PubMed Health⌕ Search

Biomedical subjects

Richard E Brown

Publications and source records attributed to Richard E Brown.

At least 19 recordsLinked to original sources
PubMed2006

Age-related changes in visual acuity, learning and memory in C57BL/6J and DBA/2J mice.

The DBA/2J mouse is a model of age-related pigmentary glaucoma in humans. Visual detection, pattern discrimination and visual acuity were evaluated in DBA/2J, C57BL/6J, B6.mpc1d (a C57 congenic strain) and D2.mpc1b (a D2 congenic strain) mice at 6, 12, 18 and 24 months of age. Mice were also tested in the Morris Water Maze and olfactory discrimination learning task. At 6 months, DBA/2J and D2.mpc1b mice outperformed C57BL/6J and B6.mpc1d mice in the visual detection task and there were no strain differences in performance on the water maze. At 12, 18 and 24 months, C57BL/6J and B6.mpc1d mice outperformed DBA/2J and D2.mpc1b mice in the vision tasks and in the water maze. Strains did not differ in the olfactory learning task. Therefore, loss of visual function occurs between 6 and 12 months of age in DBA/2J mice. Strain differences in visual task performance accounted for a significant proportion of the variance in measures of learning and memory in the water maze at 12, 18 and 24 months of age.

Aging↗
PubMed2006

The life and work of Donald Olding Hebb.

In his book, The Organization of Behavior, Donald Olding Hebb introduced the concepts of synaptic plasticity and cell assemblies to provide a theory of the neurophysiological basis of behaviour. Hebb's ideas, as presented in this book and other writings, influenced all areas of psychology and neuroscience. Hebb was born in Chester, Nova Scotia, Canada and attended Dalhousie University (BA, 1925) and McGill University (MA, 1932). His PhD from Harvard in 1936 was supervised by Karl Lashley. Hebb worked with the neurosurgeon Wilder Penfield at the Montreal Neurological Institute for two years, taught at Queen's University in Kingston, Ontario, and was a research assistant with Lashley at the Yerkes Primate Labs in Florida before he became a professor of Psychology at McGill University in 1947. At McGill he taught the first year psychology course and wrote an introductory textbook in Psychology. Throughout his career, Hebb made many research discoveries, trained a number of researchers and won many honours. When he retired from McGill, he moved back to Nova Scotia, and became a Professor Emeritus at Dalhousie University. This paper reviews Hebb's life and work and the impact of his ideas in psychology and neuroscience.

Canada↗
PubMed2005

Synergy of intramolecular hydrogen-bonding network in myo-inositol 2-monophosphate: theoretical investigations into the electronic structure, proton transfer, and pKa.

This work demonstrates the pivotal role that an intramolecular hydrogen-bonding network (intra-HBN) plays in the determination of the conformation of myo-inositol 2-monophosphate (Ins(2)P1), a member of the inositol phosphate family of compounds, which are important participants in the role that phosphates play in biological and environmental chemistry. For biologically significant compounds that contain phosphate and hydroxyl groups, Ins(2)P1 is a model system for studying both the primary forces that determine their conformations and their chemical properties from the effect of phosphate group addition. We performed ab initio calculations to determine the intra-HBN within important thermally accessible conformations for neutral Ins(2)P1 and its anions, Ins(2)P1(1-) and Ins(2)P1(2-). The results show that the global minima prefer 1a/5e structures where the phosphate group is in the axial position with all -OH groups in the equatorial positions. The calculations of transition state structures for ring inversion at each ionization state predict an activation energy of 18.16 kcal/mol for the neutral species in water, while the activation energy is lower for the charged compounds, 15.62 kcal/mol for Ins(2)P1(1-) and 12.48 kcal/mol for Ins(2)P1(2-). The pK(a) values of Ins(2)P1 were calculated by modeling the solvent as a polarizable continuum medium (PCM) and as explicit solvent molecules. These values are in good agreement with experimental data. A novel four-center pattern of hydrogen bonding was found to stabilize the system. The intramolecular proton transfer across a low barrier hydrogen bond between the charged phosphate and hydroxyl groups was found to occur under standard conditions with an activation energy that is less than 0.5 kcal/mol.

Electrons↗
PubMed2005

Maturation but not survival of dopaminergic nigrostriatal neurons is affected in developing and aging BDNF-deficient mice.

