AMPA/kainate receptors in mouse spinal cord cell-specific display of receptor subunits by oligodendrocytes and astrocytes and at the nodes of Ranvier

Author(s): Brand Schieber E, Werner P


Spinal cord white matter is susceptible to AMPA/kainate (KA)-type glutamate receptor-mediated excitotoxicity. To understand this vulnerability, it is important to characterize the distribution of AMPA/KA receptor subunits in this tissue. Using immunohistochemistry and laser confocal microscopy, we studied the expression sites of AMPA/KA receptor subunits in mouse spinal cord. The white matter showed consistent immunoreactivity for AMPA receptor subunit GluR2/3 and KA receptor subunits GluR6/7 and KA2. In contrast, antibodies against GluR1, GluR2, GluR4 (AMPA), and GluR5 (KA) subunits showed only weak and occasional labeling of white matter. However, gray matter neurons did express GluR1 and GluR2, as well as GluR2/3. The white matter astrocytes were GluR2/3 and GluR6/7 immunopositive, while the gray matter astrocytes displayed primarily GluR6/7. Both exclusively and abundantly, KA2 labeled oligodendrocytes and myelin, identified by CNPase expression. Interestingly, myelin basic protein, another myelin marker, showed less correlation with KA2 expression, placing KA2 at specific CNPase-containing subdomains. Focal points of dense KA2 labeling showed colocalization with limited, but distinct, axonal regions. These regions were identified as nodes of Ranvier by coexpressing the nodal marker, ankyrin G. Overall, axonal tracts showed little, if any, AMPA/KA receptor expression. The proximity of oligodendrocytic KA2 to the axonal node and the paucity of axonal AMPA/kainate receptor expression suggest that excitotoxic axonal damage may be secondary and, possibly, mediated by oligodendrocytes. Our data demonstrate differential expression of glutamate AMPA and KA receptor subunits in mouse spinal cord white matter and point to astrocytes and oligodendrocytes as potential targets for pharmacological intervention in white matter glutamate excitotoxicity. GLIA 42:12–24, 2003. © 2003 Wiley-Liss, Inc.

Similar Articles

Glia and pain is chronic pain a gliopathy? Pain 154: S10-S28

Author(s): Ji RR, Berta T, Nedergaard M

Astrocytes are active players in cerebral innate immunity

Author(s): Farina C, Aloisi F, Meinl E

Minocycline improves peripheral and autonomic neuropathy in type 2 diabetes: MIND study

Author(s): Syngle A, Verma I, Krishan P, Garg N, Syngle V, et al.

Clinical trial of the p38 MAP kinase inhibitor dilmapimod in neuropathic pain following nerve injury

Author(s): Anand P, Shenoy R, Palmer JE, Baines AJ, Lai RY, et al.

Evidence of central inflammation in fibromyalgia-increased cerebrospinal fluid interleukin-8 levels

Author(s): Kadetoff D, Lampa J, Westman M, Andersson M, Kosek E

Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome

Author(s): Russell IJ, Orr MD, Littman B, Vipraio GA, Alboukrek D, et al.

Pharmacological characterisation of acid-induced muscle allodynia in rats

Author(s): Nielsen AN, Mathiesen C, Blackburn-Munro G

Models of Muscle Pain: Carrageenan Model and Acidic Saline Model

Author(s): Radhakrishnan R, Bement MKH, Skyba D, Sluka KA, Kehl LJ, et al.

Changes in expression of NMDA-NR1 receptor subunits in the rostral ventromedial medulla modulate pain behaviors

Author(s): Da Silva LF, Walder RY, Davidson BL, Wilson SP, Sluka KA, et al.

Quantitative aspects of reactive gliosis: A review

Author(s): Norton WT, Aquino DA, Hozumi I, Chiu FC, Brosnan CF, et al.

Microglia-specific localisation of a novel calcium binding protein, Iba1

Author(s): Ito D, Imai Y, Ohsawa K, Nakajima K, Fukuuchi Y, et al.

Stress exacerbates neuropathic pain via glucocorticoid and NMDA receptor activation

Author(s): Alexander JK, DeVries AC, Kigerl KA, Dahlman JM, Popovich PG, et al.

Cytokine effects on glutamate uptake by human astrocytes

Author(s): Hu S, Sheng WS, Ehrlich LC, Peterson PK, Chao CC, et al.

Spinal glutamate uptake is critical for maintaining normal sensory transmission in rat spinal cord

Author(s): Liaw WJ, Stephens RL, Binns BC, Chu Y, Sepkuty JP, et al.

Astrocytes contain a vesicular compartment that is competent for regulated exocytosis of glutamate

Author(s): Bezzi P, Gundersen V, Galbete JL, Seifert G, Steinhauser C, et al.

Cytosolic calcium oscillations in astrocytes may regulate exocytotic release of glutamate

Author(s): Pasti L, Zonta M, Pozzan T, Vicini S, Carmignoto G, et al.

SNARE protein-dependent glutamate release from astrocytes

Author(s): Araque A, Li N, Doyle RT, Haydon PG

Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors

Author(s): Fellin T, Pascual O, Gobbo S, Pozzan T, Haydon PG, et al.

Glutamate-mediated astrocyte-neuron signalling

Author(s): Parpura V, Basarsky TA, Liu F, Jeftinija K, Jeftinija S, et al.

Repeated sound stress enhances inflammatory pain in the rat

Author(s): Khasar SG, Green PG, Levine JD

Evidence for brain glial activation in chronic pain patients

Author(s): Loggia ML, Chonde DB, Akeju O, Arabasz G, Catana C, et al.

Neuroinflammation of the spinal cord and nerve roots in chronic radicular pain patients

Author(s): Albrecht DS, Ahmed SU, Kettner NW, Borra RJ, Cohen Adad J, et al.

19F magnetic resonance imaging of endogenous macrophages in inflammation

Author(s): Temme S, Bonner F, Schrader J, Flogel U