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Biomedical subjects

J R Galler

Publications and source records attributed to J R Galler.

At least 19 recordsLinked to original sources
PubMed2005

Prenatal protein malnutrition induces a phase shift advance of the spontaneous locomotor rhythm and alters the rest/activity ratio in adult rats.

Evidence is accumulating for significant structural and functional changes within the central nervous system (CNS) following prenatal protein malnutrition. Included among the structures that are likely to be affected are the suprachiasmatic nuclei (SCN) involved in the regulation of locomotor activity, sleep-wake cycle, and drinking behavior. To determine the effects of prenatal protein malnutrition on the spontaneous activity rhythm, 24 h radiotelemetric measurements were recorded over an 8-day period. Male offspring of rats provided with protein-deficient (6% casein) or adequate (25% casein) diets for 5 weeks prior to mating and throughout pregnancy were studied. Well nourished rats displayed a rise in activity level during the first hour of the 12h light phase, whereas prenatally malnourished rats displayed this increase during the 12h dark phase, approximately 50 min before lights on, reflecting a significant phase advance in this group. In addition, cosinor analysis revealed that the alpha/rho relationship was affected in the previously malnourished group, the activity phase being shorter than in the well-nourished animals. These findings suggest changes in the regulatory systems controlling the locomotor activity rhythm as a consequence of prenatal protein malnutrition. Alterations in entrainment to the light-dark cycle, and/or in the coupling force of the circadian oscillators are all candidate mechanisms.

Animals↗
PubMed2002

Birthdates and number of neurons in the serotonergic raphe nuclei in the rat with prenatal protein malnutrition.

The effect of prenatal protein deprivation on timing of neurogenesis and on number of neurons generated in the serotonergic dorsal (DR) and median raphe (MR) nuclei of the rat was studied. These neurons are of interest because their neurogenesis occurs during the period of malnutrition and their axonal projections participate in the earliest stages of brain development. In this study, dams were maintained on a 25% casein diet or a 6% casein diet 5 weeks prior to mating and throughout pregnancy. At birth, all pups were cross-fostered to dams on a 25% casein diet. Bromodeoxyuridine, a thymidine analog that is incorporated into nuclear deoxyribonucleic acid during the cell cycle synthetic phase, was used as a marker of neurogenesis. Bromodeoxyuridine was administered on either embryonic day 11, 12, 13 or 14. On postnatal day 30, serial sections of raphe nuclei were processed with bromodeoxyuridine immunocytochemistry to determine the number of raphe cells generated on each day and with Nissl stain to determine the total number of cells generated. There were no significant differences between the two diet groups in timing of generation or in total number of cells generated, indicating that neurogenesis of these early generated neurons appears unaffected by concomitant protein deprivation.

Animals↗
PubMed2001

Development and modulation of GABA(A) receptor-mediated neurotransmission in the CA1 region of prenatally protein malnourished rats.

Prenatal protein malnutrition has been demonstrated to result in alterations in the serotonergic and GABAergic neurotransmitter systems in the rat hippocampus. In the present study, whole-cell patch clamp recordings of CA1 pyramidal cells were employed in an effort to gain insight into the specific cellular locus and functional consequences of the previously reported changes. Hippocampal slices were prepared from Sprague-Dawley rats whose dams were fed either a normal (25% casein) or low (6% casein) protein diet during pregnancy. The development of GABA(A) receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs) and their modulation by the benzodiazipine agonist zolpidem were compared in cells from the two nutritional groups at postnatal days 7, 14, 21 and >90. The modulation of mIPSCs by serotonin was also examined in cells from 21 day old rats. No significant differences were observed in the characteristics of mIPSCs in cells from control vs. prenatally protein malnourished rats at any of the ages studied, although there was a trend for a higher frequency of mIPSCs in adult (>p90) prenatally protein malnourished rats. At all ages, zolpidem produced a significant increase in the mean decay time of mIPSCs that was not significantly different in cells from the two nutritional groups. Serotonin application resulted in a significant increase in the frequency of mIPSCs in CA1 pyramidal cells but there was no significant difference between cells from the two nutritional groups in the characteristics of this effect. These data demonstrate that the previously observed alterations in the serotonergic and GABAergic systems that result from prenatal protein malnutrition do not have significant functional consequences at a single cell level in the CA1 region of the rat hippocampus as measured in vitro.

