Induction of Reactive Astrocytosis and Prevention of Motoneuron Cell Death by the I(2)-imidazoline Receptor Ligand LSL 60101

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2000 Aug 22

PMID 10952664

Citations 4

Authors

A Casanovas

G Olmos

J Ribera

M A Boronat

J E Esquerda

J A Garcia-Sevilla

Affiliations

Soon will be listed here.

Abstract

I(2)-imidazoline receptors are mainly expressed on glial cells in the rat brain. This study was designed to test the effect of treatment with the I(2)-imidazoline selective receptor ligand LSL 60101 [2-(2-benzofuranyl)imidazole] on the morphology of astrocytes in the neonate and adult rat brain, and to explore the putative neuroprotective effects of this glial response. Short-term (3 days) or chronic (7-10 days) treatment with LSL 60101 (1 mg kg(-1), i.p. every 12 h) enhanced the area covered by astroglial cells in sections of facial motor nucleus from neonate rats processed for glial fibrillary acidic protein (GFAP) immunostaining. Facial motoneurons surrounded by positive glial cell processes were frequently observed in sections of LSL 60101-treated rats. A similar glial response was observed in the parietal cortex of adult rats after chronic (10 days) treatment with LSL 60101 (10 mg kg(-1), i.p. every 12 h). Western-blot detection of the specific astroglial glutamate transporter GLT-1, indicated increased immunoreactivity after LSL 60101 treatment in the pons of neonate and in the parietoccipital cortex of adult rats. In the facial motor nucleus of neonate rats, the glial response after LSL 60101 treatment was associated to a redistribution of the immunofluorescence of the basic fibroblast growth factor (FGF-2) from the perinuclear area of motoneurons to cover most of their cytoplasm, suggesting a translocation of this mitogenic and neurotrophic factor towards secretion pathways. The neuroprotective potential of the above effects of LSL 60101 treatment was tested after neonatal axotomy of facial motor nucleus. Treatment with LSL 60101 (1 mg kg(-1), i.p. every 12 h from day 0 to day 10 after birth) significantly reduced (38%) motoneuron death rate 7 days after facial nerve axotomy performed on day 3 after birth. It is concluded that treatment with the I(2)-imidazoline selective receptor ligand LSL 60101 provokes morphological/biochemical changes in astroglia that are neuroprotective after neonatal axotomy.

Citing Articles

Microarray Analysis Revealed Inflammatory Transcriptomic Changes after LSL60101 Treatment in 5XFAD Mice Model.

Vasilopoulou F, Escolano C, Pallas M, Grinan-Ferre C Genes (Basel). 2021; 12(9).

PMID: 34573297 PMC: 8468036. DOI: 10.3390/genes12091315.

I imidazoline receptor modulation protects aged SAMP8 mice against cognitive decline by suppressing the calcineurin pathway.

Vasilopoulou F, Grinan-Ferre C, Rodriguez-Arevalo S, Bagan A, Abas S, Escolano C Geroscience. 2020; 43(2):965-983.

PMID: 33128688 PMC: 8110656. DOI: 10.1007/s11357-020-00281-2.

Behavioral and Cognitive Improvement Induced by Novel Imidazoline I Receptor Ligands in Female SAMP8 Mice.

Grinan-Ferre C, Vasilopoulou F, Abas S, Rodriguez-Arevalo S, Bagan A, Sureda F Neurotherapeutics. 2018; 16(2):416-431.

PMID: 30460457 PMC: 6554384. DOI: 10.1007/s13311-018-00681-5.

Protein misfolding, amyotrophic lateral sclerosis and guanabenz: protocol for a phase II RCT with futility design (ProMISe trial).

Bella E, Tramacere I, Antonini G, Borghero G, Capasso M, Caponnetto C BMJ Open. 2017; 7(8):e015434.

PMID: 28801400 PMC: 5724081. DOI: 10.1136/bmjopen-2016-015434.

