Transcriptome Sequencing of Gene Expression in the Brain of the HIV-1 Transgenic Rat.

Transcriptome Sequencing of Gene Expression in the Brain of the HIV-1 Transgenic Rat.

PLoS One. 2013; 8(3): e59582
Li MD, Cao J, Wang S, Wang J, Sarkar S, Vigorito M, Ma JZ, Chang SL

The noninfectious HIV-1 transgenic (HIV-1Tg) rat was developed as a model of AIDs-related pathology and immune dysfunction by manipulation of a noninfectious HIV-1(gag-pol) virus with a deleted 3-kb SphI-MscI fragment containing the 3′ -region of gag and the 5′ region of pol into F344 rats. Our previous studies revealed significant behavioral differences between HIV-1Tg and F344 control rats in their performance in the Morris water maze and responses to psychostimulants. However, the molecular mechanisms underlying these behavioral differences remain largely unknown. The primary goal of this study was to identify differentially expressed genes and enriched pathways affected by the gag-pol-deleted HIV-1 genome. Using RNA deep sequencing, we sequenced RNA transcripts in the prefrontal cortex, hippocampus, and striatum of HIV-1Tg and F344 rats. A total of 72 RNA samples were analyzed (i.e., 12 animals per group × 2 strains × 3 brain regions). Following deep-sequencing analysis of 50-bp paired-end reads of RNA-Seq, we used Bowtie/Tophat/Cufflinks suites to align these reads into transcripts based on the Rn4 rat reference genome and to measure the relative abundance of each transcript. Statistical analyses on each brain region in the two strains revealed that immune response- and neurotransmission-related pathways were altered in the HIV-1Tg rats, with brain region differences. Other neuronal survival-related pathways, including those encoding myelin proteins, growth factors, and translation regulators, were altered in the HIV-1Tg rats in a brain region-dependent manner. This study is the first deep-sequencing analysis of RNA transcripts associated the HIV-1Tg rat. Considering the functions of the pathways and brain regions examined in this study, our findings of abnormal gene expression patterns in HIV-1Tg rats suggest mechanisms underlying the deficits in learning and memory and vulnerability to drug addiction and other psychiatric disorders observed in HIV-positive patients. HubMed – addiction


Psychometric Properties, Norms, and Factor Structure of the Diabetes Eating Problem Survey-Revised in a Large Sample of Children and Adolescents With Type 1 Diabetes.

Diabetes Care. 2013 Mar 27;
Wisting L, Frøisland DH, Skrivarhaug T, Dahl-Jørgensen K, Rø O

OBJECTIVEThe purpose of this study was to examine the psychometric properties of the Diabetes Eating Problem Survey-Revised (DEPS-R) in a large sample of young patients with type 1 diabetes, to establish norms, and to validate it against the Eating Attitudes Test-12 (EAT-12).RESEARCH DESIGN AND METHODSA total of 770 children and adolescents aged 11-19 years with type 1 diabetes completed the DEPS-R and the EAT-12. In addition, age- and sex-standardized BMI and HbA1c data were obtained from the Norwegian Childhood Diabetes Registry. In addition to tests of validity, principal axis factoring was conducted to investigate the factor structure of the 16-item DEPS-R.RESULTSThe DEPS-R demonstrated satisfactory Cronbach ? (0.89) and was significantly correlated with the EAT-12 (0.65; P < 0.01), indicating convergent validity. The mean (SD) DEPS-R scores were 11.0 (10.7) for the total sample and 7.7 (7.4) and 14.2 (2.4) for males and females, respectively.CONCLUSIONSThis study replicates and extends previous research demonstrating the psychometric properties of the abbreviated 16-item DEPS-R. Findings support the utility of this important screening tool to identify disturbed eating in young patients with type 1 diabetes. HubMed – addiction


Conditioned contribution of peripheral cocaine actions to cocaine reward and cocaine-seeking.

Neuropsychopharmacology. 2013 Mar 27;
Wang B, You ZB, Oleson EB, Cheer JF, Myal S, Wise RA

Cocaine has actions in the peripheral nervous system that reliably precede-and thus predict-its soon-to-follow central rewarding effects. In cocaine-experienced animals, the peripheral cocaine signal is relayed to the central nervous system, triggering excitatory input to the ventral tegmental origin of the mesocorticolimbic dopamine system, the system that mediates the rewarding effects of the drug. We used cocaine methiodide, a cocaine analogue that does not cross the blood-brain barrier, to isolate the peripheral actions of cocaine and determine their central and behavioral effects in animals first trained to lever-press for cocaine hydrochloride (the centrally acting and abused form of the drug). We first confirmed with fast-scan cyclic voltammetry that cocaine methiodide causes rapid dopamine release from dopamine terminals in cocaine hydrochloride-trained rats. We then compared the ability of cocaine hydrochloride and cocaine methiodide to establish conditioned place preferences in rats with self-administration experience. While cocaine hydrochloride established stronger place preferences, cocaine methiodide was also effective and its effectiveness increased (incubated) over weeks of cocaine abstinence. Cocaine self-administration was extinguished when cocaine methiodide or saline was substituted for cocaine hydrochloride in the intravenous self-administration paradigm, but cocaine hydrochloride and cocaine methiodide each reinstated non-rewarded lever-pressing after extinction. Rats extinguished by cocaine methiodide substitution showed weaker cocaine-induced reinstatement than rats extinguished by saline substitution. These findings suggest that the conditioned peripheral effects of cocaine can contribute significantly to cocaine-induced (but not stress-induced) cocaine craving, and suggest the cocaine cue as an important target for cue-exposure therapies for cocaine addiction.Neuropsychopharmacology accepted article preview online, 27 March 2013; doi:10.1038/npp.2013.75. HubMed – addiction