Aging↗
PubMed2000

Chlordiazepoxide-induced spatial learning deficits: dose-dependent differences following prenatal malnutrition.

The sensitivity of prenatally protein-malnourished rats to the amnestic properties of the benzodiazepine (BZ) receptor agonist, chlordiazepoxide (CDP), was studied in the male offspring of rats provided with a protein-deficient diet (6% casein) for 5 weeks prior to mating and throughout pregnancy. Rats were tested during acquisition of the submerged platform version of the Morris water maze task using three systemic doses of CDP (3.2, 5.6, and 7.5 mg/kg i.p.) at two ages (day 30 and day 90). At 30 days, prenatally malnourished rats showed less sensitivity to the amnestic effect of the 5.6-mg/kg dose when compared with well-nourished controls by displaying shorter swim paths during acquisition and a more selective search of the target quadrant upon removal of the platform (probe trial). At 90 days, prenatally malnourished rats again showed less sensitivity to CDP at a dose of 5.6 mg/kg, but more sensitivity to the 3.2-mg/kg dose (indicated on the probe trial). No obvious relationship was identified between the nutritional group differences in behavioral sensitivity to CDP at 90 days and their BZ receptor density in the hippocampus or medial septum. It can be concluded that prenatal malnutrition alters the amnestic response to CDP in a dose-dependent and developmentally specific manner, thus providing further support for functional changes within the GABAergic system subsequent to malnutrition.

Animals↗
PubMed2000

Prenatal protein malnutrition results in increased frequency of miniature inhibitory synaptic currents in rat CA1 pyramidal cells.

There is growing evidence for an effect of prenatal protein malnutrition on the GABAergic neurotransmitter system in the rat hippocampus and associated structures. In the present study, we examined the functional electrophysiological consequences of observed alterations in GABA(A) and benzodiazepine receptor systems. Whole-cell patch clamp recordings of spontaneous and of miniature inhibitory postsynaptic currents (mIPSCs) generated by CA1 pyramidal cells were performed in in vitro hippocampal slices prepared from control and prenatally protein malnourished adult male rats. The characteristics of spontaneous synaptic currents were unaltered by the prenatal insult, as were the amplitudes and kinetics of GABA(A) receptor-mediated mIPSCs. The frequency of mIPSCs, however, was significantly increased in CA1 pyramidal cells in slices prepared from prenatally malnourished vs. control rats. The effect of the benzodiazepine receptor agonist chlordiazepoxide on the characteristics of mIPSCs was also examined and found to be the same in cells from both nutritional groups. The increased frequency of mIPSCs together with the lack of a change in amplitude, kinetics, or modulation by benzodiazepines of mIPSCs in response to prenatal protein malnutrition indicate a presynaptic locus of effect of this insult.

2-Amino-5-phosphonovalerate↗
PubMed2000

Prenatal protein malnourished rats show changes in sleep/wake behavior as adults.

Prenatal protein malnutrition significantly elevates brain levels of serotonin in rats, and these levels remain elevated throughout their lives. This biogenic amine is involved in the regulation of many physiological functions, including the normal sleep/wake cycle. The present study examined the effects of prenatal protein malnutrition on the sleep/wake cycle of freely moving adult rats. Six prenatally protein malnourished (6% casein) and 10 well-nourished (25% casein) male rats (90-120-day-old) were chronically implanted with a standard set of electrodes (to record cortical electroencephalogram, neck muscle electromyogram, electrooculogram, and hippocampal theta wave) to objectively measure states of sleep and wakefulness. Six-hour polygraphic recordings were made between 10.00 and 16.00 h; a time when the rats normally sleep. Prenatally malnourished rats spent 20% more time in slow wave sleep (SWS) compared to the well-nourished rats. The total percentage of time spent in rapid eye movement (REM) sleep was 61% less in prenatally malnourished rats compared to well-nourished control rats. These findings demonstrate the adverse consequences of prenatal protein malnutrition on the quality and quantity of adult sleep in rats. These sleep changes are potentially detrimental to normal social behavior and cognitive functions. Prenatally malnourished rats are an excellent animal model to study the role of endogenous serotonin in the regulation of the normal sleep/wake cycle.