Brain-derived neurotrophic factor (BDNF) promotes survival of injured dopaminergic nigrostriatal neurons of the adult rodent substantia nigra pars compacta, as well their development in vitro. BDNF deficiency may play a role in Parkinson's disease, as the surviving dopaminergic nigrostriatal neurons have reduced levels of BDNF, and a BDNF gene polymorphism is present in a subpopulation of patients. Here, we investigated whether a lack of BDNF in early postnatal BDNF-/- mice or a chronic 50% reduction in BDNF levels in aging BDNF+/- mice would affect the survival of the dopaminergic nigrostriatal neurons. In general terms, BDNF-/- and BDNF+/- mice had morphologically and quantitatively normal nigrostriatal neurons at any time between postnatal day 14 (P14) and 18 months, when compared to their wild-type littermates. BDNF-/- mice (P14 and P21 only) had fewer dopaminergic dendrites in the substantia nigra, suggesting that BDNF plays a role in phenotypic maturation, but not in neuronal birth or survival. BDNF-/- mice also had aberrant tyrosine hydroxylase (TH) positive cell bodies in the pars reticulata. During adulthood and aging, BDNF+/- mice performed equally well as their wild-type littermates in tests of motor coordination, and both showed aging-related decreases in the size of the dopaminergic neurons as well as in motor coordination. These results suggest that chronic deficits in BDNF alone do not affect survival or function of dopaminergic nigrostriatal neurons during aging or potentially even in Parkinson's disease.

Aging↗
PubMed2005

Correction of pincer-nail deformities with autograft or homograft dermis: modified surgical technique.

The pincer-nail deformity is characterized by an excessively curved and distorted nail across the transverse dimension. Forty-nine sides (paronychial folds) were dissected off the distal phalanx periosteum with scissors and/or a small elevator. The dermis was placed between the paronychial fold and the plalanx to flatten the germinal and sterile matrix. Direct comparison of autograft dermis to homograft dermis did not show any significant differences in postcorrection appearance of the nail or relief of symptoms. Surgical time averaged 22 minutes less in those patients having reconstruction on both sides of one nail with homograft dermis.

Humans↗
PubMed2005

Dynamic versus static splinting of simple zone V and zone VI extensor tendon repairs: a prospective, randomized, controlled study.

The authors present the first prospective, randomized, controlled study comparing postoperative dynamic versus static splinting outcomes of patients following extensor tendon repair. Patients who incurred simple and complete lacerations of their extensor tendons in zones V and VI were enrolled into the study and underwent either static splinting (n = 17) or dynamic splinting (n = 17) following primary acute repair of tendons. Total active motion was improved in the dynamic group when compared with the static group in the injured digits at 4 weeks (180.5 +/- 4 degrees versus 131.3 +/- 61 degrees; p = 0.006), at 6 weeks (239 +/- 21.9 degrees versus 205.5 +/- 53.4 degrees; p = 0.048), and at 8 weeks (247+/- 19.8 degrees versus 216.3 +/- 36 degrees; p = 0.051), but not at 6 months (253.1 +/-18.8 degrees versus 250.5 +/- 32 degrees; p = 0.562). Similarly, total active motion averaged for all digits (injured and noninjured) of the involved hand was improved in the dynamic group over the static group at 4 weeks (209.8 +/- 31.3 degrees versus 140 +/- 58.2 degrees; p < 0.001) and at 6 weeks (241.5 +/- 17.2 degrees versus 217.1 +/- 42.4 degrees; p = 0.024), but not at 8 weeks (249.6 +/- 16 degrees versus 234.8 +/- 24.5 degrees; p = 0.215) or 6 months (252.3 +/- 14 degrees versus 249.1 +/- 31 degrees; p = 0.450). Grip strength outcomes demonstrated improved grip force for the dynamic group when compared with the static group at 8 weeks (81.3 +/- 18.0 percent versus 59.2 +/- 20.4 percent; p = 0.004) but not at 6 months (89.6 +/- 5.6 percent versus 82.1 +/- 22.0 percent; p = 0.595). Patients demonstrated forceful grip greater than or equal to 80 percent of the noninjured hand in 55 percent of patients in the dynamic group versus 15 percent of patients in the static group at 8 weeks. Patients demonstrated forceful grip greater than or equal to 80 percent of the noninjured hand in 100 percent of patients in the dynamic group versus 73 percent of patients in the static group at 6 months. The authors' findings suggest that dynamic splinting of simple, complete lacerations of the extensor tendons in zones V and VI provides improved functional outcomes at 4, 6, and 8 weeks but not by 6 months when compared with static splinting. Therefore, they recommend dynamic splinting of simple, complete extensor tendon lacerations in zones V and VI only to select patients who are motivated and desire earlier return to full functional capacity.

