Nr4a1-eGFP Is a Marker of Striosome-Matrix Architecture, Development and Activity in the Extended Striatum

Transgenic mice expressing eGFP under population specific promoters are widely used in neuroscience to identify specific subsets of neurons in situ and as sensors of neuronal activity in vivo. Mice expressing eGFP from a bacterial artificial chromosome under the Nr4a1 promoter have high expression within the basal ganglia, particularly within the striosome compartments and striatal-like regions of the extended amygdala (bed nucleus of the stria terminalis, striatal fundus, central amygdaloid nucleus and intercalated cells). Grossly, eGFP expression is inverse to the matrix marker calbindin 28K and overlaps with mu-opioid receptor immunoreactivity in the striatum. This pattern of expression is similar to Drd1, but not Drd2, dopamine receptor driven eGFP expression in structures targeted by medium spiny neuron afferents. Striosomal expression is strong developmentally where Nr4a1-eGFP expression overlaps with Drd1, TrkB, tyrosine hydroxylase and phospho-ERK, but not phospho-CREB, immunoreactivity in “dopamine islands”. Exposure of adolescent mice to methylphenidate resulted in an increase in eGFP in both compartments in the dorsolateral striatum but eGFP expression remained brighter in the striosomes. To address the role of activity in Nr4a1-eGFP expression, primary striatal cultures were prepared from neonatal mice and treated with forskolin, BDNF, SKF-83822 or high extracellular potassium and eGFP was measured fluorometrically in lysates. eGFP was induced in both neurons and contaminating glia in response to forskolin but SKF-83822, brain derived neurotrophic factor and depolarization increased eGFP in neuronal-like cells selectively. High levels of eGFP were primarily associated with Drd1+ neurons in vitro detected by immunofluorescence; however ∼15% of the brightly expressing cells contained punctate met-enkephalin immunoreactivity. The Nr4a1-GFP mouse strain will be a useful model for examining the connectivity, physiology, activity and development of the striosome system

Permanence of molecular features of obesity in subcutaneous adipose tissue of ex-obese subjects

Objective:Bariatric surgery represents a powerful tool for morbid obesity treatment. However, after stabilization of weight loss that follows surgical interventions, ex-obese patients face the problem of residual tissues removal. Actually, it is unknown whether the characteristics of this residual subcutaneous adipose tissue (SAT) are 'restored' with regard to molecular and morphological features.Design:To clarify this issue, we compared the SAT gene expression profile of ex-obese patients (ExOB-SAT, mean body mass index (BMI): 27.2±1.3 kg m-2) with that of lean (normal weight, NW-SAT, mean BMI: 22.6±1.1 kg m-2), overweight (OW-SAT, BMI: 27.65±0.2 kg m-2) and obese patients, according to BMI classes (OB1-SAT: 30≥BMI≤34.9, OB2-SAT: 35≥BMI≤39.9, OB3-SAT: BMI≥40).Subjects and Methods:A total of 58 samples of SAT were collected during surgical interventions. Gene expression levels were assessed by microarrays and significant genes were validated by RT-qPCR. Adipocyte hypertrophy, inflammatory infiltration and fibrosis were assessed by morphological techniques.Results:Global gene expression in ExOB-SAT was closely related to gene expression of OB3-SAT by hierarchical clustering procedures, in spite of different BMI. Metallothioneins (MT1A and MT2A) were the key over-expressed genes in both groups. At morphologic level, adipocyte hypertrophy and inflammatory infiltration improved after weight loss in ExOB-SAT, despite a persistence of fibrosis.Conclusions:Taken together, these results demonstrate that SAT gene expression is not fully restored, even after an extensive and stable weight loss. The persistence of 'obesity molecular features' in ExOB-SAT suggests that the molecular signature of adipose tissue is not solely dependent on weight loss and may need longer time period to completely disappear. © 2013 Macmillan Publishers Limited

Immigration can Destabilize Tri-trophic Interactions: Implications for Conservation of Top Predators

Top predators often have large home ranges and thus are especially vulnerable to habitat loss and fragmentation. Increasing connectance among habitat patches is therefore a common conservation strategy, based in part on models showing that increased migration between subpopulations can reduce vulnerability arising from population isolation. Although three-dimensional models are appropriate for exploring consequences to top predators, the effects of immigration on tri-trophic interactions have rarely been considered. To explore the effects of immigration on the equilibrium abundances of top predators, we studied the effects of immigration in the three-dimensional Rosenzweig-MacArthur model. To investigate the stability of the top predator equilibrium, we used MATCONT to perform a bifurcation analysis. For some combinations of model parameters with low rates of top predator immigration, population trajectories spiral towards a stable focus. Holding other parameters constant, as immigration rate is increased, a supercritical Hopf bifurcation results in a stable limit cycle and thus top predator populations that cycle between high and low abundances. Furthermore, bistability arises as immigration of the intermediate predator is increased. In this case, top predators may exist at relatively low abundances while prey become extinct, or for other initial conditions, the relatively higher top predator abundance controls intermediate predators allowing for non-zero prey population abundance and increased diversity. Thus, our results reveal one of two outcomes when immigration is added to the model. First, over some range of top predator immigration rates, population abundance cycles between high and low values, making extinction from the trough of such cycles more likely than otherwise. Second, for relatively higher intermediate predator migration rates, top predators may exist at low values in a truncated system with impoverished diversity, again with extinction more likely