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R J Nelson

Publications and source records attributed to R J Nelson.

At least 73 records · Page 4Linked to original sources
PubMed1999

Elimination of aggressive behavior in male mice lacking endothelial nitric oxide synthase.

Male mice with targeted deletion of the gene encoding the neuronal isoform of nitric oxide synthase (nNOS(-/-)) display increased aggressive behavior compared with wild-type (WT) mice. Specific pharmacological inhibition of nNOS with 7-nitroindazole also augments aggressive behavior. We report here that male mice with targeted deletion of the gene encoding endothelial NOS (eNOS(-/-)) display dramatic reductions in aggression. The effects are selective, because an extensive battery of behavioral tests reveals no other deficits. In the resident-intruder model of aggression, resident eNOS(-/-) males show virtually no aggression. Latency for aggression onset is 25-30 times longer in eNOS(-/-) males compared with WT males in the rare instances of aggressive behaviors. Similarly, a striking lack of aggression is noted in tests of aggression among groups of four mice monitored in neutral cages. Although eNOS(-/-) mice are hypertensive ( approximately 14 mmHg blood pressure elevation), hypertension does not appear responsible for the diminished aggression. Reduction of hypertension with hydralazine does not change the prevalence of aggression in eNOS(-/-) mice. Extensive examination of brains from eNOS(-/-) male mice reveals no obvious neural damage from chronic hypertension. In situ hybridization in WT animals reveals eNOS mRNA in the brain associated exclusively with blood vessels and no neuronal localizations. Accordingly, vascular eNOS in the brain appears capable of influencing behavior with considerable selectivity.

Aggression↗
PubMed1999

Maternal aggression is reduced in neuronal nitric oxide synthase-deficient mice.

Lactating females express rapid extremes in behavior, ranging from gentle nurturance toward offspring to fiercely protective aggression against intruders. Although males often behave aggressively against intruders, female rodents usually express aggression only when rearing and protecting pups. Nitric oxide (NO) inhibits male aggression; however, its role in maternal aggression is unknown. In the present study, female mice with targeted disruption of the neuronal nitric oxide synthase gene (nNOS-/-) displayed significant deficits in maternal aggression relative to wild-type (WT) mice in terms of percentage displaying aggression, the average number of attacks against a male intruder, and the total time spent attacking the male intruder. The nNOS-/- mice displayed normal pup retrieval behavior. Because the specific deficits in maternal aggression in the nNOS-/- mice suggested a possible role for NO in maternal aggression, we combined behavioral testing of WT mice with immunohistochemistry for citrulline, an indirect marker of NO synthesis, to examine indirectly NO synthesis during maternal aggression. A significant increase in the number of citrulline-positive cells was identified in the medial preoptic nucleus, the suprachiasmatic nucleus, and the subparaventricular zone regions of the hypothalamus in aggressive lactating females relative to control mice. In other regions of the brain, no changes in the number of citrulline-positive cells were observed across either groups or treatments. These results provide two indirect lines of evidence that NO release is associated with maternal aggression.

Aggression↗
PubMed1999

Effects of photoperiod and reproductive responsiveness on pituitary sensitivity to GnRH in male prairie voles (Microtus ochrogaster).

In order to promote survival and reproductive success, many nontropical rodents inhibit reproduction well in advance of winter in response to decreasing day lengths. Male prairie voles (Microtus ochrogaster), small temperate zone rodents, vary in their reproductive response to photoperiod. Some male voles undergo complete gonadal regression when housed in short days (responders) whereas others fail to inhibit reproduction when exposed to short (i. e., <12 h light/day) day lengths (nonresponders). Previous research has shown that phenotypic variation in reproductive response is reflected at the level of the hypothalamic gonadotropin-releasing hormone (GnRH) neuronal system. The present study sought to determine if photoperiod or reproductive condition alters pituitary responsiveness to a GnRH challenge. Animals were housed in either long (LD 16:8) or short (LD 8:16) photoperiods for 10 weeks. Subsequently, short-day voles were separated into responders and nonresponders based on testicular size. To reduce the influence of endogenous testosterone on luteinizing hormone concentrations, half of the animals in each group were castrated. All animals were injected (i.p.) with either 100 or 50 ng of GnRH and a blood sample was collected after 15 min. Although castration resulted in a significant increase in LH concentrations (P < 0.05), neither photoperiod nor reproductive condition affected LH concentrations in response to a GnRH challenge (P > 0.05). Taken together, these data support the hypothesis that short photoperiods lead to reproductive inhibition by acting at the level of the hypothalamus rather than the pituitary.

