Evidence for a feeding related association between melanocortin in the NTS and Neuropeptide-Y in the PVN.

Melanocortin and neuropeptide-Y (NPY) are both involved in feeding and energy regulation, and they have opposite effects in the paraventricular nucleus of the hypothalamus (PVN). The present study examined an interaction between melanocortin in the nucleus of the solitary tract (NTS) and NPY in the PVN. Male Sprague-Dawley rats were implanted with cannulae in the injection sites of interest. In Experiment 1, subjects received either the melanocortin 3/4-receptor (MC3/4) antagonist SHU9119 (0, 10, 50 and 100 pmol/0.5 µl) or the MC3/4 agonist MTII (0, 10, 50, 100 and 200 pmol/0.5 µl) into the NTS. Food intake was measured at 1, 2, 4, 6 and 24-h post-injection. Administration of SHU9119 into the NTS significantly and dose-dependently increased food intake at 1, 2, 4, 6 and 6-24-h, and administration of MTII into the NTS significantly and dose-dependently decreased 24-h free feeding. In Experiment 2, subjects received the MC3/4 agonist MTII (0, 10, 50, 100 and 200 pmol/0.5 µl) into the NTS just prior to NPY (0 and 1µg/0.5 µl) in the PVN. PVN injection of NPY stimulated feeding, and administration of MTII (50, 100 and 200 pmol) into the NTS significantly and dose-dependently decreased NPY-induced feeding at 2, 4, 6 and 6-24-h. These data suggest that there could be a neuronal association between melanocortin in the NTS and NPY in the PVN, and that the melanocortin system in the NTS has an antagonistic effect on NPY-induced feeding in the PVN.

Narrowing the wingless-2 mutation to a 227 kb candidate region on chicken chromosome 12.

Wingless-2 (wg-2) is an autosomal recessive mutation in chicken that results in an embryonic lethal condition. Affected individuals exhibit a multisystem syndrome characterized by absent wings, truncated legs, and craniofacial, kidney, and feather malformations. Previously, work focused on phenotype description, establishing the autosomal recessive pattern of Mendelian inheritance and placing the mutation on an inbred genetic background to create the congenic line UCD Wingless-2.331. The research described in this paper employed the complementary tools of breeding, genetics, and genomics to map the chromosomal location of the mutation and successively narrow the size of the region for analysis of the causative element. Specifically, the wg-2 mutation was initially mapped to a 7 Mb region of chromosome 12 using an Illumina 3 K SNP array. Subsequent SNP genotyping and exon sequencing combined with analysis from improved genome assemblies narrowed the region of interest to a maximum size of 227 kb. Within this region, 3 validated and 3 predicted candidate genes are found, and these are described. The wg-2 mutation is a valuable resource to contribute to an improved understanding of the developmental pathways involved in chicken and avian limb development as well as serving as a model for human development, as the resulting syndrome shares features with human congenital disorders.

Effects of thyroxine treatment on histology and behavior using the methimazole model of congenital hypothyroidism in the rat.

The timing of thyroxine (T4) replacement treatment in congenital hypothyroidism (CH) has been suggested to be important for optimizing cognitive recovery in humans; however this has not been fully established using modern animal models of CH. Consequently, the current studies investigated the ameliorating effects of postnatal T4 treatment on neuropathology and behavior in CH rats. Rat dams were administered methimazole to produce CH offspring, then brain tissue from male CH pups was analyzed to determine the effects of postnatal (P3, P7, P14 and P21) T4 treatment on hippocampal dendritic branching and the expression of nerve growth factor (NGF). Two operant behavioral procedures were employed to confirm and extend previous findings obtained using this model, and to investigate timelines for instigating T4 treatment on improved behavioral outcomes. T4 treatment initiated at P14 was protective of a reduction in dendritic branching in the hippocampus, and initiated at P7 was protective of a reduction of NGF expression in the fimbria of the hippocampus. Induction of CH did not affect the acquisition of simple operant response rules but had a significant effect on the acquisition of complex operant rules subsequently imposed. Furthermore, T4 treatment initiated at P3 protected learning deficits seen following the imposition of complex operant response rules. These findings indicate T4 treatment initiated at P7 is sufficient for the protection of hippocampal NGF expression and dendritic branching but for the protection of complex behavioral abilities T4 treatment is necessary prior to or approximating P3.

