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K Kolasa

Publications and source records attributed to K Kolasa.

At least 19 recordsLinked to original sources

Hippocampal sympathetic ingrowth occurs following 192-IgG-Saporin administration.

Electrolytic lesions of the medial septal region leads to an unusual neuronal reorganization in which peripheral sympathetic fibers, originating from the superior cervical ganglia, grow into the cholinergically denervated areas of the hippocampus. Since these lesions disrupt cells and fibers of passage which are non-cholinergic, there has been a debate whether Hippocampal Sympathetic Ingrowth is due only to cholinergic denervation of the hippocampus. Using the intraseptal administration of 192-IgG-Saporin, a specific cholinergic neurotoxin, we have found that hippocampal sympathetic ingrowth occurs in the cholinergically denervated hippocampus at 4, 8 and 12 weeks post Saporin injection. These results clearly suggest that hippocampal sympathetic ingrowth is due to the specific loss of the cholinergic projection from the medial septum.

Acetylcholine↗

Effects of pertussis toxin and galpha-protein-specific antibodies on phosphoinositide hydrolysis in rat brain membranes after cholinergic denervation and hippocampal sympathetic ingrowth.

Cholinergic denervation of the hippocampal formation, via medial septal lesions, induces peripheral noradrenergic fibers, originating from the superior cervical ganglion, to grow into the hippocampus. We have previously reported that cholinergic denervation and hippocampal sympathetic ingrowth differentially affect guanosine-5'-O-(3-thiotriphosphate)- as well as guanosine-5'-O-(3-thiotriphosphate) + carbachol-stimulated polyphosphoinositide hydrolysis, suggesting an alteration in G proteins and/or the entire receptor complex. To examine the type of G protein which may be involved in these effects, rat dorsal hippocampal membranes were preincubated with pertussis toxin in the presence of guanosine-5'-O-(3-thiotriphosphate) and guanosine-5'-O-(3-thiotriphosphate) + carbachol. Pertussis toxin reduced guanosine-5'-O-(3-thiotriphosphate) in all groups, while guanosine-5'-O-(3-thiotriphosphate) + carbachol-stimulated phosphoinositide hydrolysis was reduced in controls and animals without sympathetic ingrowth but not in animals with hippocampal sympathetic ingrowth. This suggests that pertussis toxin-sensitive G proteins may be involved in the mediation of phosphoinositide hydrolysis. To confirm this hypothesis, membranes were preincubated with antibodies to Galphao and Gq/11. The Go antibody significantly decreased guanosine-5'-O-(3-thiotriphosphate) in all groups, while guanosine-5'-O-(3-thiotriphosphate) +carbachol-stimulated phosphoinositide hydrolysis was reduced only in hippocampal sympathetic ingrowth. Impairment of guanosine-5'-O-(3-thiotriphosphate) and carbachol-stimulated phosphoinositide hydrolysis was also decreased in all groups when preincubated with Gq/11 antibody. To determine whether hippocampal sympathetic ingrowth or cholinergic denervation altered the concentration of various G proteins, immunoblotting methodology was utilized. Gq/11 concentrations were found to be equivalent among groups. The density of Go1, Go2, and Go3 isoforms was significantly increased in the cholinergic denervation, while in the hippocampal sympathetic ingrowth only group Go3 was significantly increased. When assessed as total Go protein, density was increased significantly only in the cholinergic denervation group. Overall, these results suggest that hippocampal sympathetic ingrowth and cholinergic denervation induce alterations in phosphoinositide hydrolysis through both the Gq/11 and the Go proteins and that the coupling between muscarinic receptor and G protein is the possible site which affects changes in phosphoinositide turnover. Our results also suggest that cholinergic denervation and hippocampal sympathetic ingrowth may mediate phosphoinositide hydrolysis through an effect on different isoforms of the same G protein.

Animals↗

Effect of phospholipase C and protein kinase C following cholinergic denervation and hippocampal sympathetic ingrowth in rat hippocampus.

