., Gomes, I., Nguyen, T., et al. (2005a) The G alpha (o/i)-coupled cannabinoid receptor-mediated neurite outgrowth involves Rap regulation of Src and Stat3. J Biol Chem, 280: 33426–34.
Heifets, B.D. and Castillo, P.E. (2009) Endocannabinoid signaling and long-term synaptic plasticity. Annu Rev Physiol, 71:283–306.
Heng, J.I., Moonen, G. and Nguyen, L. (2007) Neurotransmitters regulate cell migration in the telencephalon. Eur J Neurosci, 26:537–46.
Hill, M.N., Kambo, J.S., Sun, J.C., Gorzalka, B.B. and Galea, L.A. (2006) Endocannabinoids modulate stress-induced suppression of hippocampal cell proliferation and activation of defensive behaviors. Eur J Neurosci, 24:1845–9.
Hill, M.N., Titterness, A.K., Morrish, A.C., et al. (2009) Endogenous cannabinoid signaling is required for voluntary exercise-induced enhancement of progenitor cell proliferation in the hippocampus. Hippocampus, 20:513–23.
Ishii, I. and Chun, J. (2002) Anandamide-induced neuroblastoma cell rounding via the CB1 cannabinoid receptors. Neuroreport, 13:593–6.
Jakubs, K., Nanobashvili, A., Bonde, S., et al. (2006) Environment matters: synaptic properties of neurons born in the epileptic adult brain develop to reduce excitability. Neuron, 52:1047–59.
Jiang, S., Fu, Y., Williams, J., et al. (2007) Expression and function of cannabinoid receptors CB1 and CB2 and their cognate cannabinoid ligands in murine embryonic stem cells. PLoS ONE, 2:e641.
Jiang, W., Zhang, Y., Xiao, L., et al. (2005) Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects. J Clin Invest, 115:3104–16.
Jin, K., Xie, L., Kim, S.H., et al. (2004) Defective Adult Neurogenesis in CB1 Cannabinoid Receptor Knockout Mice. Mol Pharmacol, 66:204–8.
Jordan, J.D., He, J.C., Eungdamrong, N.J., et al. (2005) Cannabinoid receptor-induced neurite outgrowth is mediated by Rap1 activation through G(alpha)o/i-triggered proteasomal degradation of Rap1GAPII. J Biol Chem, 280:11413–21.
Jutras-Aswad, D., DiNieri, J.A., Harkany, T. and Hurd, Y.L. (2009) Neurobiological consequences of maternal cannabis on human fetal development and its neuropsychiatric outcome. Eur Arch Psychiatry Clin Neurosci, 259:395–412.
Katona, I. and Freund, T.F. (2008) Endocannabinoid signaling as a synaptic circuit breaker in neurological disease. Nat Med, 14:923–30.
Katona, I., Urban, G.M., Wallace, M., et al. (2006) Molecular composition of the endocannabinoid system at glutamatergic synapses. J Neurosci, 26:5628–37.
Kawamura, Y., Fukaya, M., Maejima, T., et al. (2006) The CB1 cannabinoid receptor is the major cannabinoid receptor at excitatory presynaptic sites in the hippocampus and cerebellum. J Neurosci, 26:2991–3001.
Kim, D. and Thayer, S.A. (2001) Cannabinoids inhibit the formation of new synapses between hippocampal neurons in culture. J Neurosci, 21:RC146.
Kim, H.J., Waataja, J.J. and Thayer, S.A. (2008) Cannabinoids inhibit network-driven synapse loss between hippocampal neurons in culture. J Pharmacol Exp Ther, 325:850–8.
Kowalczyk, T., Pontious, A., Englund, C., et al. (2009) Intermediate neuronal progenitors (basal progenitors) produce pyramidal-projection neurons for all layers of cerebral cortex. Cereb Cortex, 19:2439–50.
Krebs-Kraft, D.L., Hill, M.N., Hillard, C.J., et al. (2010) Sex difference in cell proliferation in developing rat amygdala mediated by endocannabinoids has implications for soical behavior. Proc Natl Acad Sci U S A, 107:20535–40.