Animals↗
PubMed1999

Reproductive function in female mice lacking the gene for endothelial nitric oxide synthase.

Nitric oxide (NO) acts as a neuronal messenger in both the central and peripheral nervous systems and has been implicated in reproductive physiology and behavior. Pharmacological inhibition of nitric oxide synthase (NOS) with the nonspecific NOS inhibitor, l-N(G)-nitro-Arg-methyl ester (l-NAME), induced deficits in both the number of ovarian rupture sites and the number of oocytes recovered in the oviducts of mice. Female neuronal NOS knockout (nNOS-/-) mice have normal numbers of rupture sites, but reduced numbers of oocytes recovered following systemic injections of gonadotropins, suggesting that NO produced by nNOS accounts, in part, for deficits in ovulatory efficiency observed after l-NAME administration. Additionally, endothelial NOS knockout (eNOS-/-) mice have reduced numbers of ovulated oocytes after superovulation. Because endothelial NOS has been identified in ovarian follicles, and because of the noted reduced breeding efficiency of eNOS-/- mice, the present study sought to determine the role of NO from eNOS in mediating the number of rupture sites present after ovulation. Estrous cycle length and variability were consistently reduced in eNOS-/- females. The number of rupture sites was normal in eNOS-/- mice under natural conditions and after administration of exogenous GnRH. After exogenous gonadotropin administration, eNOS-/- females displayed a significant reduction in the number of ovarian rupture sites. Female eNOS-/- mice also produced fewer pups/litter compared to WT mice. These data suggest that NO from endothelial sources might play a role in mediating rodent ovulation and may be involved in regulation of the timing of the estrous cycle.

Animals↗
PubMed1999

Elevated Fos-like immunoreactivity in the brains of postpartum female prairie voles, Microtus ochrogaster.

This study investigated the expression of the protein product of the immediate early gene c-fos in the brains of female prairie voles (Microtus ochrogaster) in association with pregnancy and postparturient activities including maternal behavior, lactation and postpartum estrus. Fos expression was assessed in female voles that were late in pregnancy, nonpregnant or at one of three different times postpartum (0-8, 12-24, and 24-48 h, respectively). A significant increase in the number of cells displaying Fos immunoreactivity (Fos-ir) was observed during the 0-8 h and 12-24 h postpartum time periods in the accessory olfactory bulbs, medial preoptic area, hypothalamus (specifically, the supraoptic nucleus, ventro-medial hypothalamus, and paraventricular nucleus), lateral septum, bed nucleus of the stria terminalis, and primary somatosensory area of the brain. The number of Fos-ir cells decreased after 24 h postpartum. There were no significant changes in Fos-ir cell numbers in the primary olfactory bulbs, hippocampus, or caudate putamen. The neural activation of the medial preoptic area, accessory olfactory bulbs, hypothalamus, and bed nucleus is consistent with reports in rats of Fos induction associated with the onset of maternal behavior. In voles postpartum estrous behavior begins and ends 0-12 h after parturition. Maternal behavior, including lactation, is initiated at the same time but persists for several weeks. The highest Fos-ir cell numbers reported here coincide with the timing of postpartum estrous behavior in this species.

Animals↗
PubMed1999

Castration does not inhibit aggressive behavior in adult male prairie voles (Microtus ochrogaster).

The relationship between castration and reduced male aggression is well established. However, anecdotal observations of male prairie voles (Microtus ochrogaster) suggest that castration does not reduce aggressive behavior. To investigate the role of testicular androgens on aggressive behavior, castrated or gonadally intact male prairie voles were paired in a neutral arena with a gonadally intact vole. Castration did not reduce the frequency of intermale aggression. In Experiment 2, aggressive behavior was examined further using resident-intruder, grouped aggression, and aggression against a lactating female models. Again, castration did not affect the frequency of aggression in male prairie voles. Taken together, the results of this study suggest that aggressive behavior may be independent of gonadal steroid hormones in adult male prairie voles.