Adult↗
PubMed2004

Lubrication regimes in mesothelial sliding.

To function normally, the lungs, heart, and other organs must undergo changes in shape and size, sliding against surrounding body walls. It is not known whether the delicate mesothelial surfaces covering these organs and body wall are in contact during sliding, or if hydrodynamic pressure in the lubricating liquid increases separation between their surfaces. To address this question, we measured the coefficient of friction (mu) of the mesothelial surface of nine rat-abdominal walls sliding in saline on a smooth glass surface. Sliding at physiological velocities of 0.0123-6.14 cm/s with normal stresses of 50-200 Pa, mu varied with velocity (P<0.001). On average, mu was relatively high at low speeds (0.078 at 0.041 cm/s), decreased to a minimum at intermediate speeds (0.034 at 1.23 cm/s), and increased slightly again at higher speeds (0.045 at 6.14 cm/s), consistent with a mixed lubrication regime in which there is at least partial hydrodynamic separation of surfaces. We conclude that mesothelial surfaces, sliding under physiological conditions, are protected from excessive shear by hydrodynamic pressures that increase separation of surfaces.

Abdominal Wall↗
PubMed2004

Airflow synchronous with oscillatory acceleration reflects involuntary respiratory muscle activity.

To explore mechanisms causing involuntary airflow synchronous with oscillatory axial whole body acceleration (oscillatory axial acceleration, OAA) such as that during locomotion, we monitored airflow, acceleration, and electromyograms (EMGs) of the rib cage and abdominal muscles in standing subjects undergoing OAA at 3, 6, and 9 Hz at accelerations of 0.1-0.95 g. Subjects relaxed or performed static respiratory maneuvers at constant lung volume with glottis open. Oscillatory airflows (0.01-3.01 s(-1)) synchronous with OAA were not consistent with expectations for a passive respiratory system, and were larger during active respiratory efforts than during relaxation. Peak inspiratory airflow usually preceded peak upward acceleration by 90-180 degrees. In 80% of runs with respiratory muscles voluntarily activated or relaxed, EMGs showed activity synchronous with OAA. Changes in periodic muscle activity coincided with changes in oscillatory airflow. We conclude that periodic muscle activity, probably a reflex response to body wall deformation during OAA, strongly influences the involuntary airflow synchronous with OAA.

Acceleration↗
PubMed2004

Long-term methylphenidate treatment down-regulates c-fos in the striatum of male CD-1 mice.

Methylphenidate (Ritalin) is routinely prescribed to children with attention deficit hyperactivity disorder, but little is known about its long-term consequences on brain development. We treated pre- and peri-pubertal male CD-1 mice with repeated injections of methylphenidate hydrochloride (MPH) and quantified the expression of the immediate early gene c-fos in the striatum. A single injection of MPH (5 or 40 mg/kg) significantly elevated FOS immunoreactivity in the striatum in a dose-dependent manner, compared with saline. Repeated MPH treatment attenuated the effect of a single challenge dose of MPH on striatal c-fos expression. These results replicate those observed with rats and indicate that long-term use of MPH may alter neural activity by down-regulation of gene expression in the striatum.

Animals↗
PubMed2004

Sex differences in ultrasonic vocalizations and coordinated movement in the California mouse (Peromyscus californicus).