Lafourcade, M., Elezgarai, I., Mato, S., Bakiri, Y., Grandes, P. and Manzoni, O.J. (2007) Molecular components and functions of the endocannabinoid system in mouse prefrontal cortex. PLoS ONE, 2:e709.
Li, L., Bender, K.J., Drew, P.J., Jadhav, S.P., Sylwestrak, E. and Feldman, D.E. (2009) Endocannabinoid signaling is required for development and critical period plasticity of the whisker map in somatosensory cortex. Neuron, 64:537–49.
Lutz, B. and Monory, K. (2008) Soothing the seizures of children. Nat Med, 14:721–2.
Mackie, K. (2006) Cannabinoid receptors as therapeutic targets. Annu Rev Pharmacol Toxicol, 46:101–22.
Mackowiak, M., Chocyk, A., Markowicz-Kula, K. and Wedzony, K. (2007) Acute activation of CB1 cannabinoid receptors transiently decreases PSA-NCAM expression in the dentate gyrus of the rat hippocampus. Brain Res, 1148:43–52.
Manent, J.B., Wang, Y., Chang, Y., Paramasivam, M. and LoTurco, J.J. (2009) Dcx reexpression reduces subcortical band heterotopia and seizure threshold in an animal model of neuronal migration disorder. Nat Med, 15:84–90.
Marchalant, Y., Brothers, H.M., Norman, G.J., Karelina, K., DeVries, A.C. and Wenk, G.L. (2009a) Cannabinoids attenuate the effects of aging upon neuroinflammation and neurogenesis. Neurobiol Dis, 34:300–7.
Marchalant, Y., Brothers, H.M. and Wenk, G.L. (2009b) Cannabinoid agonist WIN-55,212–2 partially restores neurogenesis in the aged rat brain. Mol Psychiatry, 14:1068–9.
Maresz, K., Pryce, G., Ponomarev, E.D., et al. (2007) Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB(1) on neurons and CB(2) on autoreactive T cells. Nat Med, 13:492–7.
Marsicano, G., Goodenough, S., Monory, K., et al. (2003) CB1 cannabinoid receptors and on-demand defense against excitotoxicity. Science, 302:84–8.
Marsicano, G., Wotjak, C.T., Azad, S.C., et al. (2002) The endogenous cannabinoid system controls extinction of aversive memories. Nature, 418:530–4.
Martinez-Gras, I., Hoenicka, J., Ponce, G., et al. (2006) (AAT)n repeat in the cannabinoid receptor gene, CNR1: association with schizophrenia in a Spanish population. EurArch Psychiatry Clin Neurosci, 256:437–41.
Mato, S., Del Olmo, E. and Pazos, A. (2003) Ontogenetic development of cannabinoid receptor expression and signal transduction functionality in the human brain. Eur J Neurosci, 17:1747–54.
Mereu, G., Fa, M., Ferraro, L., et al. (2003) Prenatal exposure to a cannabinoid agonist produces memory deficits linked to dysfunction in hippocampal long-term potentiation and glutamate release. Proc Natl Acad Sci USA, 100:4915–20.
Molina-Holgado, E., Vela, J.M., Arevalo-Martin, A., et al. (2002) Cannabinoids promote oligodendrocyte progenitor survival: involvement of cannabinoid receptors and phosphatidylinositol-3 kinase/Akt signaling. J Neurosci, 22:9742–53.
Monory, K., Massa, F., Egertova, M., et al. (2006) The endocannabinoid system controls key epileptogenic circuits in the hippocampus. Neuron, 51:455–66.
Morozov, Y.M. and Freund, T.F. (2003) Post-natal development of type 1 cannabinoid receptor immunoreactivity in the rat hippocampus. Eur J Neurosci, 18:1213–22.
Morozov, Y.M., Torii, M. and Rakic, P. (2009) Origin, early commitment, migratory routes, and destination of cannabinoid type 1 receptor-containing interneurons. Cereb Cortex, 19 Suppl 1:i78–89.
Mulder, J., Aguado, T., Keimpema, E., et al. (2008) Endocannabinoid signaling controls pyramidal cell specification and long-range axon patterning. Proc Natl Acad Sci USA, 105:8760–5.
