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Biomedical subjects

V Bigl

Publications and source records attributed to V Bigl.

At least 109 records · Page 6Linked to original sources

Effect of monocular deprivation on uptake and binding of [3H]glutamate in the visual system of rat brain.

[3H]Glutamate uptake and binding studies were performed in the visual cortices, lateral geniculate nuclei (LGN), and superior colliculi of 3-month-old rats with one eyelid surgically closed from postnatal day 10 (monocular deprivation). Uptake and binding were highest in the lateral geniculate nucleus followed by the visual cortex (69% and 15%, respectively compared to LGN values) and the superior colliculus (32% and 59% of LGN values). Monocular deprivation did not affect [3H]glutamate uptake in any of the visual regions examined. However, a 46% decrease in [3H]glutamate binding in the lateral geniculate nucleus ipsilateral to the sutured eye was detected. Binding levels in other regions were not affected.

Animals↗

Kinetics of the interaction of dihydroalprenolol with beta-adrenergic receptors in rat cerebral cortex.

Time and temperature dependence of the binding of 3H-dihydroalprenolol (3H-DHA) to beta-adrenergic receptors in rat cerebral cortex is described. The kinetic data obtained suggest that 3H-DHA binding proceeds through a two-step reaction scheme consisting of a bimolecular association step followed by an unimolecular internal conversion of the radioligand receptor complex (isomerisation). Equilibrium thermodynamic analysis provided evidence that the over-all binding process is associated with a small decrease in enthalpy and a substantial increase in entropy. Within the framework of the two-step binding kinetics, the evaluation of the temperature dependence by the van't Hoff analysis resulted in values for thermodynamic parameters for the single equilibrium steps. The data suggest that the association step can be considered as a bimolecular hydrophobic interaction which is mainly entropy-driven due to the release of structural water, while the isomerisation step is accompanied by a large negative change in both enthalpy and entropy. The large negative change in the activation entropy for the forward reaction of the isomerisation step, obtained from evaluation of Arrhenius plots, indicates an internal conversion to a highly ordered receptor-ligand complex, while the low activation energy points to a small threshold energy for reaching this structure. Thus, these result support a previous assumption that the hydrophobic center of an adrenergic antagonist interacts with the receptor by entering a pocket (Cherksey et al. 1981).

Alprenolol↗

Regional distribution of neurotransmitter receptors in the visual structures of the rat brain.

The regional distribution of the binding of 3H-quinuclidinyl benzylate, 3H-dihydroergocryptine, 3H-dihydroalprenolol, 3H-serotonin and 3H-flunitrazepam was investigated in the retina, lateral geniculate nucleus, superior colliculus, visual and frontal cortex of 25-day-old and adult rats. In adult rats the highest binding levels for the muscarinic acetylcholine and benzodiazepine receptor are present in the visual and frontal cortex, whereas alpha- and beta-adrenergic receptor binding was highest in the retina and 3H-serotonin binding in the lateral geniculate nucleus. Binding of 3H-quinuclidinyl benzylate, 3H-flunitrazepam and 3H-serotonin increases in the adult rats, whereas alpha- and beta-adrenergic receptor binding is decreased compared to the binding levels found in 25-day-old animals. The distribution of the neurotransmitter receptors studied within the visual structures cannot be readily correlated with the pattern of some neurochemical presynaptic parameters.

Animals↗

Loss of neurons in the nucleus basalis of Meynert in Alzheimer's disease, paralysis agitans and Korsakoff's Disease.

The nucleus basalis of Meynert, the major source of cholinergic innervation of the cerebral cortex, was morphometrically investigated in 58 cases of neuropsychiatric disorders and compared to 14 controls. The results demonstrate a loss of neurons in the nucleus basalis of Meynert in Alzheimer's disease (70%), paralysis agitans (77%), and Korsakoff's disease (47%) but no marked reduction of neurons in postencephalitic parkinsonism, Huntington's disease, chronic alcoholism without dementia, schizophrenia and infantile brain damage. Neurons of the three subdivisions of the nucleus basalis of Meynert (the nucleus septi medialis, the nucleus of the diagonal band of Broca and the nucleus basalis Meynert neurons in the substantia innominata) may be affected in a different manner in different patients within a single group homogeneous with respect to the usual clinical and neuropathological diagnostic criteria. Cell loss in the basal forebrain is restricted to the large neurons of the nucleus basalis, the immediately adjacent neurons of the globus pallidus externus not being affected. The selective degeneration of these neurons provides the morphological correlate of the cortical cholinergic deficiency in these neuropathological conditions. The degeneration of this discrete cholinergic neuronal population in several disorders of higher cortical function is probably directly related to the progressive deterioration of memory and cognitive processes in affected patients.

Alcohol Amnestic Disorder↗

[Measurement of radioligand binding to beta-adrenergic and benzodiazepine receptors in the cerebral cortex of the rat. Comparison of filtration and centrifugation technics].