Aging↗
PubMed2000

Prenatally protein-malnourished rats are less sensitive to the amnestic effects of medial septal infusions of chlordiazepoxide.

Evidence is mounting that prenatal protein malnutrition affects the physiological properties of the GABAergic neurotransmitter system in rats. To investigate the functional behavioral consequences of these changes, chlordiazepoxide (CDP, a positive modulator of the GABA(A) receptor) was applied directly to the medial septum and the amnestic response appraised. In adulthood, male offspring of rats provided with a protein-deficient diet (6% casein) for 5 weeks prior to mating and throughout pregnancy underwent stereotaxic surgery to implant steel cannulae aimed at the medial septum. After recovery, spatial learning performance in the submerged platform version of the Morris water maze task was assessed immediately following a 1 microl infusion of either artificial cerebrospinal fluid (aCSF), or one of three doses of CDP (15, 30 and 60 nmol). Well-nourished control rats demonstrated a robust amnestic response to intraseptal CDP. During task acquisition, well-nourished rats administered each of the doses exhibited significantly longer escape latencies than those given aCSF. On the probe trial (platform removed) a lower proportion of time was spent in the target quadrant (all three doses) at a greater average distance from the former platform location (30 and 60 nmol doses). In contrast, prenatally malnourished rats exhibited a muted sensitivity to CDP, most notable at the 30 nmol dose. These findings provide further support for functional changes within the GABAergic system consequent to malnutrition.

Animals↗
PubMed2000

Maternal depressive symptoms affect infant cognitive development in Barbados.

This longitudinal study is part of a series examining the relationships between maternal mood, feeding practices, and infant growth and development during the first 6 months of life in 226 well-nourished mother-infant dyads in Barbados. In this report, we assessed maternal moods (General Adjustment and Morale Scale and Zung Depression and Anxiety Scales), feeding practices (scales describing breast-feeding and other practices associated with infant feeding in this setting), and infant cognitive development (Griffiths Mental Development Scales). Multivariate analyses, with and without controlling for background variables, established significant relationships between maternal moods and infant cognitive development. Infants of mothers with mild moderate depression had lower Griffiths scores than infants of mothers without depression. Maternal depressive symptoms and lack of trust at 7 weeks predicted lower infant social and performance scores at 3 months. Maternal moods at 6 months were associated with lower scores in motor development at the same age. Although no independent relationships emerged between feeding practices and infant cognitive development, the combination of diminished infant feeding intensity and maternal depression predicted delays in infant social development. These findings demonstrate the need to carefully monitor maternal moods during the postpartum period, in order to maximize the benefits of breast-feeding and related health programs to infant cognitive development.

Adult↗
PubMed1999

Modulation of paired-pulse responses in the dentate gyrus: effects of prenatal protein malnutrition.

Since our major hypothesis is that prenatal protein malnutrition significantly affects hippocampal neuroplasticity, this study examined the effects of prenatal protein malnutrition on the modulation of dentate granule cell excitability in freely moving rats at 15, 30 and 90 days of age across the vigilance states of quiet waking (QW), slow-wave sleep (SWS) and rapid eye movement (REM) sleep. Using paired-pulse stimulation, the paired-pulse index (PPI), a measure of the type and degree of modulation of dentate granule cell excitability elicited by stimulation of the medial perforant path, was obtained for each vigilance state at each stage of development. Four specific measures of granule cell excitability were computed, namely, PPI using both population spike amplitude (PSA) and EPSP slope measures, absolute values of PSA(1) and EPSP(1) slope. PPI values obtained at 15, 30 and 90 days of age, however, were altered during normal ontogenetic development, but not by vigilance state. At 15 days of age, the malnourished group exhibits greater early inhibition of the PPI using the PSA measure at IPIs between 20 and 30 ms regardless of vigilance state, while at 30 days of age, the malnourished group exhibits greater facilitation at IPIs between 50 and 70 ms during QW and SWS, but not during REM sleep. In the control adult (PND90) and juvenile (PND30) animal, PSA(1) values are significantly higher during SWS than in QW or REM sleep. However, for the younger malnourished animals (PND15 and PND30), PSA(1) values were found to be significantly greater during REM sleep rather than SWS. Therefore, as the animal matures, there appears to be a shift in vigilance state dependent synaptic transmission through the hippocampal trisynaptic circuit from REM sleep to SWS in both control and malnourished animals, with the change occurring later in malnourished animals when compared to control ones. Furthermore, our findings suggests that prenatal protein malnutrition significantly alters modulation of dentate granule cell excitability (i.e., PPI values using the PSA measure) during the earlier stages of development but not in adulthood.

