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A Rotter

Publications and source records attributed to A Rotter.

At least 37 records · Page 2Linked to original sources
PubMed1993

GABAA/benzodiazepine receptor gamma 2 subunit gene expression in developing normal and mutant mouse cerebellum.

Recent studies have identified several subunits (alpha, beta, gamma and delta) of the gamma-aminobutyric acidA/benzodiazepine receptor; each consists of several variants. The gamma 2 subunit appears to mediate the interaction of the alpha and beta subunits making the receptor capable of modulation by benzodiazepines. In the present studies, the expression of mRNA encoding the gamma 2 subunit was examined in the cerebellum during development and in adult Purkinje cell degeneration, lurcher and reeler mutant mice. In the normal adult cerebellum, in situ hybridization with [35S]cRNA probes revealed a strong signal over the Purkinje cell layer and deep cerebellar nuclei, and a weaker signal over basket, stellate and granule cells. Labeling over Purkinje cells was detectable at birth, gradually becoming stronger and more punctate during postnatal weeks 1 and 2, as Purkinje cells formed a monolayer between the molecular and granule cell layers. Adult levels of grain density were reached by P20. The external germinal layer, which contained proliferating granule cells, was unlabeled throughout development; however, weak labeling was detected over the internal granular layer at the end of postnatal week 1, as granule cells began their migration across the molecular layer. During the second postnatal week, punctate labeling became visible over the molecular layer in a distribution indicative of basket and stellate cells. In adult Purkinje cell degeneration and lurcher mutants, in which Purkinje cells have degenerated, no punctate labeling characteristic of mature Purkinje cells was detected. In adult and developing reeler mutants, where all classes of cells are malpositioned throughout the cerebellum, the punctate hybridization signal was present and clearly associated with Purkinje cells in all cortical regions. Our results suggest that developing Purkinje cells express the gamma 2 gene at a time prior to receiving GABAergic inhibitory input, and that the continued expression in the adult is not affected by the absence of afferents.

Adult↗
PubMed1993

[Effect of enalapril and terazosin on lipid metabolism in patients with essential arterial hypertension and accompanying hypercholesterolemia].

The effect of enalapril and terazosin on serum lipid profile was investigated in 36 patients with primary hypertension and hypercholesterolemia (total cholesterol 5.2 mmol l). 6- and 12-week monotherapy with these drugs did not produce any unfavourable changes in: total cholesterol, LDL- and HDL-cholesterol, triglycerides, apolipoproteins A1 and B as well as in serum lipids. Enalapril and terazosin seem to be very useful as a first step monotherapy especially in patients with hypertension and lipid disturbances.

Adrenergic alpha-Antagonists↗
PubMed1992

Differential expression of GABAA/benzodiazepine receptor beta 1, beta 2, and beta 3 subunit mRNAs in the developing mouse cerebellum.

Gamma aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian cerebellum. Cerebellar granule, Purkinje, and deep nuclear neurons are known to receive GABAergic afferents. Since GABA exerts its inhibitory effects via GABA receptors, it is of interest to determine the temporal relationship between the formation of GABAergic synapses and the expression of genes coding for the GABA receptor. In a previous study, we have examined the developmental expression of binding sites for [3H]muscimol, which binds with high affinity to the beta subunits of the GABAA/benzodiazepine (GABAA/BZ) receptor. In the present study, [35S]cRNA probes were used to examine the appearance and distribution of GABAA/BZ beta 1, beta 2, and beta 3 subunit mRNAs in the developing C57BL/6 mouse cerebellum by in situ hybridization. In the adult cerebellum, the distribution of the three subunit mRNAs was clearly different, despite considerable overlap, and their temporal expression differed throughout postnatal development. The beta 1 hybridization signal appeared within the cerebellar cortex during the second postnatal week as a discrete band at the interface of the molecular and granule cell layers. Grains were distributed diffusely over small densely staining cells surrounding the Purkinje cells; relatively few grains were visible over Purkinje cell bodies themselves. This distribution may reflect an association with Bergmann glia or basket cells. The beta 2 and beta 3 hybridization signals were present considerably earlier than that of the beta 1 mRNA. The beta 2 signal was present at birth in the molecular/Purkinje cell layer; as development progressed, the signal became increasingly intense over both granule and Purkinje cells. At birth, the beta 3 subunit mRNA was present in the external germinal and molecular layers, later becoming largely localized within the granule cell layer. Dense beta 2 and beta 3 cRNA probe labeling was present over the adult granule cell layer. Moderate levels of beta 2 signal were seen over Purkinje cell bodies; considerably less labeling was observed with the beta 3 probe. The adult distribution of beta 2 and beta 3 cRNA probes showed good spatial correspondence with the known GABAA receptor beta subunit markers, [3H]-muscimol and the mAb 62-3G1 antibody, each being present within the granule cell layer. Our results indicate that the temporal expression of GABAA/BZ receptor beta subunit messages within a given cell type may be independently regulated, and that acquisition of the beta 2 and beta 3 mRNAs occurs before these cells become integrated into mature synaptic circuits.