Following cholinergic denervation of the hippocampus by medial septal lesions, an unusual neuronal reorganization occurs in which peripheral adrenergic fibers arising from the superior cervical ganglia grow into the hippocampus (hippocampal sympathetic ingrowth). We have reported previously that cholinergic denervation and hippocampal sympathetic ingrowth differentially affected cholinergically stimulated phosphoinositide hydrolysis, concentration and affinity of muscarinic receptors, Go-protein level and protein kinase C activity. To complete these studies, we determined whether cholinergic denervation and hippocampal sympathetic ingrowth influenced phospholipase C and protein kinase C expression in dorsal hippocampal membranes and cytosol. Using immunoblotting methods, the results showed that the 100,000 mol. wt subunit of phospholipase Cbeta was increased in the membrane fraction in the hippocampal sympathetic ingrowth group by 45% compared to controls and the 150,000 mol.wt subunit was increased by 75% and 59% compared to controls and cholinergic denervation, respectively. For protein kinase C detection, immunoblots were prepared using antibodies selective for "classical" protein kinase C members (alpha, beta, gamma) and for the "novel" protein kinase C subfamily members (delta, θ). Membrane protein kinase Cbeta was decreased in hippocampal sympathetic ingrowth by 35% compared to controls and by 41% compared to cytosolic hippocampal sympathetic ingrowth. Membrane protein kinase Cbeta was decreased in cholinergic denervation by 28% compared to controls. When compared to membranes from controls and the cholinergic denervation group, and to cytosolic fractions from the hippocampal sympathetic ingrowth groups, respectively, the following membrane protein kinase isoforms were found to be decreased by hippocampal sympathetic ingrowth: gamma by 55%, 40% and 57%; delta by 91.5%, 70% and 120%; theta; by 95%, 100% and 86%.In conclusion, our results may indicate the connection between the previously reported differential influence of hippocampal sympathetic ingrowth and cholinergic denervation on cholinergically stimulated phosphoinositol hydrolysis. The "normalization" of phosphoinositol hydrolysis found in hippocampal sympathetic ingrowth may be due to the increase in phospholipase Cbeta expression in hippocampal sympathetic ingrowth membrane fractions. Since the activation of protein kinase C is known to block phosphoinositol hydrolysis, hippocampal sympathetic ingrowth "normalization" of phosphoinositol hydrolysis may result from a reduction in protein kinase expression in hippocampal sympathetic ingrowth membranes.

Animals↗

Apoptotic protein expression and activation of caspases is changed following cholinergic denervation and hippocampal sympathetic ingrowth in rat hippocampus.

Following cholinergic denervation of the hippocampus by medial septal lesions, an unusual neuronal reorganization occurs in which peripheral adrenergic fibers arising from superior cervical ganglia grow into the hippocampus (hippocampal sympathetic ingrowth). Recent studies suggest that a similar process, in which sympathetic noradrenergic axons invade the hippocampus, can occur in Alzheimer's disease patients. In the last few years, the occurrence of apoptotic cell death has been studied in Alzheimer's disease patients and in animal models of this disorder. Several studies suggest that the hippocampus is an important area to be considered for apoptotic cell death. In our studies in the rat hippocampus, we have measured the expression of inducers and blockers of apoptosis in membrane, cytosolic and mitochondrial fractions, and the activity of caspases. The level of cytosolic Fas was increased in cholinergic denervation compared to control and hippocampal sympathetic ingrowth groups. The membrane Fas ligand expression was significantly increased in hippocampal sympathetic ingrowth and in cholinergic denervation compared to the control group. The level of caspase-3 (CPP32) was increased in the cholinergic denervation group compared to control and hippocampal sympathetic ingrowth groups. The cytosolic expression of bcl-x was increased in hippocampal sympathetic ingrowth compared to control and cholinergic denervation. The cytosolic activity of caspase-3 appeared to be significantly decreased in hippocampal sympathetic ingrowth and increased in cholinergic denervation groups compared to control and cholinergic denervation/hippocampal sympathetic ingrowth, respectively. From the present results, we suggest that cholinergic denervation may be responsible for pro-apoptotic responses, while hippocampal sympathetic ingrowth may protect neurons from apoptosis in rat dorsal hippocampus.

