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Biomedical subjects

V Luine

Publications and source records attributed to V Luine.

At least 19 recordsLinked to original sources

Dietary phytoestrogens enhance spatial memory and spine density in the hippocampus and prefrontal cortex of ovariectomized rats.

Long-term maintenance of ovariectomized rats (9 weeks) on chow containing high phytoestrogen levels (Purina LabDiet 5001) as compared to chow with minimal phytoestrogens (Harlan 2016 Teklad) was associated with better performance of the spatial memory task, object placement, increased dendritic spine density in CA1 and prefrontal cortex pyramidal neurons, and higher uterine weights. Object recognition memory, anxiety on an elevated plus maze and body weight were unaffected by phytoestrogen levels in the diet.

Administration, Oral↗

Ovariectomized rats show decreased recognition memory and spine density in the hippocampus and prefrontal cortex.

Effects of ovariectomy (OVX) on performance of the memory tasks, Object Recognition (OR) and Object Placement (OP), and on dendritic spine density in pyramidal neurons in layer II/III of the prefrontal cortex and the CA1 and CA3 regions of the hippocampus were determined. OVX was associated with a significant decline in performance of the memory tasks as compared to intact rats beginning at 1 week post OVX for OR and 4 weeks post OVX for OP. Golgi impregnation at 7 weeks post OVX showed significantly lower spine densities (17-53%) in the pyramidal neurons of the medial prefrontal cortex and the CA1, but not the CA3, region of the hippocampus in OVX compared to intact rats. These results suggest that cognitive impairments observed in OVX rats may be associated with morphological changes in brain areas mediating memory.

Animals↗

The gene encoding proline dehydrogenase modulates sensorimotor gating in mice.

Hemizygous cryptic deletions of the q11 band of human chromosome 22 have been associated with a number of psychiatric and behavioural phenotypes, including schizophrenia. Here we report the isolation and characterization of PRODH, a human homologue of Drosophila melanogaster sluggish-A (slgA), which encodes proline dehydrogenase responsible for the behavioural phenotype of the slgA mutant. PRODH is localized at chromosome 22q11 in a region deleted in some psychiatric patients. We also isolated the mouse homologue of slgA (Prodh), identified a mutation in this gene in the Pro/Re hyperprolinaemic mouse strain and found that these mice have a deficit in sensorimotor gating accompanied by regional neurochemical alterations in the brain. Sensorimotor gating is a neural filtering process that allows attention to be focused on a given stimulus, and is affected in patients with neuropsychiatric disorders. Furthermore, several lines of evidence suggest that proline may serve as a modulator of synaptic transmission in the mammalian brain. Our observations, in conjunction with the chromosomal location of PRODH, suggest a potential involvement of this gene in the 22q11-associated psychiatric and behavioural phenotypes.

Acoustic Stimulation↗

Catechol-O-methyltransferase-deficient mice exhibit sexually dimorphic changes in catecholamine levels and behavior.

Catechol-O-methyltransferase (COMT) is one of the major mammalian enzymes involved in the metabolic degradation of catecholamines and is considered a candidate for several psychiatric disorders and symptoms, including the psychopathology associated with the 22q11 microdeletion syndrome. By means of homologous recombination in embryonic stem cells, a strain of mice in which the gene encoding the COMT enzyme has been disrupted was produced. The basal concentrations of brain catecholamines were measured in the striatum, frontal cortex, and hypothalamus of adult male and female mutants. Locomotor activity, anxiety-like behaviors, sensorimotor gating, and aggressive behavior also were analyzed. Mutant mice demonstrated sexually dimorphic and region-specific changes of dopamine levels, notably in the frontal cortex. In addition, homozygous COMT-deficient female (but not male) mice displayed impairment in emotional reactivity in the dark/light exploratory model of anxiety. Furthermore, heterozygous COMT-deficient male mice exhibited increased aggressive behavior. Our results provide conclusive evidence for an important sex- and region-specific contribution of COMT in the maintenance of steady-state levels of catecholamines in the brain and suggest a role for COMT in some aspects of emotional and social behavior in mice.

Amino Acid Sequence↗

Restraint stress reversibly enhances spatial memory performance.