Effect of intracerebroventricular injection of TiO2 nanoparticles on complex behaviour in the rat.

There are no data available on the behavioural effects of centrally administered nanoparticles in freely moving intact mammals. Consequently, in the current study male Sprague-Dawley rats were trained to respond under an alternating-lever cyclic-ratio (ALCR) schedule of food reinforcement. Under this schedule, ascending and descending sequences of fixed-ratio (FR) lever press requirements for food reinforcement were presented over six cycles, with each discrete FR component completed on the alternate lever to the previous component. The final version of the schedule was comprised of an ascending followed by a descending sequence of the ratio values 2, 6, 12, 20, 30, 42 and 56, repeated over six cycles. When the rats were able to complete this version of the ALCR schedule in 40 min, each was implanted with a permanently indwelling ICV cannula aimed at the lateral ventricle of the brain, and allowed to recover for 7 days. On the first day of the experiment, all rats were injected with either titanium dioxide (TiO2, 9 nm, stabilised with gallic acid, 10 microl volume, 2 mg/ml) nanoparticles, or 10 microl saline (control). Two-hours after the ICV injections, the behaviour of all rats was measured using the ALCR schedule, and their behaviour was also measured (no ICV injection) for the next 7 days. Under the ALCR schedule, the number of lever-switching errors and incorrect lever perseverations significantly increased in the TiO2 group (p < 0.05). Other parameters of the ALCR schedule (RRRs and PRPs), which indicate the induction of malaise or general motor retardation, were not altered following ICV TiO2 injection. The findings of the current study indicate that central administration of TiO2 nanoparticles induced behavioural deterioration in freely moving intact animals, that the induced behavioural deterioration was a result of central rather than peripheral outcomes, and that this effect was chronic rather than acute.

Aß oligomer toxicity inhibitor protects memory in models of synaptic toxicity.

BACKGROUND AND PURPOSE: Amyloid-ß (Aß) aggregation into synaptotoxic, prefibrillar oligomers is a major pathogenic event underlying the neuropathology of Alzheimer's disease (AD). The pharmacological and neuroprotective properties of a novel Aß aggregation inhibitor, SEN1269, were investigated on aggregation and cell viability and in test systems relevant to synaptic function and memory, using both synthetic Aß(1-42) and cell-derived Aß oligomers. EXPERIMENTAL APPROACH: Surface plasmon resonance studies measured binding of SEN1269 to Aß(1-42) . Thioflavin-T fluorescence and MTT assays were used to measure its ability to block Aß(1-42) -induced aggregation and reduction in cell viability. In vitro and in vivo long-term potentiation (LTP) experiments measured the effect of SEN1269 on deficits induced by synthetic Aß(1-42) and cell-derived Aß oligomers. Following i.c.v. administration of the latter, a complex (alternating-lever cyclic ratio) schedule of operant responding measured effects on memory in freely moving rats. KEY RESULTS: SEN1269 demonstrated direct binding to monomeric Aß(1-42) , produced a concentration-related blockade of Aß(1-42) aggregation and protected neuronal cell lines exposed to Aß(1-42) . In vitro, SEN1269 alleviated deficits in hippocampal LTP induced by Aß(1-42) and cell-derived Aß oligomers. In vivo, SEN1269 reduced the deficits in LTP and memory induced by i.c.v. administration of cell-derived Aß oligomers. CONCLUSIONS AND IMPLICATIONS: SEN1269 protected cells exposed to Aß(1-42) , displayed central activity with respect to reducing Aß-induced neurotoxicity and was neuroprotective in electrophysiological and behavioural models of memory relevant to Aß-induced neurodegeneration. It represents a promising lead for designing inhibitors of Aß-mediated synaptic toxicity as potential neuroprotective agents for treating AD.

