SUMMARY NR3A is the only NMDA receptor (NMDAR) subunit that down-regulates sharply prior to the onset of sensitive periods for plasticity, yet the functional importance of this transient expression remains largely unknown. To investigate the possibility that removal/replacement of juvenile NR3A-containing NMDARs is involved in experience-driven synapse maturation, we used a reversible transgenic system that allowed persistent NR3A expression in the postnatal forebrain. We found that removal of NR3A is required to develop strong NMDAR currents, full expression of long-term synaptic plasticity, a mature synaptic organization characterized by more synapses and larger postsynaptic densities, and the ability to form long-term memories. Deficits associated with prolonged NR3A were reversible, as late-onset suppression of transgene expression rescued both the synaptic and memory impairments. Our results suggest that NR3A behaves as a molecular brake to prevent the premature strengthening and stabilization of excitatory synapses, and that NR3A removal might thereby initiate critical stages of synapse maturation during early postnatal neural development.

LÓ PEZ, ICIAR P., AMELIA MARTI, FERMIN I. MILAGRO, MARIA DE LOS ANGELES ZULET, MARIA JESUS MORENO-ALIAGA, J. ALFREDO MARTINEZ, AND CARLOS DE MIGUEL. DNA microarray analysis of genes differentially expressed in diet-induced (cafeteria) obese rats. Obes Res. 2003;11:188 -194. Objective: To better understand the molecular basis of dietary obesity, we examined adipose tissue genes differentially expressed in an obesity model using DNA microarray analysis. Research Methods and Procedures:We assessed the expression level of over 12,500 transcripts in epididymal fat pads from (cafeteria) obese and control rats with the aid of the array technology. Results: Cafeteria (obese) rats weighed 50% more and had 2.5-fold higher levels of epididymal fat and elevated levels of circulating leptin. Adipose genes differentially expressed in obese and control rats were categorized into five groups: macronutrient metabolism, transcription factors, hormone receptor and signal transduction, redox and stress proteins, and cellular cytoskeleton. Interestingly, the expression levels of a number of genes involved in lipid metabolism such as glycerol-3-phosphate dehydrogenase, stearoyl coenzyme A desaturase, together with the transcription factors implicated in adipocyte differentiation (CAAT/enhancer binding protein-␣ and peroxisome proliferator-activated receptor-␥), were significantly increased in obese animals compared with control. The most up-regulated transcripts were the ob (49.2-fold change) and the fatty acid-binding protein genes (15.7-fold change). In contrast, genes related to redox and stress protein were generally down-regulated in obese animals compared with the control. Discussion: Our study showed that in diet-induced obesity, the expression levels of some important genes implicated in lipid metabolism were up-regulated, whereas those related to redox and stress protein were down-regulated in obese animals compared with control. This pattern of gene expression may occur in human obesity cases after high-fat intake.

The putative presence of the cannabinoid receptor type 2 (CB(2)-R) in the central nervous system is still a matter of debate. Although first described in peripheral and immune tissues, evidence suggesting the existence of CB(2)-Rs in glial cells and even neurons has been made available more recently. By taking advantage of newly designed CB(2)-R mRNA riboprobes, we have demonstrated by in situ hybridization and PCR the existence of CB2-R transcripts in a variety of brain areas of the primate Macaca fascicularis, including the cerebral cortex and the hippocampus, as well as in the external and internal divisions of the globus pallidus, both pallidal segments showing the highest abundance of CB(2)-R transcripts. In this regard, the presence of the messenger coding CB(2)-Rs within the pallidal complex highlights their consideration as potential targets for the treatment of movement disorders of basal ganglia origin.