Animals↗
PubMed1992

Ontogeny of GABAA/benzodiazepine receptor subunit mRNAs in the murine inferior olive: transient appearance of beta 3 subunit mRNA and [3H]muscimol binding sites.

The GABAA/benzodiazepine receptor consists of at least four subunits, alpha, beta, gamma and delta, each comprised of several variants. The developmental expression of the alpha 1, beta 1-3, gamma 2 and delta subunits was studied in the murine inferior olivary nucleus by in situ hybridization with antisense cRNA probes. The postnatal appearance and distribution of [3H]flunitrazepam and [3H]muscimol binding sites, alpha and beta subunit-specific ligands respectively, were also studied autoradiographically. The beta 3 subunit was transiently expressed in each of the subnuclei of the inferior olive: The signal was strong at birth, increased throughout postnatal week 1 and rapidly declined thereafter to low adult levels. A similar pattern of labeling was observed with [3H]muscimol. Detectable levels of alpha 1 subunit mRNA hybridization signal and [3H]flunitrazepam binding sites were also present in the inferior olive at birth, decreasing thereafter. Low to moderate levels of beta 1, beta 2, and gamma 2 subunit mRNAs were present in olivary neurons throughout postnatal development, while delta mRNAs were largely absent. It has been reported previously that, during the 2nd postnatal week, the ratio of climbing fiber terminals to Purkinje cells is reduced from 3:1, as observed in neonates, to the 1:1 relationship observed in the adult cerebellar cortex. Our results raise the possibility that the subunit composition of the GABAA/benzodiazepine receptor in inferior olivary neurons undergoes changes during development, and that this process may be related to the elimination of multiple climbing fiber innervation of cerebellar Purkinje cells.

Animals↗
PubMed1991

Stability of GABAA/benzodiazepine receptor alpha 1 subunit mRNA expression in reeler mouse cerebellar Purkinje cells during postnatal development.

A [35S]cRNA probe was used for the visualization of GABAA/benzodiazepine (GABAA/BZ) receptor alpha 1 subunit mRNA in developing reeler mutant mouse cerebellum. A clear hybridization signal was observed throughout the malformed reeler cerebellum from birth. Labeling was associated with Purkinje cell bodies located in three subcortical masses. Additional labeled Purkinje cells were observed within the granule cell layer and at their normal position at the interface between the molecular and granule cell layers. All reeler Purkinje cells had comparable levels of grain density, regardless of their location within the cerebellar cortex. These results indicate that Purkinje cell malpositioning, and the resulting absence of a major complement of afferents throughout development, does not impair the expression of mRNA coding for the alpha 1 subunit of the GABAA/BZ receptor.

Animals↗
PubMed1991

Expression of GABAA/benzodiazepine receptor alpha 1-subunit mRNA and [3H]flunitrazepam binding sites during postnatal development of the mouse cerebellum.