Aging↗
PubMed1999

The effects of median raphé electrical stimulation on serotonin release in the dorsal hippocampal formation of prenatally protein malnourished rats.

Our previous work had shown an enhanced inhibition in the hippocampal formation of prenatally protein malnourished rats. We have also found a diminishment in 5-hydroxytryptamine (5-HT) fibers in the hippocampal formation of malnourished rats as well as increased levels of 5-HT in the brain. The purpose of the present study was to determine 5-HT release in the dorsal hippocampal formation following electrical stimulation of the median raphé nucleus (MRN) in unanesthetized prenatally malnourished rats. Stimulation of this nucleus at 20 Hz in malnourished rats resulted in a significantly diminished release of 5-HT compared to well-nourished rats. The latter group showed a lesser, though still significant, decrease in 5-HT release following raphé stimulation. Basal release of 5-HT prior to stimulation was significantly higher in malnourished rats as compared to well-nourished controls. This may be the result of a decreased density of 5-HT neurons leading to a diminished control of release. Stimulation of the MRN in behaving malnourished animals may markedly affect the recurrent negative feedback collaterals onto somatodendritic 5-HT(1A) and 5-HT(1D) autoreceptors thus enhancing the inhibitory effects of stimulation of the median raphé on 5-HT release. Studies are underway to examine the sensitivity of both the somatodendritic and terminal 5-HT autoreceptors in malnourished animals, in order to understand possible mechanisms for our findings.

Analysis of Variance↗
PubMed1999

Maternal moods predict breastfeeding in Barbados.

This study was designed to identify psychosocial variables affecting early infant feeding practices in Barbados. The sample included 93 healthy women and infants born at the Queen Elizabeth Hospital who were extensively evaluated 7 weeks, 3 months, and 6 months after birth. Maternal moods were assessed with the Zung Depression and Anxiety Scales and the General Adjustment and Morale Scale. Feeding practices were evaluated using a questionnaire developed for this population. The prevalence of mild depression in this population was 16% at 7 weeks and increased to 19% at 6 months, whereas there were very few cases of moderate-to-severe depression. Disadvantaged environmental conditions, including less information-seeking by the mother, lower family income, and poor maternal health, were closely associated with increased symptoms of depression and anxiety in all women. However, significant predictive relationships between mood and feeding practices remained even when the effects of the home environment were controlled. Specifically, depressive symptoms at 7 weeks postpartum predicted a reduced preference for breastfeeding at current and later infant ages. Conversely, feeding practices did not predict maternal moods at later ages. These findings have important implications for public policy dealing with programs promoting breastfeeding. Early interventions designed to treat mild postnatal depression should be instituted early in the postpartum period to improve the chances for successful breastfeeding.

Adult↗
PubMed1999

Prenatal protein restriction increases sensitization to cocaine-induced stereotypy.