Alzheimer Disease↗

Virtual seminars for disseminating medical nutrition education curriculum ideas.

There is a need and a desire for educators working toward implementation of nutrition in medical schools and residency programs to share ideas and materials. The World Wide Web enables computer-mediated communications through which a medical nutrition curriculum could be discussed; however, existing formats lack focus and structure. In January 1999, a virtual seminar that focused on nutrition education in medical schools and residency programs was conducted. The seminar, titled "Making Room for Nutrition Education, was sponsored by organizations that have active medical nutrition educators. The seminar included 5 topics discussed over a 4-d period. The transcript was made available at http://www.preventivenutrition. com. There were 119 registered participants. Responses to a postseminar questionnaire were positive; there was interest in an ongoing series of virtual seminars.

Curriculum↗

Primary care providers need a variety of nutrition and wellness patient education materials.

OBJECTIVE: To assess and document the need for nutrition and wellness patient education materials. DESIGN: The results of open-ended interviews and focus groups were used to develop a mail-type survey. The 46-item survey addressed barriers to using nutrition and wellness education materials as well as format, education/reading level, foreign languages, and topics needed. North Carolina Cooperative Extension Service (NCCES) family and consumer education agents distributed surveys to family and general practices throughout North Carolina. SUBJECTS: Of the 721 primary care providers surveyed, 303 (42%) returned usable surveys. Respondents practiced in 89 of the 100 counties of the state served by NCCES family and consumer education agents. STATISTICAL ANALYSIS PERFORMED: Descriptive statistics and independent sample t tests were used to analyze survey results. RESULTS: Limited time with patients and inability to obtain materials because of cost or being unsure of sources were most often identified as barriers to using nutrition and wellness materials. Of the 26 topics surveyed, 6 had mean levels of need greater than or equal to high need (mean score > or = 4): weight control for adults, smoking cessation, changing dietary fat intake, exercise guidelines for healthy adults, general stress management guidelines, and healthful eating for older adults. Twenty-four of the 26 topics had mean levels of need greater than or equal to moderate need (mean score > or = 3). Topics with moderate need included guidelines for overweight children and adolescents, nutrition for chronic disease prevention, and healthful eating for various stages of the life cycle. The combined mean score for topics dealing with weight control and exercise for adults, adolescents, and children was greater than the score for high need (mean score > 4). Eighty-three percent of respondents preferred 1-page, printed handouts. Forty-five percent requested materials in Spanish. APPLICATIONS: Dietitians who work in a variety of settings can use techniques similar to those described here to determine the patient education materials practitioners need for the populations they serve. The information obtained from this study will be used to develop 1-page, printed handouts. A registered dietitian and a food and nutrition specialist with NCCES will develop and pilot-test the handouts. These materials will be made available to primary care providers in North Carolina via local NCCES family and consumer education agents, many of whom are registered dietitians.

Data Collection↗

Effect of hippocampal sympathetic ingrowth and cholinergic denervation on hippocampal phospholipase C activity and G-protein function.