Electrophysiological, pharmacological and molecular profile of the transient outward rectifying conductance in rat sympathetic preganglionic neurons in vitro.

Transient outward rectifying conductances or A-like conductances in sympathetic preganglionic neurons (SPN) are prolonged, lasting for hundreds of milliseconds to seconds and are thought to play a key role in the regulation of SPN firing frequency. Here, a multidisciplinary electrophysiological, pharmacological and molecular single-cell rt-PCR approach was used to investigate the kinetics, pharmacological profile and putative K+ channel subunits underlying the transient outward rectifying conductance expressed in SPN. SPN expressed a 4-aminopyridine (4-AP) sensitive transient outward rectification with significantly longer decay kinetics than reported for many other central neurons. The conductance and corresponding current in voltage-clamp conditions was also sensitive to the Kv4.2 and Kv4.3 blocker phrixotoxin-2 (1-10 µM) and the blocker of rapidly inactivating Kv channels, pandinotoxin-Kα (50 nM). The conductance and corresponding current was only weakly sensitive to the Kv1 channel blocker tityustoxin-Kα and insensitive to dendrotoxin I (200 nM) and the Kv3.4 channel blocker BDS-II (1 µM). Single-cell RT-PCR revealed mRNA expression for the α-subunits Kv4.1 and Kv4.3 in the majority and Kv1.5 in less than half of SPN. mRNA for accessory ß-subunits was detected for Kvß2 in all SPN with differential expression of mRNA for KChIP1, Kvß1 and Kvß3 and the peptidase homologue DPP6. These data together suggest that the transient outwardly rectifying conductance in SPN is mediated by members of the Kv4 subfamily (Kv4.1 and Kv4.3) in association with the ß-subunit Kvß2. Differential expression of the accessory ß subunits, which may act to modulate channel density and kinetics in SPN, may underlie the prolonged and variable time-course of this conductance in these neurons.

Effects of intrahippocampal NAC 61-95 injections on memory in the rat and attenuation with vitamin E.

Parkinson's disease (PD)-related dementia affects approximately 40% of PD patients and the severity of this dementia correlates significantly with the density of Lewy body (LB) deposition in the PD brain. Aggregated alpha-synuclein protein is the major component of LB's and the non-amyloid component (NAC) region of alpha-synuclein, residues 61-95, is essential for the aggregation and toxicity of this protein. The current study evaluated the effect of pre-aggregated NAC(61-95) injected into the CA3 area of the dorsal hippocampus of the brain on memory in the rat. Previous research has suggested that oxidative stress processes may play a role in the neuropathology of PD, therefore the effect of treatment with vitamin E, an antioxidant, was also evaluated. Male Sprague-Dawley rats were trained in two-lever operant chambers under an alternating-lever cyclic-ratio (ALCR) schedule of food reinforcement. When responding showed no trends, subjects were divided into four groups. Two groups were injected bilaterally into the dorsal hippocampus with aggregated NAC(61-95) (5 microl suspension), and two groups were injected bilaterally into the dorsal hippocampus with sterile water (5 microl). Subgroups were treated with either vitamin E (150 mg/kg in Soya oil) or vehicle (Soya oil) daily. Injection of NAC(61-95) induced memory deficits and vitamin E treatment alleviated these. In addition, NAC(61-95) injections induced activated astrocytes and chronic treatment with vitamin E reduced the numbers of activated astrocytes. These results suggest that aggregated NAC(61-95) and associated oxidative stress, may play a role in the pathogenesis of cognitive deficits seen in PD-induced dementia.

An operant determination of the behavioral mechanism of benzodiazepine enhancement of food intake.

