Prostaglandin E2 Regulates AMPA Receptor Phosphorylation and Promotes Membrane Insertion in Preoptic Area Neurons and Glia during Sexual Differentiation

Sexual differentiation of the rodent brain is dependent upon the organizing actions of the steroid hormone, estradiol. In the preoptic area, a brain region critical for the expression of adult reproductive behavior, there are twice as many dendritic spine synapses per unit length on newborn male neurons compared to female neurons and this sex difference correlates with the expression of adult male copulatory behavior. The sex difference in the POA is achieved via estradiol's upregulation of the membrane-derived lipid signaling molecule prostaglandin E2 (PGE2); PGE2 is necessary and sufficient to masculinize both dendritic spine density and adult sexual behavior in rats. We have previously shown that PGE2 activates EP2 and EP4 receptors which increases protein kinase A (PKA) activity and that masculinized dendritic spine density and sex behavior are both dependent upon PKA as well as activation of AMPA type glutamate receptors. In the current experiments, we build upon this signaling cascade by determining that PGE2 induces phosphorylation of the AMPA receptor subunit, GluR1, which leads to increased AMPA receptor insertion at the membrane. Treating female pups on the day of birth with PGE2 induced the phosphorylation of GluR1 at the PKA-sensitive site within 2 hours of treatment, an effect that was blocked by co-administration of the PKA/AKAP inhibitor, HT31 with PGE2. Brief treatment of mixed neuronal/glial POA cultures with PGE2 or the cAMP/PKA stimulator, forskolin, increased membrane associated GluR1 in both neurons and glia. We speculate that PGE2 induced increases in AMPA receptor associated with the membrane underlies our previously observed increase in dendritic spine density and is a critical component in the masculinization of rodent sex behavior

The subchondral bone in articular cartilage repair: current problems in the surgical management

As the understanding of interactions between articular cartilage and subchondral bone continues to evolve, increased attention is being directed at treatment options for the entire osteochondral unit, rather than focusing on the articular surface only. It is becoming apparent that without support from an intact subchondral bed, any treatment of the surface chondral lesion is likely to fail. This article reviews issues affecting the entire osteochondral unit, such as subchondral changes after marrow-stimulation techniques and meniscectomy or large osteochondral defects created by prosthetic resurfacing techniques. Also discussed are surgical techniques designed to address these issues, including the use of osteochondral allografts, autologous bone grafting, next generation cell-based implants, as well as strategies after failed subchondral repair and problems specific to the ankle joint. Lastly, since this area remains in constant evolution, the requirements for prospective studies needed to evaluate these emerging technologies will be reviewed

The formation of garnet in olivine-bearing metagabbros from the Adirondacks

A regional study of olivine-bearing metagabbros in the Adirondacks has permitted testing of the P(pressure)-T(temperature)-X(composition) dependence of garnet-forming reactions as well as providing additional regional metamorphic pressure data. Six phases, olivine, orthopyroxene, clinopyroxene, garnet, plagioclase and spinel, which can be related by the reactions: orthopyroxene+clinopyroxene+spinel +anorthite=garnet, and forsterite+anorthite=garnet occur together both in coronal and in equant textures indicative of equilibrium. Compositions of the respective minerals are typically Fo 25–72 , En 44–75 , En 30–44 Fs 9–23 Wo 47–49 , Pp 13–42 Alm 39–63 Gr 16–20 , An 29–49 and Sp 16–58 . When they occur in the same rock, equant and coronal garnets are homogeneous and compositionally identical suggesting that chemical equilibrium may have been attained despite coronal textures. Extrapolating reactions in the simple CMAS system to granulite temperatures and making thermodynamic corrections for solid solutions gives equilibration pressures (using the thermometry of Bohlen et al. 1980b) ranging from about 6.5 kb in the Lowlands and southern Adirondacks to 7.0–8.0 kb in the Highlands for the assemblage olivine-plagioclase-garnet. These results are consistent with inferred peak metamorphic conditions in the Adirondacks (Valley and Bohlen 1979; Bohlen and Boettcher 1981). Thus the isobaric retrograde path suggested by Whitney and McLelland (1973) and Whitney (1978) for the formation of coronal garnet in olivine metagabbros may not be required. Application of the same equilibria gives >8.7 kb for South Harris, Scotland and 0.9 kb for the Nain Complex. Disagreement of the latter value with orthopyroxeneolivine-quartz barometry (Bohlen and Boettcher 1981) suggests that the use of iron-rich rocks (olivines ≧Fa 50 ) results in errors in calculated pressures.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47335/1/410_2004_Article_BF00371301.pd