Thyrotropin nyctohemeral pattern in primary depression : Differences between unipolar and bipolar women

The nyctohemeral patterns of serum thyrotropin (TSH) levels were studied in thirteen female patients suffering from primary affective illness (5 bipolars and 8 unipolars); they were compared to the nyctohemeral profiles obtained in six normal female subjects. The periodogram analysis showed striking differences in TSH circadian rhythms between unipolar and bipolar patients. The nyctohemeral TSH patterns in bipolar patients were similar to those obtained in controls. Unipolar patients, compared to controls, had a significantly lower 24-hour TSH mean, a lower sleep-wake ratio of TSH and an absence of nocturnal rise of TSH. The alterations of the circadian rhythm of TSH secretion observed in the depressive phase of unipolar illness may be a relevant neuroendocrine indicator of hypothalamic-pituitary dysfunction in primary depressive illness.     

I. The 24-hour profile of prolactin in depression

The 24-hour profile of plasma PRL was studied in 10 patients with unipolar depression and 8 patients with bipolar depression and compared to 18 control profiles obtained in healthy subjects. Alterations in the basal PRL secretion as well as the characteristics of the 24-hour rhythm were found in all patients but differed strikingly according to the type of depressive illness. The basal PRL level was elevated in unipolars, mainly as a result of increased secretion during wakefulness, and lowered in bipolars because of a lack or reduction of sleep-associated elevation. The nocturnal rise of PRL was maintained in unipolars but absent in 75% of the bipolar subjects. The variability of PRL levels around the 24-hour mean appeared to be reduced in both types of affective illness. These abnormalities in the 24-hour profile of PRL could serve as a biological marker of sub-types of depression.     

Ultrathin structure of the main lateral nerve cords and accompanying elements of Triaenophorus nodulosus (Cestoda: Pseudophyllidea)

The ultrastructure of lateral nerve cords (LNC) of Triaenophorus nodulosus has been studied. 4 of the 6 types of neurones earlier reported for cerebral ganglia are present in LNC: multipolars, bipolars, unipolars and "light"; neurosecretory cells of the 7th type lie in transverse commissures. The growth and formation of LNC occur at the expense of undifferentiated cells found on the cord periphery among mature neurones. LNC are surrounded with specialized envelopes made of cell processes of excretory vessels and a fibrillar matrix formed at early stages of cestode development. In large axons, cisternae of the cross reticulum are detected, which can serve as ultrastructural marker of the synapse. Two types of muscle innervation are determined. The direct innervation of muscular fibres is realized by peripheral neurosecretory neurones, which form contacts of the paracrine type. The central or sarco-neural innervation of muscular fibers occurs in LNC via the entering muscular processes.     

Affected-sib-pair analyses reveal support of prior evidence for a susceptibility locus for bipolar disorder, on 21q.

In 22 multiplex pedigrees screened for linkage to bipolar disorder, by use of 18 markers on chromosome 21q, single-locus affected-sib-pair (ASP) analysis detected a high proportion (57%-62%) of alleles shared identical by descent (IBD), with P values of .049-.0008 on nine marker loci. Multilocus ASP analyses revealed locus trios in the distal region between D21S270 and D21S171, with excess allele sharing (nominal P values <.01) under two affection-status models, ASM I (bipolars and schizoaffectives) and ASM II (ASM I plus recurrent unipolars). In addition, under ASM I, the proximal interval spanned by D21S1436 and D21S65 showed locus trios with excess allele sharing (nominal P values of .03-.0003). These findings support prior evidence that a susceptibility locus for bipolar disorder is on 21q.     

The distribution of nerve cells inHydra attenuata Pall.