Nakamura, K., Salomonis, N., Tomoda, K., Yamanaka, S. and Conklin, B.R. (2009) G(i)-coupled GPCR signaling controls the formation and organization of human pluripotent colonies. PLoS One, 4:e7780.
Norrod, A.G. and Puffenbarger, R.A. (2007) Genetic polymorphisms of the endocannabinoid system. Chem Biodivers, 4:1926–32.
Nosten-Bertrand, M., Kappeler, C., Dinocourt, C., et al. (2008) Epilepsy in Dcx knockout mice associated with discrete lamination defects and enhanced excitability in the hippocampus. PLoS One, 3:e2473.
Onaivi, E.S., Ishiguro, H., Gong, J.P., et al. (2008) Brain neuronal CB2 cannabinoid receptors in drug abuse and depression: from mice to human subjects. PLoS ONE, 3:e1640.
Osumi, N., Shinohara, H., Numayama-Tsuruta, K. and Maekawa, M. (2008) Concise review: Pax6 transcription factor contributes to both embryonic and adult neurogenesis as a multifunctional regulator. Stem Cells, 26:1663–72.
Overstreet-Wadiche, L.S., Bromberg, D.A., Bensen, A.L. and Westbrook, G.L. (2006) Seizures accelerate functional integration of adult-generated granule cells. J Neurosci, 26, 4095–103.
Palazuelos, J., Aguado, T., Egia, A., Mechoulam, R., Guzman, M. and Galve-Roperh, I. (2006) Non-psychoactive CB2 cannabinoid agonists stimulate neural progenitor proliferation. FASEB J, 20:2405–407.
Palazuelos, J., Aguado, T., Pazos, M.R., et al. (2009) Microglial CB2 cannabinoid receptors are neuroprotective in Huntington’s disease excitotoxicity. Brain, 132:3152–64.
Pang, T., Atefy, R. and Sheen, V. (2008) Malformations of cortical development. Neurologist, 14:181–91.
Parent, J.M. and Murphy, G.G. (2008) Mechanisms and functional significance of aberrant seizure-induced hippocampal neurogenesis. Epilepsia, 49 Suppl 5:19–25.
Patel, S. and Hillard, C.J. (2008) Adaptations in endocannabinoid signaling in response to repeated homotypic stress: a novel mechanism for stress habituation. Eur J Neurosci, 27:2821–9.
Paz, R.D., Tardito, S., Atzori, M. and Tseng, K.Y. (2008) Glutamatergic dysfunction in schizophrenia: from basic neuroscience to clinical psychopharmacology. Eur Neuropsychopharmacol, 18:773–86.
Ponce, G., Hoenicka, J., Rubio, G., et al. (2003) Association between cannabinoid receptor gene (CNR1) and childhood attention deficit/hyperactivity disorder in Spanish male alcoholic patients. Mol Psychiatry, 8:466–7.
Powell, E.M., Campbell, D.B., Stanwood, G.D., Davis, C., Noebels, J.L. and Levitt, P. (2003) Genetic disruption of cortical interneuron development causes region- and GABA cell type-specific deficits, epilepsy, and behavioral dysfunction. J Neurosci, 23:622–31.
Psychoyos, D., Hungund, B., Cooper, T. and Finnell, R.H. (2008) A cannabinoid analogue of Delta9-tetrahydrocannabinol disrupts neural development in chick. Birth Defects Res B Dev Reprod Toxicol, 83:477–88.
Puighermanal, E., Marsicano, G., Busquets-Garcia, A., Lutz, B., Maldonado, R. and Ozaita, A. (2009) Cannabinoid modulation of hippocampal long-term memory is mediated by mTOR signaling. Nat Neurosci, 12:1152–8.
Rakhade, S.N. and Jensen, F.E. (2009) Epileptogenesis in the immature brain: emerging mechanisms. Nat Rev Neurol, 5:380–91.
Ramocki, M.B. and Zoghbi, H.Y. (2008) Failure of neuronal homeostasis results in common neuropsychiatric phenotypes. Nature, 455:912–18.
Rubio-Araiz, A., Arevalo-Martin, A., Gomez-Torres, O., et al. (2008) The endocannabinoid system modulates a transient TNF pathway that induces neural stem cell proliferation. Mol Cell Neurosci, 38:374–80.