RATIONALE: A recent review paper by Cooper (Appetite 44:133-150, 2005) has pointed out that a role for benzodiazepines as appetite stimulants has been largely overlooked. Cooper's review cited several studies that suggested the putative mechanism of enhancement of food intake after benzodiazepine administration might involve increasing the perceived pleasantness of food (palatability). OBJECTIVES: The present study examined the behavioral mechanism of increased food intake after benzodiazepine administration. MATERIALS AND METHODS: The cyclic-ratio operant schedule has been proposed as a useful behavioral assay for differentiating palatability from regulatory effects on food intake (Ettinger and Staddon, Physiol Behav 29:455-458, 1982 and Behav Neurosci 97:639-653, 1983). The current study employed the cyclic-ratio schedule to determine whether the effects on food intake of chlordiazepoxide (CDP) (5.0 mg/kg), sodium pentobarbital (5.0 mg/kg), and picrotoxin (1.0 mg/kg) were mediated through palatability or regulatory processes. RESULTS: The results of this study show that both the benzodiazepine CDP and the barbiturate sodium pentobarbital increased food intake in a manner similar to increasing the palatability of the ingestant, and picrotoxin decreased food intake in a manner similar to decreasing the palatability of the ingestant. CONCLUSIONS: These results suggest that the food intake enhancement properties of benzodiazepines are mediated through a mechanism affecting perceived palatability.

Chronic intracerebroventricular infusion of lipopolysaccharide: effects of ibuprofen treatment and behavioural and histopathological correlates.

Twenty male Wistar rats were trained under an alternating-lever cyclic-ratio (ALCR) schedule of food reinforcement. When responding showed no trends, each subject was subcutaneously implanted with an Alzet osmotic mini-pump, connected to a chronic indwelling cannula extending into the lateral ventricle of the brain. The mini-pumps were primed to infuse 0.25 microl lipopolysaccharide (LPS) (1.0 microg/0.25 ml) or 0.25 microl artificial cerebrospinal fluid (aCSF) per hour and were implanted for 28 days. LPS infusion produced behavioural deficits which chronic ibuprofen treatment (40 mg/kg every 12 h) alleviated. Infusion of LPS induced R 1282-positive amyloid deposits, and activation of microglia and astrocytes. Ibuprofen treatment reduced the numbers of activated microglia, and withdrawal of ibuprofen resulted in an increase in activated microglia; however, ibuprofen treatment had no effect on numbers of activated astrocytes in the LPS-infused subjects.

Parenteral antioxidant treatment preserves temporal discrimination following intrahippocampal aggregated Abeta(1-42) injections.

There is evidence that oxidative stress may play a role in the neuropathology of Alzheimer's disease (AD). This study used an aggregated beta-amyloid (Abeta) injection model of AD in the rat, and a recycling conjunctive schedule of food reinforcement to examine the effects of bilateral intrahippocampal injections of aggregated Abeta(1-42) (5.0 microl/side) on temporal discrimination, and the efficacy of the antioxidant alpha-tocopherol (150 mg/kg daily p.o.) in alleviating these effects. The results indicated that bilateral intrahippocampal injections of aggregated Abeta(1-42) detrimentally affected temporal discrimination from five-day block 31-35 post-injections until the end of the study (90 days post-injections). Daily treatment with alpha-tocopherol improved temporal discrimination under the recycling conjunctive schedule following aggregated Abeta(1-42) injections from the five-day block 61-65 days until the end of the study.

Granisetron attenuates exercise-induced conditioned taste aversion in the rat.

A conditioned taste aversion (CTA) paradigm was used in the present study to investigate whether CTA produced by exercise could be attenuated by the 5-HT(3) receptor antagonist granisetron. Male Sprague-Dawley rats were randomly allocated to one of four groups (Ns=6) and were exposed to salty (0.128 M sodium chloride) or sour (0.00138M citric acid) solutions. Subjects were injected with either saline solution (1.0 ml, 0.9%) or granisetron (0.5mg/kg, IP) and were exposed to 30 min of forced wheel running exercise (70 revolutions/30min) 10 min after injection. Exercise induced CTA to both the salty (3.7 ml intake) and sour-flaroured (3.1ml intake) solutions as compared with no exercise (intake 14.0 and 13.7 ml), and administration of granisetron significantly attenuated the exercise-induced CTA to the salty- and sour-flavoured solutions.