Following cholinergic denervation of the hippocampal formation, via medial septal lesions, peripheral noradrenergic fibers, originating from the superior cervical ganglion, grow into the hippocampus. In previous studies, we have found that hippocampal sympathetic ingrowth and cholinergic denervation alone (animals with concurrent medial septal lesions and superior cervical ganglionectomy) alter phosphoinositide turnover and muscarinic cholinergic receptors in such a way as to suggest an alteration in coupling between the muscarinic cholinergic receptors and phosphoinositol turnover. To test this hypothesis we examined the effect of hippocampal sympathetic ingrowth and cholinergic denervation on phospholipase C activity, G-protein function and the whole receptor complex by measuring the amount of phosphoinositide hydrolysed in hippocampal membranes of the rat. Neither hippocampal sympathetic ingrowth nor cholinergic denervation was found to alter phospholipase C activity when activated by increasing concentrations of Ca2+. In dorsal hippocampus, cholinergic denervation, when compared to hippocampal sympathetic ingrowth and controls, was found to decrease the amount of phosphoinositol hydrolysed when stimulated with the GTP analog, guanosine-5'-O-(3-thiotriphosphate). When guanosine-5'-O-(3-thiotriphosphate) plus carbachol (1 mM) was utilized to stimulate the entire receptor complex, phosphoinositol hydrolysis was found to be decreased in the cholinergic denervation group as compared to both hippocampal sympathetic ingrowth and control groups. This effect was maximum at 3 microM guanosine-5'-O-(3-thiotriphosphate). These results suggest that both hippocampal sympathetic ingrowth and cholinergic denervation affect the efficiency of coupling between the muscarinic cholinergic receptors and phosphoinositol turnover, with cholinergic denervation decreasing and hippocampal sympathetic ingrowth "normalizing" efficiency. Further, they suggest that the G-protein is the site at which hippocampal sympathetic ingrowth and cholinergic denervation mediate their effects. The results of these experiments are also discussed within the context of recent findings demonstrating G-protein abnormalities in Alzheimer's disease.

Adrenergic Fibers↗

Cholinergic denervation and sympathetic ingrowth result in persistent changes in hippocampal muscarinic receptors.

Our laboratory has been utilizing the model of hippocampal sympathetic ingrowth, which has been suggested to occur in Alzheimer's disease, to investigate the effects of cholinergic denervation and hippocampal rearrangements. After cholinergic denervation by medial septal lesions, peripheral sympathetic fibres originating from the superior cervical ganglia grow into the rat hippocampus. This hippocampal sympathetic ingrowth can be prevented by superior cervical ganglionectomy. We examined the long-term effects of these treatments on muscarinic receptors by comparing [3H]quinuclidinyl benzilate binding in rat dorsal hippocampus four and 12 weeks post lesion. Four groups of animals were employed, including controls (sham lesion+sham ganglionectomy), animals with ingrowth (medial septal lesion+ sham ganglionectomy), animals with cholinergic denervation alone (medial septal lesion+ ganglionectomy), and ganglionectomy alone (sham lesion+ganglionectomy) animals. In dorsal hippocampus four weeks post lesion, binding affinity was similar among all groups, while muscarinic receptor number was increased in ingrowth animals as compared to both the control (P<0.0002) and ganglionectomy animals (P<0.01). By 12 weeks, receptor affinity was significantly decreased in ingrowth (P<0.0001) and cholinergic denervation (P<0.0003) groups, and receptor number remained significantly elevated in ingrowth animals as compared to control (P<0.01), ganglionectomy (P<0.02) and cholinergic denervation (P<0.01) groups. The decrease in muscarinic receptor affinity may provide some insight into the ineffectiveness of cholinomimetic therapies in Alzheimer's disease, in that agonist efficacy would be reduced at the receptor.

Animals↗

Sympathetic sprouting reverses decreases in membrane-associated activity of protein kinase C following septohippocampal denervation of the rat hippocampus.

Hippocampal sympathetic ingrowth (HSI), a form of neuronal plasticity, is induced by medial septal lesions and consists of the sprouting of peripheral sympathetic fibers, arising from the superior cervical ganglion, into the dentate gyrus and CA3 region of the hippocampus. HSI has been previously shown to alter learned and spontaneous behaviors, phosphatidyl inositide hydrolysis, and the antagonist binding kinetics of both muscarinic cholinergic receptors and phorbol ester receptors. We now report that sympathetic sprouting reverses decreases in membrane-associated activity of protein kinase C (PKC) following septohippocampal denervation of the rat hippocampus. Further, no changes were found in alpha, beta or gamma PKC isoenzymes among experimental groups, suggesting that the group A PKC isoforms do not mediate the observed changes in activity and phorbol ester binding.

