NMDA receptor subunit expression in the supraoptic nucleus of adult rats: Dominance of NR2B and NR2D

Abstract

The supraoptic nucleus (SON) of the hypothalamus contains magnocellular neurosecretory neurons (MNC) which synthesize and release the peptide hormones vasopressin and oxytocin. Glutamate is a prominent excitatory neurotransmitter in the SON and regulates MNC excitability. NMDA receptors (NMDAR), a type of ionotropic glutamate receptor, mediate synaptic plasticity of MNCs and are necessary for characteristic burst firing patterns which serve to maximize hormone release. NMDARs are di- or tri-heteromeric complexes of NR1 and NR2 subunits. Receptor properties depend on NR2 subunit composition and variable splicing of NR1. We investigated the expression profile of NR1 and NR2 subunits in the SON at the mRNA and protein levels, plus protein expression of NR1 splice variants in control and salt-loaded adult rats. There was robust mRNA expression of all subunits, with NR2D levels being the highest. At the protein level, NR1, NR2B and NR2D were robustly expressed, while NR2A was weakly expressed. NR2C protein was not detected with either of two antibodies. All four NR1 splice variant cassettes (N1, C1, C2, C2’) were detected in the SON, though NR1 N1 expression was too low for accurate analysis. Three days of salt-loading did not alter mRNA, protein or splice variant expression of NMDAR subunits in the SON. Robust NR2D protein expression has not been previously shown in MNCs, and is uncommon in the adult brain. Though the functional significance of this unusual expression profile is unknown, it may contribute to important physiological characteristics of SON neurons, such as burst firing and resistance to excitotoxicity.

Brain-Derived Neurotrophic Factor-Tyrosine Kinase B Pathway Mediates NMDA Receptor NR2B Subunit Phosphorylation in the Supraoptic Nuclei Following Progressive Dehydration

“…Results from studies using chronic osmotic stimulation show NR1 up‐regulation and NR2B down‐regulation in homogenates obtained from SON and PVN (27, 60), suggesting that NR2B and NR1‐containing NMDA receptors are involved in the osmoregulatory functions of MNCs. No changes in the abundance of NR1 and NR2B were found in the present study, nor in another recent study that examined changes in NMDA receptor subunits after 3 days of salt loading (61). These differences could be related to the longer duration of the osmotic stimulation used in the earlier work (7–10 days), the additional physiological changes associated with WD or the antibodies used in the separate studies.…”

Molecular Mechanisms Elicited by d-Aspartate in Leydig Cells and Spermatogonia

“…Albeit d -Asp specific receptors have not yet been identified, a number of reports indicate that NMDAR has an affinity for d -Asp [ 23 , 24 , 25 , 26 ]. NMDAR is assembled as heterologous tetramers comprised of an obligatory GRIN1 subunit (more commonly known as NR1) plus four modulatory GRIN2 subunits (GRIN2A, GRIN2B, GRIN2C, GRIN2D; more commonly known as NR2A, NR2B, NR2C and NR2D, respectively), each encoded by a separate gene [ 27 ].…”

Interleukin-6 reduces NMDAR-mediated cytosolic Ca2+ overload and neuronal death via JAK/CaN signaling

“…Both NR1 and NR2 subunits are necessary to form functional glutamate-gated NMDARs in mammalian systems [4]. NR2 has been found to have the four isoforms, NR2A, NR2B, NR2C and NR2D, which are differentially expressed in different developmental stages of the central nervous system (CNS) and different brain regions [5,6]. NR2C is expressed in the cerebellum and highly expressed in cerebellar granule cell layer [6,7].…”