Behavioral and neurochemical mechanisms of the action of mild stress in the enhancement of feeding.

Rats were trained to respond under a cyclic-ratio schedule of reinforcement composed of an ascending, followed by a descending, sequence of ratio values. Subjects were trained while exposed to 70 dB white noise, then tested while exposed to 70 or 90 dB white noise. Exposure to 90 dB white noise elevated the response function (p<.02). Naloxone was then administered intraperitoneally at 0.3. 1.0. and 3.0 mg/kg under 70 dB and 90 dB white noise. Naloxone administration (1.0 and 3.0 mg/kg) significantly depressed the response function obtained under 90 dB white noise (ps<.01) but did not affect the function obtained under 70 dB white noise. These findings suggest that mild stress increases food intake through a mechanism affecting palatability enhanced by the release of endogenous opioids.

Genomic analysis of immediate/early response to shear stress in human coronary artery endothelial cells.

The involvement of shear stress in the pathogenesis of vascular disease has motivated efforts to define the endothelial cell response to applied shear stress in vitro. A central question has been the mechanisms by which endothelial cells perceive and respond to changes in fluid flow. We have utilized cDNA microarrays to characterize the immediate/early genomic response to applied laminar shear stress (LSS) in primary cultures of human coronary artery endothelial cells (HCAECs). Cells were exposed, in a parallel plate flow chamber, to 0, 15, or 45 dyn/cm2 LSS for 1 h, and gene expression profiles were determined using human GEM1 cDNA microarrays. We find that a high proportion of LSS-responsive genes are transcription factors, and these are related by their involvement in growth arrest. These likely play a central role in the reprogramming of endothelial homeostasis following the switch from a static to a shear-stressed environment. LSS-responsive genes were also found to encode factors involved in vasoreactivity, signal transduction, antioxidants, cell cycle-associated genes, and markers of cytoskeletal function and dynamics.

Behavioural and histopathological analyses of ibuprofen treatment on the effect of aggregated Abeta(1-42) injections in the rat.

It has been suggested that inflammatory processes may play a role in the development of Alzheimer's disease (AD), and that nonsteroidal anti-inflammatory drug treatments may provide protection against the onset of AD. In the current study male Wistar rats were trained in two-lever operant chambers under an alternating lever cyclic-ratio ratio (ALCR) schedule. When responding showed no trends, subjects were divided into groups. One group was bilaterally injected into the CA3 area of the hippocampus with 5 microl of aggregated beta-amyloid (Abeta) suspension, and one group was bilaterally injected into the CA3 area of the hippocampus with 5 microl of sterile saline. Subgroups were treated twice daily with 0.1 ml (40 mg/kg) ibuprofen administered orally. The results indicated that chronic administration of ibuprofen protected against detrimental behavioural effects following aggregated Abeta injections. Withdrawal of ibuprofen treatment from aggregated Abeta-injected subjects produced a decline in behavioural performance to the level of the non-treated aggregated Abeta-injected group. Ibuprofen treatment reduced the numbers of reactive astrocytes following aggregated Abeta injection, and withdrawal of ibuprofen resulted in an increase of reactive astrocytes. These results suggest that induced inflammatory processes may play a role in AD, and that ibuprofen treatment may protect against some of the symptoms seen in AD.

Amyloid beta-peptide1-40 increases neuronal membrane fluidity: role of cholesterol and brain region.