Analysis of Variance↗

The effect of hippocampal sympathetic ingrowth and cholinergic denervation on hippocampal M2 cholinergic receptors.

After cholinergic denervation of the hippocampus, via medial septal (MS) lesions, peripheral sympathetic fibers, originating from the superior cervical ganglia, grow into the hippocampus. In this study, we sought to determine the effect of hippocampal sympathetic ingrowth (HSI) on the M2 subtype of muscarinic cholinergic receptors, by examining the membrane binding of [3H]AF-DX 384 in hippocampal tissue from control rats, rats with HSI and rats with MS lesions + concurrent ganglionectomy (CD group). In dorsal hippocampus, Kd was found to be increased while Bmax was decreased in the CD group as compared with both the HSI and control group which did not differ from one another. In ventral hippocampus, Kd was found to be increased while Bmax was decreased in the CD group when compared only with the control group. These results suggest that sympathetic ingrowth, which has its greatest concentration in dorsal hippocampus, can 'normalize' the M2 receptor in hippocampus.

Animals↗

Hippocampal sympathetic ingrowth and cholinergic denervation uniquely alter muscarinic receptor subtypes in the hippocampus.

Following cholinergic denervation of the hippocampus by medial septal lesions, and unusual neuronal reorganization occurs, in which peripheral sympathetic fibers, originating from the superior cervical ganglia, grow into the hippocampus. Previously, we have found that both hippocampal sympathetic ingrowth (HSI) and cholinergic denervation (CD), alone, altered the total number and affinity of muscarinic cholinergic receptors (mAChR). In this study, we utilized the muscarinic antagonist [3H]Pirenzepine, in combination with membrane radioligand binding techniques, to determine the effects of HSI and CD on hippocampal M1 and M1 + M3 mAChR subtypes, 4 weeks after MS lesions. In both the dorsal and ventral hippocampus, HSI was found to markedly diminish the number of M1 AChRs, while CD was found to increase the number of M1 AChRs. Neither treatment affected the affinity of the M1 AChR. However, when M1 + M3 binding was assessed, CD was found to decrease the affinity in both hippocampal regions, without altering the number of receptors. Neither affinity nor number of M1 + M3 receptors was altered by HSI. The results of this study suggest that both cholinergic denervation and hippocampal sympathetic ingrowth uniquely affect hippocampal muscarinic receptors.

Acetylcholine↗

The effect of cholinergic denervation and hippocampal sympathetic ingrowth on the internalization of muscarinic receptors in rat hippocampus.

Following cholinergic denervation of the hippocampus by medial septal (MS) lesions, an unusual neuronal reorganization occurs in which peripheral sympathetic fibers, originating from the superior cervical ganglia, grow into the hippocampus (hippocampal sympathetic ingrowth; HSI). Previously, we have found that with MS lesions, animals with (the HSI(+) group) and without (HSI(-) group) ingrowth differed in carbachol stimulated PI hydrolysis, in PKC activity, and in muscarinic cholinergic receptors (mAChR). In this study, performed in hippocampal slices obtained four weeks after MS lesions, we utilized the hydrophilic muscarinic antagonist [3H]N-methylscopolamine ([3H]NMS) and hydrophobic muscarinic antagonist [3H]quinuclidinyl benzilate ([3H]QNB) in the presence of either 4-alpha-phorbol or phorbol 12,13-dibutyrate (PDBu) to determine the effect of MS lesions with and without ingrowth on PKC-mediated mAChR internalization. In the presence of PDBu, a group effect was observed in [3H]NMS binding, with control groups > HSI(+) group > HSI(-) group. However, [3H]QNB binding was similar across groups. These results suggest that the cholinergic denervation of the hippocampus enhances the internalization of mAChRs, which is modified in the presence of HSI.

Acetylcholine↗

Community perceptions of adolescent health and sexuality. Results from a southern community-based project.