Aggression↗
PubMed1999

Ejaculatory abnormalities in mice lacking the gene for endothelial nitric oxide synthase (eNOS-/-).

Nitric oxide (NO) has been established as a neurotransmitter in both the central and peripheral nervous systems. Three isoforms of its synthetic enzyme, NO synthase (NOS), have been identified: 1) in the endothelial lining of blood vessels (eNOS), 2) an inducible form found in macrophages (iNOS), and 3) in neurons (nNOS). Previous studies using pharmacological agents that block all three isoforms of NOS have revealed that NO mediates several aspects of reproductive physiology and behavior, including anomalies in male sexual behavior and erectile function. To determine the specific contribution of the endothelial isoform of NOS in male reproductive behavior, we studied mice missing the gene for only eNOS (eNOS-/-). Wild-type (WT) and eNOS-/- animals were placed with an estrous WT female and observed for 45 min. Both WT and eNOS-/- mice displayed equivalent motivation to mount the stimulus female. However, eNOS-/- mice exhibited striking anomalies in ejaculatory function. A higher percentage of eNOS-/- than WT mice ejaculated during the testing period (p < 0.001). This increased propensity to ejaculate was apparently due to reduced stimulation required to elicit ejaculation; eNOS-/- mice required significantly fewer mounts (p < 0.003) and intromissions (p < 0.001) to ejaculate compared to WT mice. Taken together, these results suggest that NO synthesized by eNOS may be involved in ejaculatory physiology, but not sexual motivation.

Animals↗
PubMed1999

Nocturnal motor coordination deficits in neuronal nitric oxide synthase knock-out mice.

Nitric oxide is formed in the brain primarily by neurons containing neuronal nitric oxide synthase (nNOS), though some neurons may express endothelial NOS (eNOS), and inducible NOS (iNOS) only occurs in neurons following toxic stimuli. Mice with targeted disruption of nNOS (nNOS-) display distended stomachs with hypertrophied pyloric sphincters reflecting loss of nNOS in myenteric plexus neurons. nNOS- animals resist brain damage following middle cerebral artery occlusions consistent with evidence that excess release of nitric oxide mediates neurotoxicity in ischemic stroke. Neuronal NOS- mice have no grossly evident defects in locomotor activity, breeding long-term depression in the cerebellum, long-term potentiation in the hippocampus, and overall sensorimotor function. However, nNOS- animals display excessive, inappropriate sexual behavior and dramatic increases in aggression. Because the cerebellum possesses the greatest levels of nNOS neurons in the brain, it was surprising that presumed cerebellar functions such as balance and coordination were grossly normal in nNOS- mice. These previous studies were all conducted during the day (between 1400 and 1600, lights on at 0700). We now report striking, discrete abnormalities in balance and motor coordination in nNOS-mice reflected selectively at night.

Animals↗
PubMed1999

Activation of the immune-endocrine system with lipopolysaccharide reduces affiliative behaviors in voles.

In Experiment 1, individually housed male meadow voles (Microtus pennsylvanicus) and prairie voles (Microtus ochrogaster) were injected with lipopolysaccharide (LPS) and exhibited the expected decrease in testosterone and increase in corticosterone and interleukin-1beta concentrations 3 hr later, indicating activation of the endocrine and immune systems. In Experiment 2, LPS- and saline-injected males were tethered in a 3-chamber partner preference apparatus. The time females spent in each chamber with a male, as well as the amount of time spent in social contact, was monitored. Female prairie voles, but not meadow voles, spent more time in the chamber with saline- than with LPS-injected males. LPS-injected male prairie and meadow voles engaged in less social contact with female conspecifics than did saline-injected males. These data suggest that LPS modifies physiology and behavior in male voles and that females may use these changes to discriminate healthy from potentially infected males.

Animals↗
PubMed1999

Cerebral near infrared spectroscopy: emitter-detector separation must be increased.