There is increasing evidence of an interaction between cholesterol dynamics and Alzheimer's disease (AD), and amyloid beta-peptide may play an important role in this interaction. Abeta destabilizes brain membranes and this action of Abeta may be dependent on the amount of membrane cholesterol. We tested this hypothesis by examining effects of Abeta1-40 on the annular fluidity (i.e., lipid environment adjacent to proteins) and bulk fluidity of rat synaptic plasma membranes (SPM) of the cerebral cortex, cerebellum, and hippocampus using the fluorescent probe pyrene and energy transfer. Amounts of cholesterol and phospholipid of SPM from each brain region were determined. SPM of the cerebellum were significantly more fluid as compared with SPM of the cerebral cortex and hippocampus. Abeta significantly increased (P < or = 0.01) annular and bulk fluidity in SPM of cerebral cortex and hippocampus. In contrast, Abeta had no effect on annular fluidity and bulk fluidity of SPM of cerebellum. The amounts of cholesterol in SPM of cerebral cortex and hippocampus were significantly higher (P < or = 0.05) than amount of cholesterol in SPM of cerebellum. There was significantly less (P < or = 0.05) total phospholipid in cerebellar SPM as compared with SPM of cerebral cortex. Neuronal membranes enriched in cholesterol may promote accumulation of Abeta by hydrophobic interaction, and such an interpretation is consistent with recent studies showing that soluble Abeta can act as a seed for fibrillogenesis in the presence of cholesterol.

Identification of central sites involved in butorphanol-induced feeding in rats.

Butorphanol (BT), a mixed kappa- and mu-opioid receptor agonist, induces vigorous food intake in rats. Peripheral injection of BT seems to increase food intake more effectively than intracerebroventricular administration. To further elucidate the nature of BT's influence on consummatory behavior, we examined which feeding-related brain areas exhibit increased c-Fos immunoreactivity (IR) following subcutaneous injection of 4 mg/kg body weight BT, a dose known to induce a maximal orexigenic response. We also evaluated whether direct administration of BT into the forebrain regions activated by peripheral BT injection affects food intake. Peripheral BT administration induced c-Fos-IR in the hypothalamic paraventricular nucleus (PVN), central nucleus of the amygdala (CeA), and nucleus of the solitary tract (NTS). However, 0.1-30 microg BT infused into the CeA, failed to increase food intake 1, 2, and 4 h after injection. Only the highest dose of BT (30 microg) injected into the PVN increased feeding. These results suggest that the PVN, CeA, and NTS mediate the effects of peripherally-injected BT. The PVN or CeA are probably not the main target sites of immediate BT action.

Molecular anatomy of an intracranial aneurysm: coordinated expression of genes involved in wound healing and tissue remodeling.

BACKGROUND AND PURPOSE: Approximately 6% of human beings harbor an unruptured intracranial aneurysm. Each year in the United States, >30 000 people suffer a ruptured intracranial aneurysm, resulting in subarachnoid hemorrhage. Despite the high incidence and catastrophic consequences of a ruptured intracranial aneurysm and the fact that there is considerable evidence that predisposition to intracranial aneurysm has a strong genetic component, very little is understood with regard to the pathology and pathogenesis of this disease. METHODS: To begin characterizing the molecular pathology of intracranial aneurysm, we used a global gene expression analysis approach (SAGE-Lite) in combination with a novel data-mining approach to perform a high-resolution transcript analysis of a single intracranial aneurysm, obtained from a 3-year-old girl. RESULTS: SAGE-Lite provides a detailed molecular snapshot of a single intracranial aneurysm. These data suggest that, at least in this specific case, aneurysmal dilation results in a highly dynamic cellular environment in which extensive wound healing and tissue/extracellular matrix remodeling are taking place. Specifically, we observed significant overexpression of genes encoding extracellular matrix components (eg, COL3A1, COL1A1, COL1A2, COL6A1, COL6A2, elastin) and genes involved in extracellular matrix turnover (TIMP-3, OSF-2), cell adhesion and antiadhesion (SPARC, hevin), cytokinesis (PNUTL2), and cell migration (tetraspanin-5). CONCLUSIONS: Although these are preliminary data, representing analysis of only one individual, we present a unique first insight into the molecular basis of aneurysmal disease and define numerous candidate markers for future biochemical, physiological, and genetic studies of intracranial aneurysm. Products of these genes will be the focus of future studies in wider sample sets.