Previous studies have shown that the alpha subunit of the GABAA receptor contains the flunitrazepam binding site. In the present study, in situ hybridization and receptor autoradiography were used to examine the temporal and spatial relationships between alpha 1 subunit mRNA and [3H]flunitrazepam binding sites in the developing mouse cerebellum. A [35S]cRNA probe was used to study the expression of GABAA/benzodiazepine receptor alpha 1 subunit mRNA by in situ hybridization. At postnatal day (P) 1, a diffuse band of labeling was observed in the molecular/Purkinje cell layer; subsequently, this band became progressively more concentrated and restricted to the interface between the granular and molecular layers. By P5-P7, high intensity labeling was clearly associated with Purkinje cells. Clusters of grains became visible over basket and stellate cells in the molecular layer between P11 and P13; the internal granule cell layer and the deep cerebellar nuclei showed an increasingly strong hybridization signal during postnatal development. The external germinal layer was devoid of labeling throughout its existence. The developmental distribution of [3H]flunitrazepam binding sites was studied by receptor autoradiography. Cerebellar labeling was detectable at birth, with the highest levels present over the deep cerebellar nuclei, and relatively low levels equally distributed over the molecular and Purkinje cell layers. Cerebellar cortical grain density increased gradually during postnatal weeks 1 and 2, with the molecular, Purkinje and granule cell layers remaining essentially equally labeled. Between P11 and P15, the labeling over the molecular layer increased dramatically, reaching the high adult levels by P20. As with the in situ hybridization studies, there was a complete absence of [3H]flunitrazepam binding sites in the external germinal layer throughout development. These results indicate that, in the Purkinje cell, the production of mRNA and the synthesis of the alpha 1 subunit occur prior to the formation of afferent inhibitory synapses, suggesting that GABAA/benzodiazepine receptor expression precedes, and is independent of GABAergic synaptic input.

Aging↗
PubMed1991

Distribution of muscarinic receptors in the developing rodent cerebellum.

The distribution of muscarinic receptors in the developing rodent cerebellum was studied by light microscopic autoradiography of [3H]quinuclidinyl benzilate binding sites. Muscarinic receptors were not detected in the mouse cerebellar plate until embryonic day 16, at which time they were clustered in the ventromedial region of the cerebellar anlagen. At postnatal day 1, additional areas of higher grain density became visible in the dorsolateral medullary zone, internal to the newly forming granular layer. Labeling increased throughout the entire cerebellum between postnatal days 5 and 10, becoming markedly higher in the lateral hemispheres than in the vermis. This elevated density of binding sites in the hemispheres became reduced to that of the vermis by postnatal day 13 in the mouse, and PD20 in the rat. In adult animals, the cortical grain density was highest in the granule and Purkinje cell layers, low in the molecular layer and absent from the white matter. Receptor labeling was, however, observed over many areas of white matter throughout early development; this became more restricted to specific tracts during the third postnatal week. At no time during development were binding sites observed in the external germinal layer. Microvessels and capillaries, structures which have been shown to contain [3H]quinuclidinyl benzilate binding sites, may partially account for the observed ontogenic pattern.

Aging↗
PubMed1988

Topographical distribution of muscarinic cholinergic receptors in the cerebellar cortex of the mouse, rat, guinea pig, and rabbit: a species comparison.

Light microscopic autoradiography of [3H]quinuclidinyl benzilate (QNB) binding sites was used to study the distribution of muscarinic acetylcholine receptors in the mouse, rat, guinea pig, and rabbit cerebellar cortex. In the mouse, the laminar distribution of grain density was similar throughout the cortex, with slightly higher levels over lobules IX and X. The highest [3H]QNB labeling was present over the granule cell layer, and low levels were observed over the molecular layer. In the rat, the general distribution was similar to that of the mouse in that the granule cell layer was most densely labeled and the highest concentration of [3H]QNB binding sites was present in lobules IX and X of the archicerebellum. In these lobules, however, the laminar distribution of grain density was reversed so that the molecular layer was more densely labeled than the granule cell layer. In addition, several discrete columns of elevated grain density traversed the granule cell layer in caudal regions of lobule IX. The distribution of [3H]QNB binding sites in the guinea pig cerebellum was similar to that of the rat in that the molecular layer of lobules IX and X was again more intensely labeled than other cerebellar regions. In the remaining lobules, grain density was equal over the granule cell and molecular layers. In the rabbit cerebellar cortex, slightly higher grain density was observed in the granule cell layer than in the molecular layer. In lobules IX and X and in the hemisphere of X, the Purkinje cell layer was most densely labeled; parasagittal columns of very high grain density were present over the molecular layer of several cortical regions, including lobules, I, II, III, IV, V, IX, X, and the hemispheres of IX and X. Since muscarinic receptors have previously been found on blood vessels, there is a possibility that some proportion of receptor labeling may be localized to these structures. Microvessels and capillaries in each of the species examined were more numerous in the granule cell layer than in the molecular layer and white matter. The distribution of blood vessels in many cerebellar lobules of mice, rats, and guinea pigs corresponded quite closely to the general distribution of [3H]QNB binding sites. Unique patterns of labeling in lobules IX and X were not accompanied by corresponding patterns of blood vessel distribution, however. In the mouse, there was a slight increase in muscarinic receptor density observed in the archicerebellum, with no corresponding increase in the density of blood vessels.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Cerebellar benzodiazepine receptors: cellular localization and consequences of neurological mutations in mice.