We have compared the effect of increasing optode separation (range 0.7-5.5 cm) on the sensitivity of near infrared spectroscopy (NIRS) to discrete reductions in scalp and cerebral oxygenation in 10 healthy men (mean age 32, range 26-39 yr) using multichannel NIRS. During cerebral oligaemia (a mean reduction in middle cerebral artery flow velocity of 47%) induced by a mean reduction in end-tidal PCO2 of 2.4 kPa, the decrease in oxyhaemoglobin detected by NIRS became significantly greater with increasing optode separation (P < 0.0001). In response to scalp hyperaemia induced by inflation and release of a pneumatic scalp tourniquet, increases in oxyhaemoglobin became significantly smaller with increasing optode separation (P < 0.0002). These results are consistent with theoretical models of the behaviour of NIR light in the adult head and support the concept of using multi-detector NIRS to separate intra- and extracranial NIR signal changes. However, the emitter-detector separation used by currently available cerebral oximeters is not large enough to provide optimal spatial resolution.

Adult↗
PubMed1999

Population structure and dynamics of Magnaporthe grisea in the Indian Himalayas.

The population genetics of Magnaporthe grisea, the rice blast pathogen, were analyzed in a center of rice diversity (the Uttar Pradesh hills of the Indian Himalayas) using multilocus and single-, or low-copy, DNA markers. Based on DNA fingerprinting with the multilocus probe MGR586 and single-locus probes, 157 haplotypes clustered into 56 lineages (at >/=70% MGR586 band similarity, each with unique single-locus profiles) and high diversity indices were detected among 458 isolates collected from 29 sites during 1992-1995. Most valleys sampled had distinct populations (73% of the lineages were site specific) with some containing one or a few lineages, confirming the importance of clonal propagation, and others were very diverse. Widely distributed lineages suggested that migration occurs across the region and into the Indo-Gangetic plains. Repeated sampling at one site, Matli, (170 isolates, 1992-1995) yielded 19 lineages and diversity significantly greater than that reported from similar samples from Colombia and the Philippines. Analysis of allelic associations using pairwise comparisons and multilocus variance analysis failed to reject the hypothesis of gametic phase equilibrium. The Matli population shifted from highly diverse in 1992 to almost complete dominance by one lineage in 1995. Such population dynamics are consistent with recombination followed by differential survival of clonal descendants of recombinant progeny. At another site, Ranichauri, population (n = 84) composition changed from 2 to 11 lineages over 2 yr and yielded additional evidence for equilibrium. Sexually fertile and hermaphrodite isolates of both mating types were recovered from rice in both Matli and Ranichauri. We demonstrate that Himalayan M. grisea populations are diverse and dynamic and conclude that the structure of some populations may be affected to some extent by sexual recombination.

Crosses, Genetic↗
PubMed1999

Prospective, randomized, controlled trial to determine the effect of early enhanced enteral nutrition on clinical outcome in mechanically ventilated patients suffering head injury.

OBJECTIVE: To determine the effect of early enhanced enteral nutrition (EN) on clinical outcome of head-injured patients. DESIGN: Prospective, randomized, controlled trial. SETTING: Tertiary neurosurgical and trauma center. PATIENTS: Eighty-two patients suffering head injury and requiring mechanical ventilation. INTERVENTIONS: Patients were randomized to receive standard EN (gradually increased from 15 mL/hr up to estimated energy and nitrogen requirements) or enhanced EN (started at a feeding rate that met estimated energy and nitrogen requirements) from day 1. Good neurologic outcome (Glasgow Outcome Scale score of 4 or 5) was determined at 3 and 6 months after injury, and the incidence of infective and total complications was determined during the hospital stay up to 6 months. MEASUREMENTS AND MAIN RESULTS: Disease severity assessed by best preintubation Glasgow Coma Scale score, pupillary responses, Injury Severity Score, Acute Physiology and Chronic Health Evaluation II score, computed tomographic scan categorization, and age was similar in both groups. Intervention patients had a higher percentage of energy (p = .0008) and nitrogen (p<.0001) requirements met by EN in the first week after injury. Neurologic outcome at 6 months was similar between groups, but there was a tendency for more intervention patients to have a good neurologic outcome at 3 months than control patients (61% vs. 39%, p = .08). Fewer intervention patients had an infective complication (61% vs. 85%, p = .02) or more than one total complication (37% vs. 61%, p = .046) compared with control patients. Enhanced EN was associated with a reduction in the ratio of serum concentration of C-reactive protein to albumin up to day 6 after injury (p = .004). CONCLUSIONS: Enhanced EN appears to accelerate neurologic recovery and reduces both the incidence of major complications and postinjury inflammatory responses.