Oxidation of polychlorinated benzenes by genetically engineered CYP101 (cytochrome P450(cam)).

Polychlorinated benzenes are recalcitrant environmental pollutants primarily because they are resistant to attack by dioxygenases commonly used by micro-organisms for the biodegradation of aromatic compounds. We have investigated the oxidation of polychlorinated benzenes by mutants of the haem mono-oxygenase CYP101 (cytochrome P450(cam)) from Pseudomonas putida with the aim of generating novel systems for their biodegradation. Wild-type CYP101 had low activity for the oxidation of dichlorobenzenes and trichlorobenzenes to the chlorophenols, but no products were detected for the heavily chlorinated benzenes. Increasing the active-site hydrophobicity with the Y96F mutation increased the activity up to 100-fold, and both pentachlorobenzene and hexachlorobenzene were oxidized slowly to pentachlorophenol. Decreasing the space available at the top of the active site with the F87W mutation to force the substrate to be bound closer to the haem resulted in a further 10-fold increase in activity with most substrates. Introducing the F98W mutation, also at the top of the active site, decreased the NADH-turnover rates but increased the coupling efficiencies, and > 90% coupling was observed for 1,3-dichlorobenzene and 1,3,5-trichlorobenzene with the F87W--Y96F--F98W mutant. The V247L mutation generally increased the NADH-turnover rates, and the F87W--Y96F--V247L mutant showed reasonably fast NADH turnover (229 min(-1)) with the highly insoluble pentachlorobenzene without the need for surfactants or organic cosolvents. As all chlorophenols are degraded by micro-organisms, novel biodegradation systems could be constructed in which CYP101 mutants convert the inert polychlorinated benzenes to the phenols, which are then readily degraded by natural pathways.

Maternal depression and parenting behavior: a meta-analytic review.

The results of 46 observational studies were analyzed to assess the strength of the association between depression and parenting behavior and to identify variables that moderated the effects. The association between depression and parenting was manifest most strongly for negative maternal behavior and was evident to a somewhat lesser degree in disengagement from the child. The association between depression and positive maternal behavior was relatively weak, albeit significant. Effects for negative maternal behavior were moderated by timing of the depression: Current depression was associated with the largest effects. However, residual effects of prior depression were apparent for all behaviors. Socioeconomic status, child age, and methodological variables moderated the effects for positive behavior: Effects were strongest for studies of disadvantaged women and mothers of infants. Studies using diagnostic interviews and self-report measures yielded similar effects, suggesting that deficits are not specific to depressive disorder. Research is needed to identify factors that affect the magnitude of parenting deficits among women who are experiencing depression and other psychological difficulties.

ARC POMC mRNA and PVN alpha-MSH are lower in obese relative to lean zucker rats.

Effects of obesity on gene expression for opioid peptides and neuropeptide-Y (NPY) in the arcuate nucleus (ARC), and on opioid peptides and alpha-melanocyte stimulating hormone (alpha-MSH) in the paraventricular nucleus (PVN) were examined in obese Zucker rats (18 weeks old). Obese Zucker rats are insulin-resistant, diabetic and hyperleptinemic as indicated by high serum glucose, insulin and leptin levels. ARC proOpiomelanocortin (POMC) mRNA levels were significantly lower in the obese relative to lean Zucker rats and ARC proNeuropeptide Y (proNPY) mRNA levels were higher (P<0.05). There were no differences in proDynorphin and proEnkephalin mRNA levels in the ARC (0.05). Obese Zucker rats had lower alpha-MSH and dynorphin A(1-17) peptide levels in the paraventricular nucleus (PVN) (P<0.05), but did not have lower PVN beta-endorphin peptide levels (0.05). The decrease in POMC in the ARC and decrease in alpha-MSH in the PVN seen in the obese Zucker rat in the present study suggest that reduced activity of the melanocortin system in the ARC to PVN pathway may contribute to the related hyperphagia. Reduced activity of the melanocortin system in the ARC to PVN pathway may be due to a disturbance of leptin signaling coupling to POMC.