Summary Polyps ofHydra attenuata Pall. were subdivided into four axial fragments (I–IV) of about identical length. Ecto- and endoderm of each of these fragments were separated from each other and dissociated according to the technique of David (1973). Each preparation was qualitatively and quantitatively examined as to its content of nerve cells.The presence of 11 different types of nerve cells (Tardent and Weber, 1976) could be confirmed. While multipolars (M₁, M₂), symmetrical bipolars (B₁, B₂) and unipolars (U₁, U₂) were found in both layers, asymmetrical bipolars (B_3–7) are limited to the endoderm (Fig. 1), which, as a whole, contains fewer nervous elements than the ectoderm (Fig. 2). The ecto- and endoderm of the tentacles could not be separated from each other and the dissociation was only partly successful. It was, however, possible to ascertain that among the nerve cells present in the tentacles the most numerous are the symmetrical bipolars (B₁, B₂).Dr. Epp was awarded a grant of the Swiss National Science Foundation (Nr. 880.480.76). This work was also supported by grant Nr. 3.548.75 of the same Foundation. The authors are indebted to Mr. Chr. Weber for his technical help and advice     

Nonlinear signal transfer from mouse rods to bipolar cells and implications for visual sensitivity

We investigated the impact of rod-bipolar signal transfer on visual sensitivity. Two observations indicate that rod-rod bipolar signal transfer is nonlinear. First, responses of rods increased linearly with flash strength, while those of rod bipolars increased supralinearly. Second, fluctuations in the responses of rod bipolars were larger than expected from linear summation of the rod inputs. Rod-OFF bipolar signal transfer did not share this strong nonlinearity. Surprisingly, nonlinear rod-rod bipolar signal transfer eliminated many of the rod's single-photon responses. The impact on sensitivity, however, was more than compensated for by rejection of noise from rods that did not absorb photons. As a consequence, rod bipolars provide a near-optimal readout of rod signals at light levels near visual threshold.     

Changes in the relative number of bipolar-like cells in the retina of Pleurodeles waltl as a function of age and as a result of light exposure

The study of the population of bipolar-like cells (displaced bipolars) was continued in order to establish their role in development and regeneration of the retina in lower vertebrates. The size of the population of these cells was estimated on serial semithin sections in the retina of normal eyes in adult and young newt Pleurodeles waltl, as well as in adult newts subjected to long-term bright illumination. The population of displaced bipolars was significantly increased with reference to all cells of the outer nuclear layer. In young and illuminated animals, their numbers were approximately 1.3 and 1.4 times that in the adult animals not exposed to constant light. The results obtained favor the earlier suggestion of the involvement of the displaced bipolars in growth and restoration of the outer nuclear layer in the retina of newts during development and after trauma.     

Changes in the Relative Number of Bipolar-Like Cells in the Retina of Pleurodeles waltl as a Function of Age and as a Result of Light Exposure

The study of the population of bipolar-like cells (displaced bipolars) was continued in order to establish their role in development and regeneration of the retina in lower vertebrates. The size of the population of these cells was estimated on serial semithin sections in the retina of normal eyes in adult and young newt Pleurodeles waltl, as well as in adult newts subjected to long-term bright illumination. The population of displaced bipolars was significantly increased with reference to all cells of the outer nuclear layer. In young and illuminated animals, their numbers were approximately 1.3 and 1.4 times that in the adult animals not exposed to constant light. The results obtained favor the earlier suggestion of the involvement of the displaced bipolars in growth and restoration of the outer nuclear layer in the retina of newts during development and after trauma.     

Neurons of the human basal ganglia (striatum and basolateral amygdala) expressing the enzyme NADPH-d

In human striatum and basolateral amygdala NADPH-d+ neurons were revealed (after Vincent et al., 1983); and in striatum strio-cortical neurons were also revealed using DiI marker (after Dahtstrom and Belichenko, 1995). The NADPH-d+ neurons were numerous in both formations. Staining of NADPH-d+ neurons with their processes, and our previous study of striatal and amygdalar human neurons by Golgi method made it possible to identify the species of neurons with their assessment as sparsely or densely branched. The main efferent neurons of striatum and basolateral amygdala (densely branched medium spiny and bushy spiny, respectively) and their densely branched interneurons were not marked. Efferent NADPH-d+ neurons included the most numerous ones in both formations. A projection of reticular striatal neurons to cortex was also shown. The NADPH-d+ interneurons belonged to sparsely branched forms. In striatum they included slender-dendritic and long-dendritic bipolars (numerous), ordinary bipolars, twisted and large poor-dendritic cells; in amygdala--the same bipolars and radial cells. Thus, the NADPH-d positive cells in the formations under study were represented by more "ancient" or less structurally complex cell forms.     

