Biomedical subjects

B Oderfeld-Nowak

Publications and source records attributed to B Oderfeld-Nowak.

At least 19 recordsLinked to original sources

PubMed1995

Bilateral gliosis in unilaterally lesioned septohippocampal system: changes in GFAP immunoreactivity and content.

Unilateral damage to the lateral fimbria led to a bilateral gliosis in the septum and hippocampus. The gliosis was manifested by an increase in GFAP staining, accompanied by an increased number of glial fibrillary acidic protein (GFAP)(+) cells and GFAP content; the latter however was not visible in the contralateral septum. In general, the contralateral reaction appeared weaker than the ipsilateral one. The pattern of contralateral increase in GFAP-immunoreactivity (IR) matched almost exactly that observed on the ipsilateral side in the hippocampus (the most evident increase was seen in the oriens and pyramidal layers of cornu Ammonis 3 and in polymorphic area of gyrus dentatus). In the septum the bilateral increase in GFAP-IR was mainly visible in the dorsolateral quadrant of the structure; however in the ipsilateral side it spread over the whole half of the structure. The astrocytic responses in the septum and hippocampus were not equivalent: they differed mainly with regard to the increase of GFAP(+) cells (over 300% of control in the anterior part of the septum and only about 120% in the dorsal hippocampus). The differences between the percentage increases of other gliotic indices: GFAP-IR and GFAP content. Various possibilities that may account for the occurrence of contralateral gliosis are discussed, the most plausible being the contribution of interhemispheric and intraseptal links and the action of some diffusible agents. We suggest that bilateral gliosis may have an impact on compensatory postlesion processes, possibly by providing trophic support to impaired neurons.

Animals↗

PubMed1993

Differential effects of GM1 ganglioside treatment on glial fibrillary acidic protein content in the rat septum and hippocampus after partial interruption of their connections.

The glial fibrillary acidic protein (GFAP) content was investigated using immunoblotting techniques in the septum and hippocampus of the rat after bilateral lateral fimbria transection. Seven days after surgery GFAP content increased significantly both in the septum (140% of control) and hippocampus (120% in dorsal, the less denervated, and 145% in the most denervated ventral part), indicating the occurrence of reactive gliosis. The GM1 treatment caused statistically significant attenuation of GFAP increment in all hippocampal parts. In contrast, GM1 treatment has no influence on the increase of GFAP content in the septum. Results suggest a differential effect of GM1 on the two gliotic reactions formed as a consequence of the lesion at the level of the source of innervation (septum) and the target (hippocampus).

Animals↗

PubMed1992

In vivo activated brain astrocytes may produce and secrete nerve growth factor-like molecules.

The cellular localization of the nerve growth factor-like immunoreactivity (NGF-LIR) has been studied in the septum and hippocampus of the rat brain 7 days following partial electrolytic lesion (2 mA, 30 s) of the septohippocampal pathways or after single intraventricular administration of 15 U of interleukin-1 beta (IL-1 beta). A double immunostaining technique which allowed a simultaneous localization of NGF-LIR and that of astroglia marker glial fibrillary acidic protein was used. Our data show that after both treatments, apart from neuronal localization of NGF-LIR typical for normal brain, many astrocytes both in the septum and hippocampus became NGF-like immunoreactive. Besides, NGF-LIR often formed a "halo" reaction around astrocytes. These results support the notion that activated in vivo brain astrocytes may, just as astrocytes growing in vitro, synthesize and secrete NGF-like molecules. Our findings may be of importance in considerations concerning trophic support to the cholinergic neurons of the basal forebrain nuclei whose impaired function is essentially responsible for some cognitive deficits in neurodegenerative diseases such as Alzheimer disease.

Animals↗

PubMed1992

Cellular localization of nerve growth factor-like immunoreactivity in hippocampus and septum of adult rat brain.