The effects of restraint stress on performance of a spatial memory task, the eight arm radial maze, was examined in rats. When stress was given for 6 h/day for 7 days and performance evaluated days 10-13 post stress, no effect on performance was noted; however, daily restraint stress for 13 days caused a small, but significant, enhancement of performance days 10-13 post stress. Stressed rats performed better than controls: their number of correct choices in the first 8 visits was higher than the controls, and stressed rats took fewer total choices to finish the maze than controls. Stress-dependent, enhanced performance does not appear permanent since further maze testing on days 14 and 15 post stress showed no differences between the groups. Performance of the stressed rats significantly correlated with their stress-induced, serum corticosterone levels measured after 6 h of restraint on the last day of restraint, day 13 (r = -0.63, P < 0.05); rats with higher levels of CORT took fewer choices to finish the task. Examination of hippocampal CA3c pyramidal neurons with Golgi techniques showed no effect of stress on the basal or apical dendritic arbors. Since our previous study showed that 21 days of restraint stress is associated with impaired spatial memory performance (10), these results suggest that the duration of stress may differentially affect learning/memory with shorter periods of stress serving an adaptive function while longer durations causing maladaptive changes.

Animals↗

Repeated stress causes reversible impairments of spatial memory performance.

Restraint stress, 6 h/day for 21 days, caused an impairment, during acquisition, of the performance of a spatial memory task, the eight-arm radial maze. The impairment was reversible, temporally limited and blocked by phenytoin, a blocker of excitatory amino acid action, or tianeptine, an antidepressant, which lowers extracellular serotonin. These effects on behavior parallel the reversible stress-induced atrophy of dendrites of hippocampal CA3 neurons that are also blocked by the drugs.

Animals↗

Effects of estradiol on radial arm maze performance of young and aged rats.

Gonadectomized male and female Sprague-Dawley rats, given estradiol (E2) via sc Silastic capsules that generated proestrus levels of hormones, were tested for spatial memory performance on an 8-arm radial maze. Performance of males, with or without E2, exceeded that of females, with or without E2, for choice accuracy parameters over 20 trials. In addition, males reached criterion earlier than females (6 vs 11 trials). There were no significant effects of E2 on performance of either sex. When a 1-h delay was instituted between the 4th and 5th choices, the performance of males remained better than that of the females, and E2 administration was associated with a small, but significant, improvement in performance of the males but not the females. E2 administration to 25-month-old males also did not affect performance in regular trials, but performance was enhanced in trials with delays of 1-3 h after the 4th choice. These results show that estradiol can influence spatial memory performance and suggest that E2 may be beneficial for age and/or disease-related memory impairments.

Aging↗

5,7-DHT facilitated lordosis: effects of 5-HT agonists.

The role of 5-HT (serotonin) in regulating lordosis was investigated by combining peripheral administration of the 5-HT agonists 8-OH-DPAT (8-hydroxy-2-[di-N-propylamino]tetralin) or TFMPP (1-[m-trifluoromethylphenyl]piperazine), with intrahypothalamic application of the 5-HT neurotoxin 5,7-DHT (5,7-dihydroxytryptamine). The 5-HT1A agonist, 8-OH-DPAT, significantly inhibited lordosis in 5,7-DHT-treated and non-treated rats. TFMPP, an agonist at 5-HT1B and 5-HT1C receptors, significantly facilitated lordosis in 5,7-DHT-treated and non-treated rats. Our results show that both inhibitory and facilitatory influences of hypothalamic 5-HT on lordosis, are modulated via postsynaptic receptors.

5,7-Dihydroxytryptamine↗

GABAergic-serotonergic interactions in regulating lordosis.

The GABAB agonist, baclofen, causes a dose-dependent decrease in lordosis, and this effect is attenuated following hypothalamic serotonin, (5-HT) lesions. Baclofen administration is associated with decreased 5-HT activity in the medial preoptic (mPOA) and ventromedial nuclei and enhanced 5-HT activity in the midbrain central gray, and with enhanced norepinephrine activity in the mPOA. Interactions between gamma-aminobutyric acid (GABA) and 5-HT may, therefore, be important for the activation of lordosis.

