TRKB signalling controls the expression of N-methyl-d-aspartate receptors in the visual cortex.
NMDA receptors (NMDARs) are multimeric proteins, the biological and functional characteristics of which depend on differential subunit assembly during postnatal development. In the present paper, we investigated whether the expression of NMDAR subunits NR1, NR2A, NR2B is influenced by neurotrophins in rat visual cortex. We used a soluble form of the TrkB receptor engineered as an immunoadhesin (TrkB-IgG) in order to block TrkB ligands. TrkB-IgG was released through a cannula implanted in the occipital pole and connected to a mini-osmotic pump. TrkB-IgG was continuously released from postnatal day 20-21 (P20-21) to P36-37. In a different group of animals used as controls, osmotic pumps were filled with saline. Different antibodies were used to stain neurons expressing NR1, NR2A and NR2B. We counted the number of neurons stained for NR2A and NR2B subunits and expressed this as percentage with respect to the total number of cresyl-violet stained neurons in each cortical layer. In the visual cortex of TrkB-IgG-treated rats, the percentage of neurons expressing NR2A was significantly increased in all cortical layers. Concerning the NR2B subunit, the percentage of stained neurons was not significantly different between TrkB-IgG-treated and control rats. The staining level for both NR2A and NR2B, but not NR1, was reduced in all cortical layers in TrkB-IgG-treated animals. In agreement with this result, the endogenous levels of NR2A and NR2B subunits were reduced in TrkB-IgG-treated animals as shown by Western blotting. Thus, TrkB signalling controls the cellular expression of NMDAR subunits in visual cortical neurons during postnatal development.
Margotti
Elisa
E
Neuroscience Program, International School for Advanced Studies (S.I.S.S.A), via Beirut 2-4, 34014, Trieste, Italy.
Covaceuszach
Sonia
S
Tongiorgi
Enrico
E
Cattaneo
Antonino
A
Domenici
Luciano
L
D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D007074:Immunoglobulin G; D007150:Immunohistochemistry; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D014793:Visual Cortex / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*
D007074:Immunoglobulin G; C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D009414:Nerve Growth Factors; D016194:Receptors, N-Methyl-D-Aspartate; D011993:Recombinant Fusion Proteins; D020813:Receptor, trkB