The cellular localization of the nerve growth factor-like immunoreactivity (NGF-LIR) has been studied in the intact adult rat brain at the level of the hippocampus and the septum. Immunolabelling for NGF combined with counterstaining with cresyl violet and double immunostaining technique, which allowed simultaneous localization of NGF-LIR and that of astroglial marker -GFAP, were used. The data indicate neuronal localization of NGF-like immunoreactivity and a lack of colocalization of NGF-LIR with the immunoreactivity of GFAP in the hippocampus. These data are consistent with in situ hybridization results for NGF and immunocytochemical results for pro-NGF localization obtained by others. At the septal level, apart from neuronal localization of NGF-LIR, single NGF-like immunoreactive astrocytes have been observed. This suggests that, although to a very small extent, in vivo intact brain astrocytes may, just as astrocytes growing in vitro, synthesize NGF-like molecules. This finding may be of importance in better understanding the trophic support for NGF responsive cholinergic neurones in the brain.

Animals↗

PubMed1990

Derivatives of ganglioside GM1 as neuronotrophic agents: comparison of in vivo and in vitro effects.

Exogenously administered gangliosides have been shown to behave as neuronotrophic/neuritogenic agents in a variety of cell culture systems and animal models, but it is not known whether they operate by the same mechanism in vivo and in vitro. To probe this question we have employed two derivatives of GM1 lacking the negative charge: the methyl ester (GM1-CH3) and the NaBH4 reduction product of the latter (GM1-OH) in which the carboxyl group is replaced by a primary alcohol. Both derivatives proved to be as neuritogenic as GM1 in 3 cell culture systems: neuro-2A cels, PC12 cells and explanted dorsal root ganglia. However, GM1-OH proved ineffective when applied to two animal models involving reduction of cholinergic markers in: (a) hippocampus following lesion of the lateral fimbria and (b) nucleus basalis magnocellularis following cortical lesion; GM1-CH3 showed marginal activity in (a) but more in (b), possibly owing to slow hydrolysis to GM1 which was highly active in both animal models. These results indicate the necessity of a negative change on the ganglioside molecule for in vivo but not in vitro activity and point to different mechanisms for the trophic effects of exogenous gangliosides.

Animals↗

PubMed1990

Gangliosides offer partial protection in experimental allergic neuritis.

The effect of gangliosides on the clinical course of experimental allergic neuritis was tested in Lewis rats sensitized with bovine intradural root myelin in complete Freund's adjuvant. A mixture of bovine brain gangliosides (GM1, GD1a, GD1b, GT1b) was injected intramuscularly at a daily dose of 20 mg per kilogram of body weight, beginning 6 days after inoculation. The results from seven different experiments show that in most cases, the administered gangliosides were partially protective. Particularly striking was the reduction in mortality rate to half or less of saline-injected controls. Cumulative clinical index scores were also significantly lower with ganglioside treatment in five of the seven experiments. The cause of the wide variability is not known, but it was noted that better results were obtained when the animals were sensitized with freshly isolated myelin.

Animals↗

PubMed1990

Differential response of subtypes of 5-HT1 recognition sites in the rat hippocampus to partial denervation.

[3H]5-HT uptake and [3H]5-HT binding to 5-HT1 receptor subtypes (5-HT1A and non-5-HT1A sites, having high and low affinity to spiperone, respectively) were studied in the rat hippocampus ten days after two types of electrocoagulative lesions. The lesion of supracallosal area and subtotal lesion of the septum destroy supra- and subcallosal hippocampal afferents, respectively. Both types of afferents carry serotonergic fibers to the hippocampus. A significant decrease of [3H]5-HT uptake (by about one half of the control) was observed after both lesions. [3H]5-HT binding to 5-HT1A sites, comprising ca 60% of the total number of 5-HT1 sites, remained unchanged after both lesions, while the binding to non-5-HT1A sites decreased significantly (by ca 20%) but only after the lesion of the septum. The results point to a postsynaptic localization of 5-HT1A and of the bulk of non-5-HT1A sites; the decrease of the proportion of non-5-HT1A sites after septal lesion may be due to their presynaptic localization on the subcallosal pathway and/or may reflect receptor alterations in consequence of transsynaptic events in the hippocampus caused by septal lesion. Differential response of serotonin receptor subtypes to lesions of supracallosal and septal areas may underlie the differential functional responses to those lesions.

Afferent Pathways↗

PubMed1990

Nerve growth factor induces a dose-dependent and long-lasting increase of choline acetyltransferase activity in the septal area and hippocampus of uninjured rats.