Geyer [Am. Zool. 21 (1981) 117] hypothesized that infant rodents increased the number of ultrasonic vocalizations when they moved in and out of the nest in order to elicit extended care from parents. We tested these hypotheses by recording ultrasonic vocalizations (USVs) and coordinated movements (locomotion and grooming) in California mouse and by recording USVs from pups before and after their parents retrieved them. In Experiment 1, USVs and coordinated movements were recorded from 2 to 30 days of age, in female and male Peromyscus californicus pups. USVs at 37, 42, 47, and 52kHz were digitized and recorded by computer and an event recorder program which was simultaneously used to record coordinated movement. Vocalizations persisted to 30 days of age. Vocalizations increased for both males and females after they spent more than 180s in coordinated movement and females vocalized more than males. Females also displayed more coordinated movement and earlier development of coordinated movement than males. There was no effect of litter size on USVs. In Experiment 2, the number of USVs emitted by pups and the latency of dams and sires to contact their pups and retrieve them was measured. There was no significant correlation between the number of USVs emitted by pups and the latency for a parent to contact or retrieve a pup. Results from Experiment 1 provided some support for Geyer's (1981) hypothesis and results from Experiment 2 did not support the hypothesis that the main function of USVs in California mouse pups was to elicit parental care.

Acoustic Stimulation↗
PubMed2004

Prenatal exposure to methylphenidate hydrochloride decreases anxiety and increases exploration in mice.

The administration of methylphenidate (MPH) to girls and adults has increased in the last decade. Given the similarity of MPH to cocaine and the increasing possibility of embryonic exposure, the gestational effects of this stimulant on development must be considered. We administered MPH (5 mg/kg) or saline to female CD-1 mice at three different periods during pregnancy [embryonic (E) days 8-10, 12-14, and 16-18]. MPH-exposed pups were compared with the saline-treated pups for changes in physical, motor, and behavioral development at postnatal day (PND) 3-11. In adulthood (>60 days of age) these mice were tested in the open field, elevated plus maze, and water maze, and given an acute MPH challenge. We observed limited effects of MPH exposure on early developmental variables. In adulthood, mice exposed to MPH on E8-10 exhibited a general decrease in anxiety-related behaviors and a concomitant increase in exploratory behavior. Prenatal MPH exposure did not alter water maze performance or the response to an acute MPH challenge. Our data provide an initial overview of the possible effects occurring as a result of prenatal exposure to MPH, and strongly suggest that further studies of the in utero and developmental effects of psychostimulants are needed.

Animals↗
PubMed2004

Effect of neonatal handling and paternal care on offspring cognitive development in the monogamous California mouse (Peromyscus californicus).

In the laboratory rat and mouse, neonatal handling enhances hippocampal-dependent learning in adulthood, an effect mediated by changes in maternal behavior toward the handled young. In the present study, we examined the interaction between neonatal handling and biparental care during the early postnatal period and its effect on cognitive function in adult California mice (Peromyscus californicus). We characterized the parental behavior of handled and nonhandled father-present and father-absent families over the first 15 days of life. We then assessed cognitive performance of male and female offspring in the Barnes maze and object recognition test after they were 60 days of age. We found that the amount of licking and grooming received by pups was decreased in father-absent families. By postnatal days 12-15, licking and grooming in handled, father-absent families were equivalent to that of nonhandled, father-present families. Handling enhanced novel object recognition in father-present male mice with no effect in females. In the nonhandled group, the presence of the father had no effect on object recognition learning in male or female mice. Handling also enhanced spatial learning in the Barnes maze. In nonhandled families, the presence of the father appeared to have no effect on spatial learning in the male offspring. Interestingly, spatial learning in nonhandled, father-absent, female offspring was similar to that of handled animals. The average amount of licking and grooming received by pups was negatively correlated with the average number of errors made on the first day of reversal training in the Barnes maze. These data support previous findings that neonatal handling facilitates learning and memory in adulthood, suggest that under certain environmental conditions, there is a sex difference in the response of pups to paternal care, and further demonstrate the importance of active parental investment for offspring cognitive development.

Animals↗
PubMed2003

A redox-mediated molecular brake: dynamic NMR study of 2-[2-(methylthio)phenyl]isoindolin-1-one and S-oxidized counterparts.

A redox-mediated molecular brake based on the sulfide-sulfoxide redox cycle is illustrated by modulation of the rotation rate of an N-Ar "shaft" by varying the oxidation state of sulfur in 2-[2-(sulfur-substituted)phenyl]isoindolin-1-ones. N-Ar rotational barriers in methylsulfinyl (2) and methylsulfonyl (3) derivatives (13.6 kcal mol(-1)) are approximately 5 kcal mol(-1) higher than sulfide 1. Rate reduction for N-Ar rotation is approximately 10(4) s(-1) (280 K) upon oxidation. Correlated N-pyramidalization/N-Ar rotation reduces the effectiveness of the brake by decreasing the energy barrier to N-Ar bond rotation.