The present study characterized the total amount of stereotyped behavior following acute and repeated administration of cocaine in male and female prenatally protein malnourished rats. Adult offspring of female Sprague-Dawley rats fed either a low (6% casein) or adequate (25% casein) protein diet 5 weeks prior to mating and throughout their pregnancy were studied. Once every 3 days (for a total of six injections), half the rats from each nutritional treatment group (repeated exposure) were injected with cocaine (30 mg/kg, i.p.) and their total amount of stereotypy (rearing, forepaw treading, compulsive sniffing and head bobbing) monitored. The remaining rats received five saline injections followed by a cocaine injection on the last injection day (acute exposure group) and their behavioral response was also measured. Despite being slightly less sensitive to cocaine following their first injection, by the sixth injection, prenatally protein malnourished animals in the repeated-exposure group exhibited significantly greater sensitization to the psychomotor stimulant effects of cocaine than well-nourished controls. In the acute exposure groups, however, prenatally malnourished males, but not females, exhibited significantly more stereotypy than well-nourished subjects following a single cocaine injection. These findings have implications for characterizing addiction potential in the previously malnourished rats, as well as providing additional information regarding factors which can influence sensitization.

Animal Nutritional Physiological Phenomena↗
PubMed1998

Electrophysiological properties of rat hippocampal principal cells are unaltered by prenatal protein malnutrition.

There is growing evidence that prenatal protein malnutrition alters the development of the hippocampal formation in rats (Morgane et al., 1993; Galler et al., 1996; Almeida et al., 1996, for reviews). Little is known, however, of the possible functional consequences of prenatal malnutrition on the physiology of principal cells in the hippocampus. We have addressed this issue by comparing the electrophysiological properties of hippocampal neurons (dentate granule cells and CA1 pyramidal cells) in slices prepared from control and from prenatally protein malnourished adult male and female Sprague-Dawley rats. We found no significant effect of the prenatal protein malnutrition insult upon a number of intrinsic membrane properties measured with whole-cell current clamp recordings, including: resting membrane potential, input resistance, and membrane time constant, or on action potential characteristics such as threshold, amplitude, and/or firing frequency. Additionally, we saw no effect of prenatal malnutrition upon extracellular measures of glutamatergic synaptic transmission such as the presynaptic fiber volley, excitatory postsynaptic potential or population spike amplitude at the perforant path to dentate granule cell synapse or at the Schaffer collateral to CA1 pyramidal cell synapse. In conclusion, we have demonstrated that prenatal protein malnutrition does not result in significant alterations of the cellular physiological properties of these two types of principal neurons in the adult rat hippocampus.

Aging↗
PubMed1998

Infant feeding practices in Barbados predict later growth.

This longitudinal study was designed to examine reciprocal relationships between feeding practices and infant growth over the first 6 mo of life. The following three hypotheses were tested: 1) early feeding practices predict later infant growth; 2) early infant growth predicts later feeding practices; and 3) these relationships occur after controlling for related background variables. The sample included 226 healthy, well-nourished infants born at the Queen Elizabeth Hospital, Bridgetown, Barbados. Assessments were made at birth, 7 wk, and 3 and 6 mo of age. Factor analysis of a feeding practices questionnaire for those mothers who attended all three postnatal visits yielded five uncorrelated factors. Three of these factors, preference for breast-feeding, feeding intensity and feeding difficulty, declined with infant age. Two of these factors, father helps and relatives help, increased with infant age. Several background variables, including maternal age, anthropometry and reproductive history, and reliance on outside sources of information were correlated with infant growth. Multivariate analyses confirmed all three hypotheses. The group of feeding practices (particularly the preference for breast-feeding) at 7 wk predicted increases in infant lengths at subsequent ages. Conversely, infant weights at 3 and 6 mo predicted subsequent feeding practices, especially feeding intensity. These reciprocal relationships remained even after statistically controlling for the influence of the background variables. Implications for public policy include the need for comprehensive programs advocating breast-feeding and supporting the general health of mothers and infants.

Aging↗
PubMed1998

Prenatal malnutrition-induced changes in blood pressure: dissociation of stress and nonstress responses using radiotelemetry.