The distribution of cerebellar [3H]flunitrazepam binding sites was studied autoradiographically in Purkinje cell degeneration (pcd/pcd), weaver (wv/wv), staggerer (sg/sg) and reeler (rl/rl) mutant mice. In the normal 78-day-old C57BL/6J mouse cerebellum, the highest concentration of [3H]flunitrazepam binding sites was observed over the molecular layer. Intermediate grain density was present over the Purkinje cell layer and intermediate to high density over the deep cerebellar nuclei. Low labeling was observed over the granule cell layer. Negligible concentrations of binding sites were seen in the white matter. In 45-49-day-old Purkinje cell degeneration mutants, where essentially all Purkinje cells have disappeared by day 45, there was a small decrease in grain density over the cerebellar cortex. Concomitantly, a substantial increase in grain density was observed over the deep cerebellar nuclei of the pcd/pcd mutants when compared to littermate controls. A significant increase in [3H]flunitrazepam labeling was observed over the cerebellar cortex of 81-86-day-old wv/wv mutants; this was most pronounced in the vermis where the granule cell loss was greatest. Over the hemispheres, where fewer granule cells degenerate, a lower density of binding sites was seen. Grain density over the wv/wv deep cerebellar nuclei was comparable to that of littermates. Substantially lower [3H]flunitrazepam labeling was detected over the cerebellar cortex of 25-27-day-old sg/sg mutants in which the number of granule, Purkinje and Golgi cells is greatly reduced; the labeling over the deep nuclei, however, was significantly increased. In 27-29-day-old rl/rl mutant cerebella, where all classes of cells are malpositioned, labeling density over all areas of the cerebellar cortex, including the Purkinje cell masses, was increased. Our autoradiographic data suggest that a proportion of cerebellar cortical benzodiazepine receptors are associated with Purkinje cells; we propose that the remainder of the receptors are localized on Golgi cells, while granule cells are devoid of receptors. In the deep cerebellar nuclei, the observed increase in benzodiazepine receptors in the pcd/pcd and sg/sg mutants may be a manifestation of denervation supersensitivity subsequent to the loss of innervation by Purkinje cell axon terminals. The finding of a high receptor density in the Purkinje cell masses of the rl/rl mutant, where Purkinje cells are devoid of afferent basket cell input, suggests that benzodiazepine receptors are expressed and maintained in the absence of a full complement of GABAergic afferents.

Animals↗
PubMed1988

The localization of GABAA receptors in mice with mutations affecting the structure and connectivity of the cerebellum.