The efficiency of separation of the radioligand receptor complex from the unbound ligand by both rapid filtration and centrifugation is compared for two standard receptor assays in the rat brain: the beta-adrenergic receptor using 3H-dihydroalprenolol and the benzodiazepine receptor using 3H-flunitrazepam. Whereas in beta-adrenergic binding studies both separation procedures yield similar binding data, the apparent binding in the benzodiazepine receptor assay is lower in the filtration experiments as compared to the data obtained by centrifugation, indicating an incomplete retention of the ligand receptor complex by filter. However, in both assays the results of the binding studies are highly dependent on the type of filters used. The following filters were compared: glass fibre filters GE/B and GF/C (Whatman Ltd., Kent, England), membrane filter HAWP (pore size 0.45 micrometer, Millipore Corporation, Bedford, U.S.A.) and glass fibre filters NK I, NK VIII, NK-15-90, NK 13-90, NK 14-120 (all produced by VEB Feinpapierfabrik Neu-Kaliss, G.D.R.). Although a somewhat higher specific binding can be obtained by the membrane filter and several types of the NK filters as compared to the most widely used Whatman GF/C the manifold higher unspecific binding of the radioligand by these filters does not favour their use in ligand assays. Retention as well as unspecific binding of the filter NK VIII is very similar to the Whatman GF/C filter. This new filter seems, therefore, well suited for radioligand studies.

Animals↗

The effect of d-amphetamine and amitriptyline administered to pregnant rats on the locomotor activity and neurotransmitters of the offspring.

d-Amphetamine and amitriptyline (AT) were administered daily to female rats from day 7 of pregnancy until birth of the litters. Changes in the concentration of the biogenic amines, some of their metabolites, GABA, and the activities of glutamate decarboxylase, acetylcholinesterase (AChE), and choline acetyltransferase were determined in the whole brain of the offspring. The offspring of the amphetamine-treated rats showed a marked increase in serotonin concentration and that of its metabolite on postnatal day 1. Changes in the concentration of GABA were apparent on days 15 and 21 and were inversely correlated with changes in the activity of the synthesizing enzyme: Choline acetyltransferase and AChE activities were also increased at this time. Changes in neurotransmitter metabolism were not so evident in the offspring of rats treated with AT. The locomotor activity of the 8-, 15-, and 21-day offspring was also assessed. The offspring of the amphetamine-treated rats showed enhanced locomotor activity initially, but the activity decreased relative to the age-matched controls in the 21-day group. Offspring from the AT-treated group showed reduced locomotor activity.

Amitriptyline↗

Development of muscarinic cholinergic receptor binding in the visual system of monocularly deprived and dark reared rats.

In 25 day old rats monocularly deprived by unilateral eyelid suture on postnatal day 10 (MD), [3H]quinuclidinyl benzylate (3H-QNB) binding was significantly reduced in the visual cortex (VC) of both sides, but elevated in both superior colliculi (SC). Muscarinic receptor binding in the frontal cortex (FC), a non-visual brain area, in the lateral geniculate nucleus (LGN), and in the retina was not affected. In 25 day old rats raised in complete darkness from birth (DR) similar changes in 3H-QNB binding were found in VC and SC. However, binding levels were also decreased in the FC and significantly increased in the retina. In adult (6 month old) MD and DR rats the differences in 3H-QNB binding as compared to age-matched controls had disappeared completely in all visual brain areas studied. Detailed Scatchard analyses indicate that the alterations in the 3H-QNB binding were due to changes in receptor number only.

Aging↗

Cholinergic projections from the basal forebrain to frontal, parietal, temporal, occipital, and cingulate cortices: a combined fluorescent tracer and acetylcholinesterase analysis.

The morphologies, intercellular organization, and cortical projection patterns of putative cholinergic neurons in the basal forebrain of the rat were examined by use of fluorescent tracer histology in combination with the pharmacohistochemical regimen for acetylcholinesterase (AChE). Intensity staining AChE-containing cells projecting to frontal sensorimotor (Area 10), parietal (Area 2), and temporal (Area 4) cortices were found ipsilaterally in nucleus preopticus magnocellularis, in nucleus basalis, and in association with the substantia innominata, the ansa lenticularis, and the lateral hypothalamic area; an essentially rostrocaudal topography was observed for these projections. AChE-containing pathways to cingulate (Area 29) and visual (Area 17) cortices derived from ipsilateral somata associated with the vertical and horizontal limbs of the diagonal band, nucleus preopticus magnocellularis, rostral portions of nucleus basalis, and the substantia innominata. Neurons innervating Area 29 were generally located more rostrally than those giving rise to AChE afferents to Area 17. The vast majority of cells appeared to innervate relatively discrete areas of the cortex. Evidence for collateralization was found only in neurons projecting to visual and cingulate cortices, and these represented only 3.2% of the cells providing AChE afferents to Areas 17 and 29. The basal forebrain AChE projection cells were typically large (greater than 25 micron in maximum cell body extent), and their somata were predominantly oval, with lesser proportions being fusiform or triangular. Many were organized in clusters, particularly in nucleus basalis.

Acetylcholine↗

The effect of visual deprivation on beta-adrenergic receptors in the visual centres of the rat brain.