References

Bousquet P . Imidazoline receptors: from basic concepts to recent developments. J Cardiovasc Pharmacol. 1995; 26 Suppl 2:S1-6. View

Sendtner M, Holtmann B, Kolbeck R, Thoenen H, Barde Y . Brain-derived neurotrophic factor prevents the death of motoneurons in newborn rats after nerve section. Nature. 1992; 360(6406):757-9. DOI: 10.1038/360757a0. View

Ruggiero D, Regunathan S, Wang H, Milner T, Reis D . Immunocytochemical localization of an imidazoline receptor protein in the central nervous system. Brain Res. 1998; 780(2):270-93. DOI: 10.1016/s0006-8993(97)01203-1. View

Crews L, Wigston D . The dependence of motoneurons on their target muscle during postnatal development of the mouse. J Neurosci. 1990; 10(5):1643-53. PMC: 6570065. View

OCallaghan J, Jensen K . Enhanced expression of glial fibrillary acidic protein and the cupric silver degeneration reaction can be used as sensitive and early indicators of neurotoxicity. Neurotoxicology. 1992; 13(1):113-22. View

Pettmann B, Weibel M, Sensenbrenner M, Labourdette G . Purification of two astroglial growth factors from bovine brain. FEBS Lett. 1985; 189(1):102-8. DOI: 10.1016/0014-5793(85)80851-6. View

Greensmith L, Hasan H, Vrbova G . Nerve injury increases the susceptibility of motoneurons to N-methyl-D-aspartate-induced neurotoxicity in the developing rat. Neuroscience. 1994; 58(4):727-33. DOI: 10.1016/0306-4522(94)90450-2. View

Regunathan S, Feinstein D, Raasch W, Reis D . Agmatine (decarboxylated arginine) is synthesized and stored in astrocytes. Neuroreport. 1995; 6(14):1897-900. DOI: 10.1097/00001756-199510020-00018. View

Snider W, ELLIOTT J, Yan Q . Axotomy-induced neuronal death during development. J Neurobiol. 1992; 23(9):1231-46. DOI: 10.1002/neu.480230913. View

10.

Mentis G, Greensmith L, Vrbova G . Motoneurons destined to die are rescued by blocking N-methyl-D-aspartate receptors by MK-801. Neuroscience. 1993; 54(2):283-5. DOI: 10.1016/0306-4522(93)90253-c. View

11.

Delaney C, Brenner M, Messing A . Conditional ablation of cerebellar astrocytes in postnatal transgenic mice. J Neurosci. 1996; 16(21):6908-18. PMC: 6579279. View

12.

Gomez-Pinilla F, Lee J, Cotman C . Basic FGF in adult rat brain: cellular distribution and response to entorhinal lesion and fimbria-fornix transection. J Neurosci. 1992; 12(1):345-55. PMC: 6575703. View

13.

Mattson M, Lovell M, Furukawa K, Markesbery W . Neurotrophic factors attenuate glutamate-induced accumulation of peroxides, elevation of intracellular Ca2+ concentration, and neurotoxicity and increase antioxidant enzyme activities in hippocampal neurons. J Neurochem. 1995; 65(4):1740-51. DOI: 10.1046/j.1471-4159.1995.65041740.x. View

14.

French N . Alpha 2-adrenoceptors and I2 sites in the mammalian central nervous system. Pharmacol Ther. 1995; 68(2):175-208. DOI: 10.1016/0163-7258(95)02005-5. View

15.

Maiese K, Pek L, Berger S, Reis D . Reduction in focal cerebral ischemia by agents acting at imidazole receptors. J Cereb Blood Flow Metab. 1992; 12(1):53-63. DOI: 10.1038/jcbfm.1992.7. View

16.

Boronat M, Olmos G, Garcia-Sevilla J . Attenuation of tolerance to opioid-induced antinociception and protection against morphine-induced decrease of neurofilament proteins by idazoxan and other I2-imidazoline ligands. Br J Pharmacol. 1998; 125(1):175-85. PMC: 1565592. DOI: 10.1038/sj.bjp.0702031. View

17.

Conway E, Gundlach A, Craven J . Temporal changes in glial fibrillary acidic protein messenger RNA and [3H]PK11195 binding in relation to imidazoline-I2-receptor and alpha 2-adrenoceptor binding in the hippocampus following transient global forebrain ischaemia in the rat. Neuroscience. 1998; 82(3):805-17. DOI: 10.1016/s0306-4522(97)00321-7. View

18.

Yan Q, Matheson C, Lopez O . In vivo neurotrophic effects of GDNF on neonatal and adult facial motor neurons. Nature. 1995; 373(6512):341-4. DOI: 10.1038/373341a0. View

19.

Mattson M, Rychlik B . Glia protect hippocampal neurons against excitatory amino acid-induced degeneration: involvement of fibroblast growth factor. Int J Dev Neurosci. 1990; 8(4):399-415. DOI: 10.1016/0736-5748(90)90073-b. View

20.

Graeber M, Streit W, Kreutzberg G . Axotomy of the rat facial nerve leads to increased CR3 complement receptor expression by activated microglial cells. J Neurosci Res. 1988; 21(1):18-24. DOI: 10.1002/jnr.490210104. View