Brain Injuries↗
PubMed1999

Role of steroid hormones in Trichinella spiralis infection among voles.

Males are generally more susceptible to parasite infection than females. This sex difference may reflect the suppressive effects of testosterone and enhancing effects of estradiol on immune function. This study characterized the role of circulating steroid hormones in sex differences after infection with the nematode Trichinella spiralis. Because testosterone suppresses immune function and because polygynous males have higher circulating testosterone concentrations than monogamous males, sex differences in parasite burden were hypothesized to be exaggerated among polygynous meadow voles compared with monogamous prairie voles. As predicted, sex differences in response to T. spiralis infection were increased among meadow voles; males had higher worm numbers than females. Male and female prairie voles had equivalent parasite burden. Overall, prairie voles had higher worm numbers than meadow voles. Contrary to our initial prediction, differences in circulating estradiol concentrations in females, testosterone concentrations in males, and corticosterone concentrations in both sexes were not related to the observed variation in T. spiralis infection. Taken together, these data suggest that not all sex differences in parasite infection are mediated by circulating steroid hormones and that adaptive-functional explanations may provide new insight into the causes of variation in parasite infection.

Animals↗
PubMed1999

Rhythmically firing neostriatal neurons in monkey: activity patterns during reaction-time hand movements.

While previous studies have identified rhythmically firing neurons (RFNs) in monkey neostriatum and these rhythmic firing patterns have been shown to evolve in neostriatal tonically active neurons (TANs) after dopamine input depletion, the activity patterns of RFNs during motor behavior are still far from completely understood. We examined the single-unit activity patterns of neostriatal neurons, recorded in awake behaving monkeys during a wrist movement task, for evidence of rhythmic activity. Monkeys made ballistic wrist flexion and extension movements in response to vibrotactile cues. Animals held a steady wrist position for 0.5 to 2.0 s while awaiting the onset of the go-cues (hold period). Although the majority of neostriatal neurons (274/306) did not fire rhythmically, approximately 10% of the neurons (32/306) fired rhythmically at 10-50 Hz during the hold period. Most RFNs (28/32) showed significant activity changes during the time between go-cue presentation and movement onset (premovement activity). One-half of RFNs exhibited premovement activity that differed as a function of movement direction. Only one RFN may have responded to the delivery of a fruit juice reward. Neuronal firing was analyzed using interspike interval distributions, autocorrelations, and serial correlation techniques. These analyses showed that the activity patterns of most RFNs were consistent with an integrate-and-fire model of neuronal rhythm generation. Changes in RFN activity patterns during the premovement interval and intertrial variations in firing frequency could be explained by changes in the general level of excitatory input. These observations are consistent with the firing properties reported for neostriatal cholinergic interneurons. It has been suggested that tonically active neurons may be cholinergic interneurons and that these neurons show changes in activity related to specific aspects of behavioral paradigms, such as rewards. RFNs may constitute a special class of TANs. The results presented here suggest that RFNs may have a role in movement initiation. We speculate that RFNs may modulate the propagation of cortical oscillations via basal ganglia-thalamic-cortical loops.

Animals↗
PubMed1999

Photoperiod affects the gonadotropin-releasing hormone neuronal system of male prairie voles (Microtus ochrogaster).

In order to maximize survival, animals inhabiting temperate and boreal latitudes exhibit numerous adaptations to changing seasons. Central among this suite of coping strategies is the cessation of breeding during the suboptimal conditions of winter. Many nontropical rodents inhibit reproduction well in advance of winter in response to short day lengths. Male prairie voles (Microtus ochrogaster) are small temperate-zone rodents that vary in their reproductive response to photoperiod. Some male voles undergo complete gonadal regression during short days (responders) while others fail to inhibit reproduction when exposed to short day lengths (nonresponders). The neuroendocrine mechanisms regulating this differential response to photoperiod have not been investigated in this species. Presumably, photoperiod can act at any or all levels of the hypothalamo-pituitary-gonadal (HPG) axis to regulate reproduction. The present study sought to determine the contribution of the GnRH system to this variable reproductive response to photoperiod. Male prairie voles were housed in either long or short day lengths for 10 weeks. As shown with immunohistochemistry, voles that underwent gonadal regression in response to short photoperiods exhibited increased GnRH neuron numbers in the preoptic area/anterior hypothalamus (POA/AH) relative to both long-day animals and short-day voles that maintained reproductive function. Mean optical density of staining and cell size did not differ among groups. These data suggest that the differential reproductive response to photoperiod in male voles is mediated, in part, by alterations in the GnRH neuronal system.