A link between prenatal malnutrition and hypertension in human populations has recently been proposed. Rat models of prenatal malnutrition have provided major support for this theory on the basis of tail-cuff measurements. However, this technique requires restraint and elevated temperature, both potential sources of stress. To determine the effect of prenatal protein malnutrition on blood pressure under nonstress conditions, 24-hour radiotelemetric measurements were taken in the home cage. Male rats born to dams fed a 6% casein diet for 5 weeks before mating and throughout pregnancy were studied in early adulthood (from 96 days of age). During the waking phase of their cycle but not the sleep phase, prenatal malnutrition gave rise to small but significant elevations of diastolic blood pressure and heart rate compared with well-nourished controls. Direct effects of stress on blood pressure responses were determined in a second experiment using an olfactory stressor. Prenatally malnourished rats showed a greater increase in both systolic and diastolic pressures compared with well-nourished controls during the first exposure to ammonia. A different pattern of change of cardiovascular responses was also observed during subsequent presentations of the stressor. These findings of a small baseline increase in diastolic pressure consequent to prenatal malnutrition, but an augmented elevation of both systolic and diastolic pressures after first exposure to stress, suggest the need to reevaluate interpretation of the large elevations in blood pressure previously observed in malnourished animals using the stressful tail-cuff procedure.

Age Factors↗
PubMed1998

Prenatally malnourished female but not male rats show increased sensitivity to MK-801 in a differential reinforcement of low rates task.

A reduced behavioral sensitivity to drugs acting on central GABAergic, serotonergic, opioid and cholinergic systems has previously been identified in predominantly male malnourished animals. The present study sought to compare the effects of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 on responding maintained by a differential reinforcement of low rates (DRL-18s) operant schedule in two groups of rats with different prenatal nutritional histories (well-nourished and protein restricted). The schedule required that the rats space their responses at least 18 s apart in order to obtain food reinforcement (timing behavior). After training to a stable high proficiency, MK-801 was administered to female rats (Experiment 1) at doses of 0 (saline), 0.004, 0.008, 0.016, 0.024 or 0.032 mg/kg (doses expressed as the free-base). MK-801 produced dose-dependent decreases in the percentage efficiency of responding and the number of rewarded responses, with dose-dependent increases in the number of responses emitted. Prenatal malnutrition significantly shifted the inter-response time (IRT) curve to the left, relative to that of the well-nourished controls, leading to a significantly lower efficiency and a lower number of reinforcers, at an MK-801 dose of 0.016 mg/kg. In Experiment 2, the effect of MK-801 on DRL performance was compared between male and female rats after prenatal malnutrition. In general, females proved more sensitive to MK-801 than males. Consistent with Experiment 1, a significantly greater drug impairment was observed in prenatally malnourished females compared with well-nourished females, albeit at a slightly higher dose (0.032 mg/kg). Prenatal malnutrition did not alter the drug response in male rats. These findings suggest that the behavioral response to NMDA blockade is augmented in adult female, but not male, rats after prenatal malnutrition.

Animals↗
PubMed1997

Effects of diet on sensitization to cocaine-induced stereotypy in female rats.

The progressive increase in cocaine-induced stereotyped behavior that accompanies repeated cocaine injections (sensitization) was examined in rats consuming different diets. Adult female Sprague-Dawley rats were fed one of three diets: low protein (6% casein), adequate protein (25% casein), or a standard chow diet. Following 1 week of adaptation to the diets, the rats were injected every 3-4 days with either cocaine (30 mg/kg, IP) or saline, and the total amount of stereotypy was measured over a 90-min interval following each of four injections. Cocaine-induced stereotypy peaked at 40-50 min following each injection, after which it declined for all diet groups. With repeated injections, the total amount of stereotypy increased in all diet groups. By the fourth injection, the low protein diet group (6% casein) exhibited a slower onset and a possibly prolonged duration of cocaine-induced stereotypy when compared with the two adequate protein diet groups (25% casein and chow). Interestingly, the rats in the two purified diet groups (6% casein and 25% casein) exhibited significantly more stereotypy across injections than those in the chow diet group. Weight differences did not explain the differences in stereotypy present among the diet groups. This study concludes that diet significantly alters the pattern of cocaine-induced stereotypy in female rats, especially after repeated exposure.

Animal Nutritional Physiological Phenomena↗