The Phosphoinositide Signal Transduction System Is Impaired in Bipolar Affective Disorder Brain

Abstract: The function of the phosphoinositide second messenger system was assessed in occipital, temporal, and frontal cortex obtained postmortem from subjects with bipolar affective disorder and matched controls by measuring the hydrolysis of [³H]phosphatidylinositol ([³H]PI) incubated with membrane preparations and several different stimulatory agents. Phospholipase C activity, measured in the presence of 0.1 mM Ca²⁺ to stimulate the enzyme, was not different in bipolar and control samples. G proteins coupled to phospholipase C were concentration-dependently activated by guanosine 5′-O-(3-thiotriphosphate) (GTPγS) and by NaF. GTPγS-stimulated [³H]PI hydrolysis was markedly lower (50%) at all tested concentrations (0.3–10 µM GTPγS) in occipital cortical membranes from bipolar compared with control subjects. Responses to GTPγS in temporal and frontal cortical membranes were similar in bipolars and controls, as were responses to NaF in all three regions. Brain lithium concentrations correlated directly with GTPγS-stimulated [³H]PI hydrolysis in bipolar occipital, but not temporal or frontal, cortex. Carbachol, histamine, trans-1-aminocyclopentyl-1,3-dicarboxylic acid, serotonin, and ATP each activated [³H]PI hydrolysis above that obtained with GTPγS alone, and these responses were similar in bipolars and controls except for deficits in the responses to carbachol and serotonin in the occipital cortex, which were equivalent to the deficit detected with GTPγS alone. Thus, among the three cortical regions examined there was a selective impairment in G protein-stimulated [³H]PI hydrolysis in occipital cortical membranes from bipolar compared with control subjects. These results directly demonstrate decreased activity of the phosphoinositide signal transduction system in specific brain regions in bipolar affective disorder.     

An Immunohistochemical Study of Localization of the Calcium-Binding Protein Recoverin in Retina of the Newt Pleurodeles waltl

The presence and localization of the calcium-binding protein recoverin, initially found in photoreceptors of the bovine eye, were immunochemically studied in retina of the new Pleurodeles waltl. Polyclonal monospecific antibodies against recoverin were raised and the methods of immunoblotting and indirect immunofluorescence were used. A protein with an apparent molecular mass of 26 kDa was found in the retina extract, which was specifically stained by the antibodies against recoverin. Localization of recoverin was studied on the retina sections: an intense reaction was found in the inner segments and a weak reaction was found in the basal part of the outer segments of photoreceptors and in Landolt's clubs of displaced bipolars. The results we obtained suggest for the first time the presence of recoverin in the retina of a representative of the Urodeles and indicate to interspecific conservativeness of this protein and differences of its localization in the retina photoreceptors in different species. The data obtained open a possibility of using recoverin as a marker protein of photoreceptors and displaced bipolars in studies of retina regeneration in newts.     

Synaptic inputs to the ganglion cells in the tiger salamander retina

The postsynaptic potentials (PSPs) that form the ganglion cell light response were isolated by polarizing the cell membrane with extrinsic currents while stimulating at either the center or surround of the cell's receptive field. The time-course and receptive field properties of the PSPs were correlated with those of the bipolar and amacrine cells. The tiger salamander retina contains four main types of ganglion cell: "on" center, "off" center, "on-off", and a "hybrid" cell that responds transiently to center, but sustainedly, to surround illumination. The results lead to these inferences. The on-ganglion cell receives excitatory synpatic input from the on bipolars and that synapse is "silent" in the dark. The off-ganglion cell receives excitatory synaptic input from the off bipolars with this synapse tonically active in the dark. The on-off and hybrid ganglion cells receive a transient excitatory input with narrow receptive field, not simply correlated with the activity of any presynaptic cell. All cell types receive a broad field transient inhibitory input, which apparently originates in the transient amacrine cells. Thus, most, but not all, ganglion cell responses can be explained in terms of synaptic inputs from bipolar and amacrine cells, integrated at the ganglion cell membrane.     