Journal Article↗
PubMed2003

MHC-congenic mice (C57BL/6J and B6-H-2K) show differences in speed but not accuracy in learning the Hebb-Williams Maze.

We compared spatial learning and memory in male and female mice of two MHC-congenic strains (C57BL/6J and B6-H-2K) in two versions of the Hebb-Williams Maze. In the food-reward paradigm, males required fewer sessions to learn than females, but there were no strain differences in acquisition. There were no strain or sex differences in the number of errors during the test phase, but the B6-H-2K mice reached the goal box faster than the C57BL/6J mice. In the water-escape paradigm, the C57BL/6J mice required more sessions than the B6-H-2K mice during acquisition. There were no strain or sex differences in the number of errors or in the latency to swim to the goal box in the test phase of the water-escape task. There were no significant correlations between the number of sessions to learn the two mazes; the number of errors made or the latencies to reach the goal box in each maze. These results indicate that these two strains show differences in performance in the Hebb-Williams Maze, but do not differ in cognitive ability.

Analysis of Variance↗
PubMed2003

Elastohydrodynamic separation of pleural surfaces during breathing.

To examine effects of lung motion on the separation of pleural surfaces during breathing, we modeled the pleural space in two dimensions as a thin layer of fluid separating a stationary elastic solid and a sliding flat solid surface. The undeformed elastic solid contained a series of bumps, to represent tissue surface features, introducing unevenness in fluid layer thickness. We computed the extent of deformation of the solid as a function of sliding velocity, solid elastic modulus, and bump geometry (wavelength and amplitude). For physiological values of the parameters, significant deformation occurs (i.e. bumps are 'flattened') promoting less variation in fluid thickness and decreased fluid shear stress. In addition, deformation is persistent; bumps of sufficient wavelength, once deformed, require a recovery time longer than a typical breath-to-breath interval to return near their undeformed configuration. These results suggest that in the pleural space during normal breathing, separation of pleural surfaces is promoted by the reciprocating sliding of lung and chest wall.

Body Fluids↗
PubMed2003

Daily methylphenidate administration attenuates c-fos expression in the striatum of prepubertal rats.

Methylphenidate (Ritalin) is a psychostimulant drug used to treat children with attention deficit hyperactivity disorder. Despite its widespread and increasing clinical use, little is known about the long-term consequences of drug treatment. We compared the effects of a single injection of methylphenidate with that of long-term methylphenidate injections (one/day; 14 days) on immediate-early gene expression (c-fos) in the striatum of prepubertal male rats. Rats (25 days old) were injected once daily for 14 days with either saline or methylphenidate (1, 2 or 10 mg/kg), or for 13 days with saline followed by one injection of methylphenidate (1, 2 or 10 mg/kg) on day 14, and were sacrificed 2 h post-injection. Methylphenidate dose-dependently increased FOS immunoreactivity in the striatum. A single injection of methylphenidate (2 or 10 mg/kg) on day 14, following saline treatment for 13 days, caused a dramatic elevation in c-fos expression. This effect was significantly attenuated in animals treated chronically with methylphenidate (2 or 10 mg/kg) for the entire 14 days. Our data suggest that repeated methylphenidate treatment, at a clinically relevant dose (2 mg/kg), markedly inhibits immediate-early gene expression in the brain. This is the first demonstration of methylphenidate-induced modification of gene expression in developing rat striatum and may have implications for chronic methylphenidate use in children.

Animals↗
PubMed2003

Effects of the presence of the father on pup development in California mice (Peromyscus californicus).

Pup development and behavior in California mice were studied in litters housed with single mothers, or with fathers and mothers living together. Behavior of pups was recorded during a 15-min session every 2 days from 10 to 30 days of age. Physical contact, locomotion, grooming, and physical development indicators were recorded. It was found that the physical contact between siblings was greater and there was a tendency to have more contact between pup and either parent in the group in which the father was present. Finally, it was noted that the presence of the father did not affect either the first appearance of pup behavior during development or physical growth. In conclusion, the results indicate that the presence of the father had a greater influence on social contact between the different members of the litter than on pup behavioral development and physical growth.

Animals↗