5,7-Dihydroxytryptamine↗

Spatial memory deficits in aged rats: contributions of monoaminergic systems.

Age-dependent changes in monoaminergic systems and their relationship to senescent memory decline were investigated in 4- and 25-26-month-old, female, Fischer 344 rats. Spatial memory performance was tested on an 8-arm radial maze, and levels of norepinephrine (NE), dopamine (DA) and metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid, serotonin (5-HT) and metabolite 5-hydroxyindoleacetic acid were measured in brain areas which contribute to memory function--basal forebrain cholinergic nuclei, subfields of the hippocampus, frontal and entorhinal cortex--and in monoaminergic cell body areas. The performance of aged subjects was significantly impaired as compared to young subjects, and alterations of 20-60% in monoamine and metabolite levels were measured in specific brain areas of aged rats. Decreased NE levels were found in basal forebrain nuclei and cortical areas but not in hippocampal subfields of aged rats. Changes in the 5-HT system were present in hippocampal, cortical and basal forebrain sites. Changes in the DA system were the most pervasive with aged rats showing decreased DA and/or metabolites in several basal forebrain nuclei, cortical areas, and the hippocampus. Aged rats showed 50% decreases of monoamines in locus coeruleus and substantia nigra and 30% decreases in the dorsal raphe nucleus. Some but not all of the changes correlated with memory performance. The present results in rats support evidence that age-dependent changes in monoaminergic function in discrete brain sites contribute to senescent memory decline and suggest that monoaminergic-cholinergic interactions within basal forebrain nuclei may be important in this decline.

Aging↗

Antivascular antibodies in the sera of patients with senile dementia of the Alzheimer's type.

We have investigated the specificities of antibrain antibodies in the sera of patients with senile dementia of the Alzheimer's type (SDAT). Using indirect immunofluorescence, we observed a vascular pattern of staining in 6 of 16 sera from patients with typical SDAT. None of 14 sera from age matched controls demonstrated this pattern of staining. The vascular pattern of staining seen with SDAT sera was identical to the immunofluorescent staining of brain by a monoclonal antibody to vascular basement membrane heparan sulfate proteoglycan. Immunoabsorption of SDAT sera with purified vascular proteoglycan abolished the staining of brain vessels. Using an enzyme linked immunoassay, 3 of the 6 vascular-reactive SDAT sera, and none of the 24 sera from aged controls, were shown to contain antibodies to purified vascular heparan sulfate proteoglycan. Proteoglycans play an important role in the barrier function of the blood-brain barrier. Autoimmune injury to the blood-brain barrier by antivascular antibody may play a role in the pathogenesis of dementia by permitting the passage of injurious substances into the brain.

Aged↗

Analysis of temporal and dose-dependent effects of estrogen on monoamines in brain nuclei.

Levels of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) were measured in hypothalamic and limbic nuclei of ovariectomized rats after various doses of estradiol and at various intervals after estradiol administration. Of 13 areas examined, time- and dose-dependent effects of estrogen on monoamine content were restricted to only a few, discrete areas which concentrate estradiol. Subcutaneous administration of 1-50 micrograms of estradiol benzoate (EB) and measurement of monoamines 24 h later was associated with dose-dependent increases of NE in the medial preoptic nucleus, diagonal band nucleus and periventricular area of the anterior hypothalamus, and increased levels of DA in the periventricular area of the preoptic area. No changes were found in 5-HT levels, but dose-dependent increases in the level of the 5-HT metabolite, 5-hydroxyindole acetic acid (5-HIAA), were measured in the lateral portion of the ventromedial nucleus. Effects of 5 micrograms of EB were evaluated at 1.5, 6, 12 and 45 h after administration. No changes were noted at 1.5 h, but 5-HIAA in the ventromedial nucleus was elevated at 6 and 12 h. NE levels were elevated at 12 and 45 h in the diagonal band and preoptic nuclei and at 45 h in the lateral septum and periventricular area of the hypothalamus. DA levels decreased in the arcuate-median eminence area 45 h after estrogen. Intravenous administration of 10 micrograms of estrogen and measurement of monoamines 1 h later was not associated with altered levels of any monoamine suggesting that the estrogen-dependent changes are consistent with the genomic model for steroid hormone action.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