Organization of the outer plexiform layer of the primate retina: electron microscopy of Golgi-impregnated cells

Golgi-impregnated retinae of rhesus monkeys have been examined by serial section electron microscopy to establish in a quantitative manner the neural connexions in the outer plexiform layer. The results have shown that there are two types of midget bipolar cell, here called the invaginating midget bipolar and the flat midget bipolar. Both types of midget bipolar are exclusive to a single cone. The invaginating midget bipolar has been found to fit a dendritic terminal process into every invagination in the cone pedicle base. The flat midget bipolar has dendritic terminals that make superficial contact on the cone pedicle base. There are twice as many dendritic terminals and points of contact with the cone pedicle on a flat midget bipolar top as compared with an invaginating midget bipolar top. These observations, together with light microscope counts of the numbers of the two types of midget bipolars, suggest that there are two midget bipolars per cone. The diffuse cone bipolar (the flat bipolar) also makes superficial contacts on the cone pedicle base, and serial sections have shown that a flat bipolar contacts about six cones. Rod bipolars connect exclusively to rods and their dendritic terminals always end as one of the central processes that penetrate the invagination. Horizontal cell dendrites end exclusively in cone pedicles and their axon terminals end in rod spherules. The point of contact with both the types of receptor is as the lateral elements of the invaginations. A single small horizontal cell contacts about seven cones and a large horizontal cell contacts about twelve cones. The numbers of contacts per cone pedicle decrease from the centre to the periphery of the horizontal cell's dendritic field, suggesting there is an overlap of four to six horizontal cells onto a single cone pedicle. The horizontal cell axon terminals are too numerous to assess in absolute numbers but there is only one terminal to a given rod spherule from any particular axon.     

Early patterns of neuronal degeneration in the retina of the goldfish after optic nerve sectioning

The early patterns of retinal degeneration were studied in the goldfish after optic nerve sectioning by l.m. and e.m. Beginning on the 2nd postsurgical day there was an initial degeneration of neurons in the ganglion cell and inner nuclear layers of the central retina. Massive ganglion cell degeneration in the whole retina (60%) as well as degeneration of neurons in inner and outer nuclear layer of the peripheral retina was evident around the 7th postsurgical day. The early degenerating cells appeared to be cones and cone bipolars.     

Connexin36 is essential for transmission of rod-mediated visual signals in the mammalian retina

To examine the functions of electrical synapses in the transmission of signals from rod photoreceptors to ganglion cells, we generated connexin36 knockout mice. Reporter expression indicated that connexin36 was present in multiple retinal neurons including rod photoreceptors, cone bipolar cells, and AII amacrine cells. Disruption of electrical synapses between adjacent AIIs and between AIIs and ON cone bipolars was demonstrated by intracellular injection of Neurobiotin. In addition, extracellular recording in the knockout revealed the complete elimination of rod-mediated, on-center responses at the ganglion cell level. These data represent direct proof that electrical synapses are critical for the propagation of rod signals across the mammalian retina, and they demonstrate the existence of multiple rod pathways, each of which is dependent on electrical synapses.     