Rueda, D., Navarro, B., Martinez-Serrano, A., Guzman, M. and Galve-Roperh, I. (2002) The endocannabinoid anandamide inhibits neuronal progenitor cell differentiation through attenuation of the Rap1/B-Raf/ERK pathway. J Biol Chem, 277:46645–50.
Salazar, M., Carracedo, A., Salanueva, I.J., et al. (2009) Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells. J Clin Invest, 119:1359–72.
Schneider, M. (2009) Cannabis use in pregnancy and early life and its consequences: animal models. Eur Arch Psychiatry Clin Neurosci, 259:383–93.
Sipe, J.C., Chiang, K., Gerber, A.L., Beutler, E. and Cravatt, B.F. (2002) A missense mutation in human fatty acid amide hydrolase associated with problem drug use. Proc Natl Acad Sci USA, 99:8394–9.
Solbrig, M.V. and Hermanowicz, N. (2008) Cannabinoid rescue of striatal progenitor cells in chronic Borna disease viral encephalitis in rats. J Neurovirol, 14:252–60.
Stella, N. (2009) Endocannabinoid signaling in microglial cells. Neuropharmacology, 56 Suppl 1:244–53.
Sun, X. and Dey, S.K. (2008) Aspects of endocannabinoid signaling in periimplantation biology. Mol Cell Endocrinol, 286:S3–11.
Trazzi, S., Steger, M., Mitrugno, V.M., Bartesaghi, R. and Ciani, E. (2010) CB1 cannabinoid receptors increase neuronal precursor proliferation through AKT/glycogen synthase kinase-3beta/beta-catenin signaling. J Biol Chem, 285:10098–109.
Vitalis, T., Laine, J., Simon, A., Roland, A., Leterrier, C. and Lenkei, Z. (2008) The type 1 cannabinoid receptor is highly expressed in embryonic cortical projection neurons and negatively regulates neurite growth in vitro. Eur J Neurosci, 28:1705–18.
Walker, D.J., Suetterlin, P., Reisenberg, M., Williams, G. and Doherty, P. (2010) Down-regulation of diacylglycerol lipase-alpha during neural stem cell differentiation: identification of elements that regulate transcription. J Neurosci Res, 88:735–45.
Wang, H., Xie, H., Guo, Y., et al. (2006) Fatty acid amide hydrolase deficiency limits early pregnancy events. J Clin Invest, 116:2122–31.
Wang, X., Dow-Edwards, D., Keller, E. and Hurd, Y.L. (2003) Preferential limbic expression of the cannabinoid receptor mRNA in the human fetal brain. Neuroscience, 118:681–94.
Watson, S., Chambers, D., Hobbs, C., Doherty, P. and Graham, A. (2008) The endocannabinoid receptor, CB1, is required for normal axonal growth and fasciculation. Mol Cell Neurosci, 38:89–97.
Williams, E.J., Walsh, F.S. and Doherty, P. (2003) The FGF receptor uses the endocannabinoid signaling system to couple to an axonal growth response. J Cell Biol, 160:481–6.
Wolf, S.A., Bick-Sander, A., Fabel, K., et al. (2010) Cannabinoid receptor CB1 mediates baseline and activity-induced survival of new neurons in adult hippocampal neurogenesis. Cell Commun Signal, 8:12.
Wu, C.S., Zhu, J., Wager-Miller, J., et al. (2010) Requirement of cannabinoid CB(1) receptors in cortical pyramidal neurons for appropriate development of corticothalamic and thalamocortical projections. Eur J Neurosci, 32:693–706.
Zhou, D. and Song, Z.H. (2001) CB1 cannabinoid receptor-mediated neurite remodeling in mouse neuroblastoma N1E-115 cells. J Neurosci Res, 65:346–53.
Zorina, Y., Iyengar, R. and Bromberg, K.D. (2010) Cannabinoid 1 receptor and interleukin-6 receptor together induce integration of protein kinase and transcription factor signaling to trigger neurite outgrowth. J Biol Chem, 285:1358–70.
Zurolo, E., Iyer, A.M., Spliet, W.G., et al. (2010) CB1 and CB2 cannabinoid receptor expression during development and in epileptogenic developmental pathologies. Neuroscience, 170:28–41.