The levels of binding of [3H]dihydroalprenolol to beta-adrenergic receptors in the visual centres and frontal cortex from brains of control, dark-reared and monocularly deprived rats were compared. Receptor binding is changed in monocularly deprived rats in the lateral geniculate nuclei and superior colliculi of both sides. Scatchard analyses indicated that the changes in the [3H]dihydroalprenolol binding in the lateral geniculate nuclei were due to alterations in both receptor affinity and receptor number. No effect of dark-rearing could be detected.

Aging↗

Effect of magnocellular forebrain nuclei lesions on acetylcholine output from the cerebral cortex, electrocorticogram and behaviour.

ACh output from the cerebral cortex, electrocortical activity, spontaneous alternation and the acquisition of a conditioned avoidance response have been investigated in rats 20 days after the placement of a unilateral lesion of the magnocellular forebrain nuclei (MFN). ACh output from the hemisphere ipsilateral to the lesion was 40% lower than in sham operated rats. Electrocortical activity quantified with a frequency analyzer supplemented by a period and power spectrum analysis showed a marked asymmetry between the two hemispheres of the lesioned rats. The total electrical activity was strongly reduced over the lesioned hemisphere. The reduction involved all frequencies but was more evident in the high frequencies. In the lesioned rats spontaneous alternation was not impaired and spontaneous motility was enhanced while the acquisition of a conditioned active avoidance in a two-way shuttle box was significantly hampered. The possibility is envisaged that the destruction of cholinergic fibres impinging upon the cerebral cortex may decrease cortical activation and impair the selective awareness necessary for information acquisition and exclusion of irrelevant output.

Acetylcholine↗

[Cholinergic mechanisms in the retina of rats].

In rats with extra- or intracranial dissection of the visual pathway the activities of acetylcholinesterase (AChE) and choline acetyltransferase (ChAc) were determined in retina, optic nerve and optic tract quantitatively by bio- and histochemical methods after one or five weeks of survival time. One week after intracranial (chiasma-near) dissection of the optic nerve an initial ipsilateral enhancement in the enzyme activity of AChE was found histochemically in retina layers and optic nerve. Five weeks following the dissection significant losses in AChE activity could be determined in the optic nerve, less pronounced in the retina. However, the activity of ChAc in the retina never was changed, neither after short nor after long survival times. Therefore, the high activity of both enzymes connected with cholinergic transmission normally present in different retinal layers must belong to local neurons, probably amacrine cells. To elucidate the question of the existence of a centrifugal cholinergic innervation of the retina one eye was enucleated. One week after operation a significant increase in the activity of AChE and ChAc was found in central parts of the dissected optic nerve and in the opposite optic tract indicating the existence of centrifugal cholinergic fibers in the optic nerve, but no evidence for the origin of these fibres could be obtained. The possible role of a central cholinergic control of the visual information processing already in retinal level is discussed in analogy to similar results obtained in the olfactory bulb.

Acetylcholinesterase↗

Cholinergic projections from magnocellular nuclei of the basal forebrain to cortical areas in rats.

Acetylcholinesterase (AChE) and choline acetyltransferase (CHAc) activities were studied by quantitative histochemical (AChE) as well as biochemical methods (AChE, ChAc) in certain cortical brain areas in rats after stereotaxic lesions had been placed in several structures of the basal forebrain. After lesioning the magnocellular nuclei of the substantia innominata (nuc. basalis Meynert, NBM) the activities of AChE and ChAc decreased to moderate or low residual values in the ipsilateral cortical areas. This indicated that cholinergic pathways were directly linked to frontal, sensory-motor, auditory and visual cortex. After lesions of the globus pallidus the decrease in cortical AChE activity was less pronounced. Lesions of the caudate, accumbens or entopeduncular nucleus did not influence the cortical AChE activities. The results are discussed with respect to the similarity of the organization of the cholinergic projection to the cortex arising from NBM cells and the monoaminergic system which innervates the cortex. It is suggested that both neurotransmitter systems by their interaction might modulate and control cortical information processing and behavior in a manner analogous to the control of peripheral activity by the sympathetic and parasympathetic system.

Acetylcholinesterase↗

Cholinergic transmission in subcortical and cortical visual centers of rats: no evidence for the involvement of primary optic system.

The effect of unilateral enucleation, ablation of the visual cortex or coagulation of the lateral geniculate nucleus (LGN) upon the activity of choline acetyltransferase (ChAc) and acetylcholinesterase (AChE) in different structures of the visual system of albino rats was studied. The localization and extent of the degeneration pattern were followed up by histological silver degeneration methods. Afferents from the retina project mainly contralaterally to the dorsal and ventral LGN, the pretectal region and the superior colliculus. Afferent fibres from the dorsal LGN enter the visual cortex in area 17 only. Neurons of this area project back ipsilaterally to the LGN and the superior colliculus (SC). No significant decrease in the activity of the cholinergic marker enzyme choline acetyltransferase could be observed under any of the experimental conditions; there was rather a tendency to increased activity in the subcortical centres. AChE as a less specific marker also exhibited no gross changes in activity in the lesioned animals. The results add more direct proof to pharmacological and physiological evidence that ACh is not involved in the synaptic transmission of the direct optic projections in rats, either at the subcortical or at the cortical level.

Acetylcholinesterase↗