The distribution of cerebellar [3H]muscimol binding sites was studied autoradiographically in normal C57BL/6J mice and in the weaver, reeler, Purkinje cell degeneration and staggerer mutant mice. In the normal 79-day-old mouse cerebellum, the highest concentration of [3H]muscimol binding sites was observed in the granule cell layer. A much lower grain density was present over the Purkinje cell and molecular layers and negligible numbers of binding sites were seen over the deep cerebellar nuclei and white matter. A significant decrease in [3H]muscimol labeling was observed over the cerebellar cortex of the 81-86-day-old weaver mutant; this was most pronounced in the vermis where granule cell loss was the greatest. Over the hemispheres, where fewer granule cells degenerate, a higher density of binding sites remained. In the 27-29-old reeler cerebellum, where Purkinje cells are malpositioned, no labeling was seen over the deep Purkinje cell masses. In the quasi-normal superficial cortex, labeling density over the surviving granule cell layer was only slightly decreased. In the 54-57-day-old Purkinje cell degeneration mutant, where essentially all Purkinje cells have disappeared by day 45, a 29% decrease in grain density over the granule cell layer was observed, while labeling was still present in the molecular layer. Virtually no [3H]muscimol labeling was detected over any part of the cerebellar cortex of the 25-27-day-old staggerer mutant (which lacks parallel fiber-Purkinje cell synapses), although clusters of surviving granule cells were present in significant numbers in the lateral aspects of the cortex. Our autoradiographic data indicate that GABAA receptors are associated with granule cells in both the molecular and granule cell layers. Furthermore, our results raise the possibility that the maintenance of receptor levels may be dependent upon synaptic contacts between the granule cell and its main postsynaptic target, the Purkinje cell.

Animals↗
PubMed1988

On the cellular localization of cerebellar muscarinic receptors: an autoradiographic analysis of weaver, reeler, Purkinje cell degeneration and staggerer mice.

Light microscopic autoradiography of [3H]quinuclidinyl benzilate binding sites was used to study the distribution of muscarinic cholinergic receptors in mouse mutants which have abnormalities affecting specific cerebellar cell types. In the normal C57BL/6J mouse, binding sites were distributed throughout the cerebellar cortex, with the highest levels in the granule cell layer and deep cerebellar nuclei. Normal binding site density was observed in the cerebellum of the weaver mutant in which the majority of granule cells had degenerated. The density of [3H]quinuclidinyl benzilate binding sites was elevated in the cortex of the reeler, despite a reduction in the number of granule cells. The concentration of binding sites was also high over the Purkinje cell masses where granule cells were largely absent. No significant reduction in cortical [3H]quinuclidinyl benzilate binding site density was detected in the Purkinje cell degeneration mutant, in which essentially all Purkinje cells had degenerated. In contrast, receptor binding in the deep cerebellar nuclei of this mutant was significantly increased. A substantial increase in labeling was observed in the cortex and deep nuclei of the staggerer cerebellum in which a large fraction of Golgi II cells, Purkinje cells, granule cells and mossy fibers have degenerated. We discuss the possibility that the persistence of [3H]quinuclidinyl benzilate binding sites in all four mutants may imply a non-neuronal localization for a large proportion of muscarinic receptors in the mouse cerebellar cortex.

Animals↗
PubMed1987

The ontogeny of [3H]muscimol binding sites in the C57BL/6J mouse cerebellum.

The characteristics of [3H]muscimol binding were investigated in cerebellar sections from 7-day-old mice. The binding sites were found to possess the kinetic properties and pharmacological specificity characteristic of high-affinity GABAA receptors. [3H]Muscimol binding sites in the developing C57BL/6J mouse cerebellum were visualized by light microscopic autoradiography. A distinct band of labeling situated over the molecular layer was apparent from day 1 to day 7. The external granule cell layer remained unlabeled throughout development. Labeling over the internal granule cell layer gradually increased from birth; it became more dense and well defined until adult levels of grain density were reached at 35-42 days of age. The deep cerebellar nuclei were moderately labeled at birth and gradually decreased in density thereafter. The observed ontogeny of granule cell [3H]muscimol binding sites suggests that the synthesis of receptors is initiated at a time immediately after cessation of cell division, coinciding with the beginning of granule cell translocation across the molecular layer. Since, at this time, granule cells have not yet formed synapses with the GABAergic Golgi II cells, nor have they, in turn, formed the vast majority of synaptic contacts with Purkinje cells, it follows that receptor appearance precedes the formation of afferent connections, and may also precede efferent synaptic contacts. The timing of the appearance of [3H]muscimol binding sites raises the possibility that their initial acquisition may be related to developmental events other than the interaction of the granule cell with its pre- or postsynaptic neuronal partners.