The effect of nerve growth factor (NGF) on the intact septohippocampal cholinergic system of adult rats was studied. Nerve growth factor was continuously infused at different doses (5-100 micrograms) for two weeks into the lateral ventricle of adult rats. Controls received intracerebroventricular infusion of equal amounts of cytochrome c. Nerve growth factor treatment was capable of inducing a dose-dependent increase of choline acetyltransferase activity (ChAT) in septal area and ventral hippocampus. In both areas, the NGF-induced rise of ChAT activity was sustained for at least one week after infusion, then it progressively declined towards control values. By three and five weeks, using NGF at 25 and 100 micrograms respectively, ChAT increase was still significant in both septum and ventral hippocampus. The present findings corroborate a role for NGF in adult septohippocampal cholinergic system and indicate that the "pharmacological" modulation of these neurons by NGF may last several weeks following withdrawal of this trophic factor.

Animals↗

PubMed1990

Gangliosides as neurotrophic agents: studies on the mechanism of action.

During the normal course of neuronal differentiation gangliosides undergo marked changes in both quantity and quality. These changes, i.e. several-fold increase in concentration and appearance of the gangliotetraose family, have been observed both in vivo and in neuronal cell cultures. In addition to these naturally occurring (endogenous) manifestations, exogenously administered gangliosides have been observed to exert neuritogenic and/or neuronotrophic effects on a variety of neuroblastoma cell lines and primary neuronal culture systems. Unlike the endogenous effects, which appear to require gangliotetraose structures, the structural specificity of the exogenous effect is quite broad. Thus, all of 11 different gangliosides proved neuritogenic with neuro-2A neuroblastoma cells. Furthermore, synthetic sialoglycolipids possessing a beta-ketosidic sialic acid linkage and/or a glyceride-like moiety in place of ceramide all caused enhanced neurite outgrowth in neuro-2A, PC12, and embryonic chick dorsal root ganglia. A derivative of GM1 lacking the negative charge was also active in the same 3 systems. These results point to general perturbation of the membrane, probably a physical-chemical effect, in a manner which triggers intracellular events leading to differentiation. In contrast to these in vitro results, use of the above GM1 derivative in two in vivo models proved ineffective in maintaining the level of cholinergic markers that were preserved by GM1 in lesioned brains. These results point to fundamentally different mechanism for the trophic effects of administered gangliosides in vivo and in vitro.

Animals↗

PubMed1990

Gangliosides improve the outcome of experimental allergic neuritis (EAN).

The effect of gangliosides on the clinical expression of experimental allergic neuritis (EAN), a PNS counterpart of experimental allergic encephalomyelitis (EAE), was tested in Lewis rats sensitized with bovine intradural root myelin in complete Freund's adjuvant (CFA). A mixture of bovine brain gangliosides (GM1, GD1a, GD1b, GT1b) was injected intramuscularly at a daily dose of 20 mg per kg beginning 6 days post inoculation. The results show that GA treatment considerably reduces the incidence of mortality, delays its occurrence, and reduces the severity of clinical scores when either the whole population or survivors only are considered. Benefit from GA treatment appeared roughly proportional to disease severity. The neuronotrophic and anti-inflammatory effects possibly play a role in GA protecting effect.

Analysis of Variance↗

PubMed1989

Nerve growth factor affects uninjured, adult rat septohippocampal cholinergic neurons.

The effect of nerve growth factor on the intact versus injured septohippocampal cholinergic system of adult rats was studied. Nerve growth factor was continuously infused into the lateral ventricle of adult uninjured rats or rats that had received unilateral partial transection of the fimbria. Controls (operated and unoperated) received intraventricular infusion of cytochrome c. After 2 weeks of nerve growth factor or cytochrome c treatments, choline acetyltransferase and acetylcholinesterase activities were measured in the septal area and in the hippocampus (divided into dorsal, medial and ventral parts). The continuous infusion of nerve growth factor resulted in a marked dose-dependent increase of choline acetyltransferase activity in both septum and hippocampus of adult unlesioned rats. In lesioned rats the nerve growth factor treatment was capable of inducing choline acetyltransferase activity in the hippocampus of not only the lesioned but also the unlesioned side, as well as in the septal area. In addition, nerve growth factor affected choline acetyltransferase activity differently in the hippocampus of the operated side with respect to the contralateral side or in unoperated animals. The chronic infusion of nerve growth factor did not affect acetylcholinesterase activity in the septum or in the hippocampus of either lesioned or unlesioned rats. The present findings indicate that nerve growth factor is capable of modulating the function of not only damaged but also normal adult forebrain cholinergic neurons. This suggests that nerve growth factor may modulate the function of these neurons in adulthood.