Adaptation, Physiological↗
PubMed1999

Circadian locomotor analysis of male mice lacking the gene for neuronal nitric oxide synthase (nNOS-/-)

Nitric oxide (NO) is an endogenous gas that functions as a neurotransmitter. Because NO is very labile with a half-life of less than 5 sec, most functional studies of NO have manipulated its synthetic enzyme, NO synthase (NOS). Three isoforms of NOS have been identified: (1) in the endothelial lining of blood vessels (eNOS), (2) an inducible form found in macrophages (iNOS), and (3) in neurons (nNOS). Most pharmacological studies to date have blocked all three isoforms of NOS. Previous studies using such agents have revealed that NO might be necessary for photic entrainment of circadian rhythms; general NOS inhibitors attenuate phase shifts of free-running behavior, light-induced c-fos expression in the suprachiasmatic nucleus (SCN), and phase shifts of neural firing activity in SCN maintained in vitro. To assess the specific role of nNOS in mediating entrainment of circadian rhythms, mice with targeted deletion of the gene encoding the neuronal isoform of NOS (nNOS-/-) were used. Wild-type (WT) and nNOS-/- mice initially were entrained to a 14:10 light:dark (LD) cycle. After 3 weeks, the LD cycle was either phase advanced or phase delayed. After an additional 3 weeks, animals were held in either constant dim light or constant dark. WT and nNOS-/- animals did not differ in their ability to entrain to the LD cycle, phase shift locomotor activity, or free run in constant conditions. Animals held in constant dark were killed after light exposure during either the subjective day or subjective night to assess c-fos induction in the SCN. Light exposure during the subjective night increased c-fos expression in the SCN of both WT and nNOS-/- mice relative to animals killed after light exposure during the subjective day. Taken together, these findings suggest that NO from neurons might not be necessary for photic entrainment.

Animals↗
PubMed1999

Short photoperiods evoke testicular apoptosis in white-footed mice (Peromyscus leucopus).

Many small, nontropical mammals stop breeding during winter. Chronic exposure of males to short days (<12.5 h light/day) causes the testes to atrophy and both steroidogenesis and gametogenesis to decrease. Male white-footed mice (Peromyscus leucopus) exposed to inhibitory short day lengths provide a natural animal model to study the cellular mechanisms regulating testicular regression. In the present study, the possible role of apoptosis was assessed during naturally occurring, short day-induced gonadal regression in white-footed mice by in situ terminal transferase-mediated end labeling (TUNEL), quantitative DNA 3'-end-labeling autoradiography (laddering) of DNA fragments, and quantification of Fas protein expression, an early initiator of apoptosis. Sexually mature male mice were exposed to short (8 h of light, 16 h of darkness) or long (16 h of light, 8 h of darkness) day lengths for 2, 4, 6, 8, or 10 weeks; gonads were then removed and processed for detection of apoptotic activity. In common with previous studies, the first significant reduction in relative testis mass was observed at week 10 of short day exposure. A 2- to 3-fold increase in apoptotic (TUNEL-positive) germ cells per seminiferous tubule was observed in the testes of mice exposed to short days for 4, 6, 8, or 10 weeks compared with the testes of long day animals. The extent of 3'-end labeling of low mol wt DNA increased with 4-8 weeks of short day exposure. Western blot analysis revealed an up-regulation of the Fas protein in the testes of short day males at 4, 8, and 10 weeks. Fas staining was primarily localized to spermatocytes and spermatids. Plasma testosterone concentrations decreased in short compared with long day animals after 6, 8, or 10 weeks. The increase in TUNEL positive-labeled germ cells, testicular DNA fragmentation, and up-regulation of the Fas protein before short day reductions of testis mass and function suggest that apoptosis is important for the mediation of photoperiod-induced testicular regression in white-footed mice.

Animals↗