OBJECTIVE: To describe the attitudes about adolescent health issues, especially school-based health services, held by adults in a rural community. DESIGN: "Before-after," quasi-experimental design involving independent, cross-sectional population-based surveys in 1989 and 1992. SETTING: Rural county located in the southeastern United States. PARTICIPANTS: Probability sample of adults, 18 years and older, who were residents of the county, including 831 respondents in the first survey and 210 respondents in the second survey. INTERVENTION: County-wide public education campaign involving public service announcements on television and radio, newspaper advertisements, posters, and open-to-the-public adolescent health programs and events. MAIN OUTCOME MEASURES: Attitudes about the types of health services that should be included in a public school-based adolescent health program. RESULTS: Rural adults' attitudes toward public school-based adolescent health services were similar before and after the community-wide campaign. Respondents believed the public schools should provide teenagers with information and counseling on substance abuse, sexual activity, birth control, and the acquired immunodeficiency syndrome but should not provide primary health care or birth control products. Most adults believed that sex and acquired immunodeficiency syndrome education should begin before high school. CONCLUSIONS: A comprehensive, public school-based adolescent health program providing health information but not health services may be acceptable to this community. Adults' attitudes about adolescent health issues do not appear to have been modified by the adolescent health awareness campaign.

Adolescent↗

Behavioral and biochemical changes after bilateral electrolytic lesions of the red nucleus of rat.

Bilateral electrolytic lesions of the red nucleus (RN) of rat decreased apomorphine-induced stereotypy, increased haloperidol-induced catalepsy, reversed apomorphine-induced hypothermy, decreased spiroperidol-induced hypomotility, and BHT-920-induced yawning and penile erection episodes. Moreover, apomorphine antagonized haloperidol-induced catalepsy in the RN-lesioned group. The lesioned animals revealed depleted levels of dopamine and its metabolites in brain areas as well as serotonin and its metabolite. The brain areas analyzed were pyriform cortex, substantia nigra, striatum, enthorinal cortex, and cerebellum. Based on these results, it is very likely that the RN has a complex role in the behavior of rats as a consequence of dopaminergic-serotoninergic changes in the central nervous system.

Animals↗

Sexual abstinence counseling of adolescents by physicians.

Attending physicians and residents at a southeastern rural teaching hospital specializing in family practice and pediatrics, as well as local family practice physicians and pediatricians, were surveyed with regard to their counseling of adolescents about sexuality, including abstinence. The physicians were asked to complete an original 67-item questionnaire describing their attitudes and practices. More than 60% of physicians reported regularly addressing the issues of HIV, STD, pregnancy prevention, and responsible sexual behaviors. About 35% of the physicians reported regularly counseling adolescents regarding 17 other issues pertaining to pregnancy and disease prevention, sexual abuse, or related medical aspects of sexuality. No respondents felt "very effective" in their counseling. Some agree they would be helped by additional training.

Adolescent↗

Synergistic activation of phosphoinositide hydrolysis induced in brain slices by norepinephrine and the excitatory amino acid agonist, trans-ACPD.

Norepinephrine and trans-1-aminocyclopentyl-1,3-dicarboxylic acid (ACPD) each individually stimulated hydrolysis of phosphoinositides and when tested in combination caused a stimulation that was 50-90% greater than additive in hippocampal and cortical slices of the rat but not in striatal slices. This synergistic augmentation of hydrolysis of phosphoinositide was evident with all stimulatory concentrations of norepinephrine and of ACPD up to 1 mM, at which point ACPD was inhibitory. A time-course study revealed no lag in the synergistic interaction and no down-regulation through 60 min of incubation of the augmented response to the combined agonists. The synergistic reaction was mediated by alpha 1-adrenergic receptors and by metabotropic excitatory amino acid receptors. Increased intracellular calcium, but not activation of protein kinase C, may play a role in mediating the synergistic interaction. Thus, a unique synergistic stimulatory interaction was found between two receptors coupled with phosphoinositide metabolism, a finding which also supports the suggestion that these two systems are co-localized in some cells.

Animals↗