Acetylcholinesterase↗

PubMed1987

Analysis of the time course of GM1 ganglioside effect on changes in choline acetyltransferase activity in partially denervated rat hippocampus.

The effect of chronic GMl ganglioside administration (30 mg/kg, daily) for 6, 21, 42 and 90 days on the activity of choline acetyltransferase was investigated in the hippocampus of rats with partial electrolytic lesions of the dorsal hippocampal afferents and in unoperated rats. No influence of GM1 administration on ChAT activity was noted in unoperated animals. The lesions caused denervation in the hippocampus, which occurred with varying intensity along its dorsoventral axis, as shown by the gradual pattern of decrease in ChAT activity. GM1 counteracted the decline in enzyme activity, however the intensity of this influence diminished with the time after surgery. A positive correlation between the GM1 effectiveness and the degree of denervation at early postsurgical stages (6, 21 days) was found, which may be ascribed to the appearance of neuronotrophic factors at this period, proportional to the severity of damage. We suggest that the decline of the GM1 effectiveness is due to a decrease in trophic activity, and/or the development of spontaneous recovery

Afferent Pathways↗

PubMed1987

Differential response of hippocampal muscarinic cholinergic receptors to various deafferentations of the hippocampus in the rat.

The influence of bilateral electrolytic lesions of different parts of the septum on muscarinic receptor binding in the hippocampus was studied within 14-21 days after operation. The effect of total septal lesion upon receptor binding was also investigated separately in the dorsal and ventral hippocampus and in five consecutive hippocampal parts along the septotemporal axis of the structure. The data indicate that: (i) differential response of muscarinic receptors, as revealed by a decrease, increase or lack of changes in the [3H]QNB binding depends on the site and extent of the lesion, (ii) lack of changes in muscarinic receptor binding can be spurious when the investigation is performed on the whole hippocampus, and masked by regional response differences, (iii) differential response of [3H]QNB binding sites in distinct parts of the hippocampus to total septal lesion may depend on the preexisting differences in the density of cholinergic innervation and of muscarinic receptors.

Acetylcholinesterase↗

PubMed1986

The effect of GM1 ganglioside on cholinergic and serotoninergic systems in the rat hippocampus following partial denervation is dependent on the degree of fiber degeneration.

The partial lesion paradigm of the dorsal hippocampal afferents in the rat was used as a model to study the effect of GM1 ganglioside treatment on recovery of neurotransmitter markers of the cholinergic and serotoninergic activity in various hippocampal regions. It was found that the enhancement of recovery of acetylcholinesterase, choline acetyltransferase and serotonin uptake by GM1 treatment (30 mg/kg i.m., daily), as studied on the 6th and 21st postlesion day, was dependent on the degree of fiber degeneration. The results may be interpreted in terms of the relationship between the action of GM1 and that of neuronotrophic factors whose release also depends on the extent of the fiber degeneration. These data indicate that GM1 elicits the recovery of biochemical parameters, or fails to, depending on the specificity of the trauma. The result may explain why, after certain brain lesions, GM1 does not promote functional recovery.

Acetylcholinesterase↗

PubMed1984

Effect of GM1 ganglioside treatment on postlesion responses of cholinergic enzymes in rat hippocampus after various partial deafferentations.