Animals↗
PubMed1987

Neuronal localization of pseudocholinesterase in the rat cerebellum: sagittal bands of Purkinje cells in the nodulus and uvula.

The histochemical distribution of pseudocholinesterase was studied in the rat cerebellum using Koelle's copper-thiocholine method. Throughout the cerebellum, pseudocholinesterase is uniformly localized in the endothelial cells of blood vessels and in the cell bodies and processes of the Bergmann glia. In addition, we demonstrate that exclusively in the ventral uvula and in the nodulus (lobules IXc and X of Larsell) pseudocholinesterase is localized in a small subpopulation of Purkinje cells. The cell bodies and dendrites of these labeled Purkinje cells form at least 4 distinct parallel bands extending along the sagittal plane of each of the lobules. Two broad bands on either side of the midline, approximately 800-900 microns wide and composed of 15-20 Purkinje cells have been designated as A bands. Two narrower bands, approximately 160-300 microns wide and composed of 5-7 Purkinje cells, on the lateral aspects of the lobules have been designated as B bands. The unique distribution of pseudocholinesterase in a small and anatomically restricted population of neurons suggests that in the cerebellum this enzyme may play a role in the metabolism of neuroactive substances.

Animals↗
PubMed1987

No mood-altering effects found after treatment of normal subjects with bright light in the morning.

Studies have shown that depressed patients with seasonal affective disorder (SAD) respond to treatment with bright artificial light. In this study 2 hours of bright artificial light administered in the morning for 1 week did not alter mood in 11 normal subjects. This finding suggests that the mood-enhancing effect of light for SAD patients is not necessarily generalizable to other populations.

Affect↗
PubMed1986

Cerebellar benzodiazepine receptor distribution: an autoradiographic study of the normal C57BL/6J and Purkinje cell degeneration mutant mouse.

The distribution of [3H]flunitrazepam binding sites in the cerebella of normal mice and Purkinje cell degeneration mutant mice was studied by light microscopic autoradiography. In the cerebellar cortex of normal mice, a high density of [3H]flunitrazepam binding was observed over the molecular layer, an intermediate density over the Purkinje cell layer and a low density over the granule cell layer; the white matter was devoid of labeling. The deep cerebellar nuclei were labeled to an intermediate density. In the 54-day-old Purkinje cell degeneration mutant cerebellum, which is depleted of Purkinje cells, a 36% reduction in labeling density of the cerebellar cortex was observed. The density was reduced by approximately equal amounts in both the molecular and granule cell layers; labeling in the deep cerebellar nuclei was, however, substantially increased.

Animals↗
PubMed1986

Autoradiographic localization of receptors in the cochlear nucleus of the mouse.

Light microscopic autoradiography of bound radiolabeled ligands was used to describe the distribution of six receptor types in the dorsal and ventral mouse cochlear nuclei: Glycine receptor ([3H]strychnine); GABA receptor ([3H]muscimol); benzodiazepine receptor ([3H]flunitrazepam); adenosine receptor ([3H]cyclohexyladenosine); muscarinic ACh receptor ([3H]quinuclidinyl benzilate); histamine receptor ([3H]mepyramine). The most intense [3H]strychnine labeling was observed in the deep region of the dorsal cochlear nucleus (DCN), with slightly lower levels in the molecular and pyramidal layers. Highest density of [3H]muscimol binding sites was observed in the granule cell layer of the posterior ventral nucleus (PVCN) and in the pyramidal layer of the DCN. Diffuse [3H]flunitrazepam labeling was distributed over all laminar regions of the DCN; the highest grain density was observed over the granule cell layer of the PVCN. Intense [3H]cyclohexyladenosine labeling was seen over the molecular layer, possibly extending into the pyramidal layer, of the DCN. The granule cell layer of the PVCN was also densely labeled. High concentrations of [3H]quinuclidinyl benzilate sites were seen in the molecular layer, possibly extending into the pyramidal layer, of the DCN. A thin band of high grain density was also visible over the granule cell layer of the PVCN. Moderate, diffuse [3H]mepyramine labeling was visible throughout the DCN, with slightly higher grain density over the molecular, and possibly the pyramidal layers, than over the deep region of the DCN.

Animals↗