Synaptic organization and ionic basis of on and off channels in mudpuppy retina. I. Intracellular analysis of chloride-sensitive electrogenic properties of receptors, horizontal cells, bipolar cells, and amacrine cells

Intracellular recordings from receptors, horizontal cells, bipolars, and amacrines have been carried out in the perfused mudpuppy eyecup. The introduction of a chloride-free (c-f) medium results in initial transient potential changes in many cells followed by a slow loss of light-evoked activity of the depolarizing bipolar, the horizontal cell, and the on depolarization of amacrine cells. The hyperpolarizing bipolar remains responsive to light stimulation in a c-f medium, but the antagonistic surround mechanism is abolished. These effects are reversible after returning to a normal ionic medium. The results of this study provide insight into the retinal connections which underlie ganglion cell receptive field organization. It is concluded that the depolarizing bipolar is excitatory to on ganglion cells and is also the pathway for on-excitation of on-off cells. The hyperpolarizing bipolar mediates the off discharge of off and on-off cells. Amacrine cells receive input from both depolarizing and hyperpolarizing bipolar cells. These findings raise the possibility that transmembrane movements of chloride ions are critical for the light responsiveness of horizontal and depolarizing bipolar cell activity.     

Differentiation of the retina and pigment epithelium in the ontogeny of the common frog. 1. The retina

Changes in the ultrastructure of the differentiating retinal cells were studied by means of electron microscopy in Rana temporaria at successive developmental stages. Common features of the onset of differentiation of the retinal cells have been shown: appearance of the granular endoplasmic reticulum elements, of the polysomes, beginning of utilization of the yolk and lipids, elimination of ovarial melanosomes. Later during the differentiation of retinal neurons the protein synthesizing machinery and Golgi complex of these cells develop markedly, the number of mitochondria increases. The differentiation of retina begins from the Müllerian cells (stage 28) which determine the direction of growth of the neuron processes. They are followed by the ganglion cells and photoreceptors (stage 29). The signs of differentiation of the inner nuclear layer neurons become apparent later, in the amacrine and horizontal cells at the same time and in the bipolars later. The main features of neuronal organization of the retina which determine the structural basis of its function of light perception are formed by stage 40.     

Neuronal typology of the thalamic area triangularis of Gallotia galloti (reptilia,sauria)

In a Golgi study of the area triangularis (AT), a rostral nucleus of the ventral thalamus of Gallotia galloti, we have identified four major neuronal types on the basis of their morphological characteristics: medium-sized fusiforms with two processes, medium-sized fusiforms with three or four processes, small bipolars, and small and medium-sized multipolars. These neurons are characterized by a simple morphology and radial arrangement. Cell size varies from small to medium, and all axons project laterally. These characteristics distinguish AT neurons from those of neighboring nuclei. In addition, we found some evidence of differential topographic distribution of each neuronal type within the nucleus. Medium-sized fusiform neurons with two processes are located in the most ventral part, where they constitute the ventral nuclear limit. Small multipolar neurons prevail in the dorsal and ventromedial parts, and in the rest of the nucleus medium-sized neurons, including both fusiform with three or four processes and multipolar types, are normally found. Finally, we discuss a putative homology of the reptilian AT with a part of the mammalian zona incerta.     

Elektronenmikroskopische Befunde zur Differenzierung der Rezeptorzellen und Bipolarzellen der Retina und ihrer synaptischen Verbindungen

Summary The differentiation of the bird's retina is described, paying special attention to the development of synapses and bipolar cells. The structural differentiation of receptor cells and bipolars, the topography and the time sequence of synaptic development has been studied in embryonic material ranging from 6 to 21 days of incubation.Due to the intimate interdigitation of opposing cell membranes in contact with each other, the formation of specialized contacts (synapses) occurs at selected places and shows special features. Their differentiation is characterized by a) accumulation of electrondense material close to the pre- and postsynaptic membrane, b) the presence of large numbers of synaptic vesicles initially perinuclear and moving later in the cytoplasmatic presynaptic processes, c) a special type of synaptic lamella surrounded by vesicles.

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Ich danke der Deutschen Forschungsgemeinschaft und der Volkswagenstiftung für ihre Unterstützung, FräuleinCh. Kiele und FräuleinE. Möhring für die technische Assistenz.