The effect of intramuscular administration of monosialoganglioside (GM1) on postlesion responses of choline acetyltransferase and acetylcholinesterase activity in partially deafferented rat hippocampus was studied at various survival times. Lesions partially destroying the medioventral, septal area, or lesions performed in supracallosal stria including corpus callosum and cingulum evoked cholinergic denervation of the hippocampus, while those made in entorhinal cortex resulted in partial glutamatergic deafferentation. GM1 treatment potentiates the responses of both cholinergic enzymes, independently of whether the partial deafferentation was homo- or heterotypical. These data indicate that GM1 may facilitate the regrowth of new cholinergic nerve terminals. However, an effect on other compensatory processes, especially in the first postoperative period, is also possible.

Acetylcholinesterase↗

PubMed1983

In vitro studies on the effect of beta-carbolines on the activities of acetylcholinesterase and choline acetyltransferase and on the muscarinic receptor binding of the rat brain.

Acetylcholinesterase (acetylcholine acetylhydrolase, EC 3.1.1.7) activity and muscarinic receptor binding of homogenates from several brain structures were inhibited by beta-carbolines. The inhibition was of the noncompetitive type in the case of the enzyme and of the mixed type in the case of the receptor binding. This effect was most strongly manifested by pyridoindoles(harmane, norharmane), i.e., carbolines containing an aromatic C ring than by the corresponding piperidoindoles (tetrahydroharmane, tetrahydronorharmane), i.e., those with a reduced C ring. The activity of choline acetyltransferase (acetyl-CoA:choline O-acetyltransferase, EC 2.3.1.6) was not altered. These data are further evidence of the interactions between indoleamine derivatives and the cholinergic system. The results are discussed in terms of their possible biological significance.

Acetylcholinesterase↗

PubMed1982

The stimulating effect of ganglioside injections on the recovery of choline acetyltransferase and acetylcholinesterase activities in the hippocampus of the rat after septal lesions.

The effect of intramuscular administration of a mixture of gangliosides (21% GM1, 39.7% GD1a, 16% GD1b, 19% GT1) in a daily of 50 mg per kg upon the time course of changes in hippocampal acetylcholinesterase and choline acetyltransferase activities after extensive medioventral septal lesions in the rat was checked on days 3, 5, 18 and 50 after the operation. Following the early decrease in the enzyme activities to about 25% of control due to degeneration, a gradual recovery up to about 50% of control activity at the 50th day was found. When gangliosides were administered, the recovery in the activity of both enzyme was more pronounced. The ratio of the enzyme activities from the animals injected with gangliosides to that from uninjected animals was 1.45 and 1.48 on the 18th day and 1.62 and 1.50 on the 50th day after the operation, for choline acetyltransferase and acetylcholinesterase activity, respectively. Since no significant effect of ganglioside injection was seen at early post-operative times i.e. on days 3 and 5, the effects seen on days 18 and 50 seem to be specifically due to facilitation of the recovery processes and not to retardation of the degeneration processes. Assuming that the spontaneous recovery of cholinergic enzyme activity reflects reinnervation of the hippocampus through collateral sprouting gangliosides would seen to facilitate the regrowth of new cholinergic nerve terminals.

Acetylcholinesterase↗

PubMed1981

Distribution of choline acetyltransferase, acetylcholinesterase, muscarinic receptor binding, and choline uptake in discrete areas of the rat medulla oblongata.

Quantitative measurements were made of choline acetyltransferase (CAT) activity, acetylcholinesterase (AChE) activity and cholinergic muscarinic receptor binding ([3H]QNB) in eight areas of a cross-section of the rat medulla oblongata. A fourth cholinergic parameter, high-affinity choline uptake, was measured in three groups of these areas. CAT, AChE and [3H]QNB binding were found to be highest in the hypoglossal nucleus and the dorsal motor nucleus of the vagus; the lowest value was in the area which contains the inferior olive and the corticospinal tract. The distribution of AChE and CAT activities varied approximately 7- to 10-fold among the eight regions examined, whereas that of the muscarinic receptor varied only about 4-fold. The Na+-dependent high-affinity choline uptake varied approximately 20-fold from the region with the lowest activity (inferior olivary nucleus and corticospinal tract) to that with the highest activity (tissue areas containing the dorsal motor nucleus, hypoglossal nucleus of the solitary tract and nucleus cuneatus). The four cholinergic parameters are statistically correlated throughout all the areas of the medulla which were studied.

Acetylcholinesterase↗