Thomas Roskoden

Otto-von-Guericke-Universität Magdeburg | OvGU · Institut für Anatomie

While cognitive impairment is common in peripheral diseases such as chronic kidney disease (CKD), mechanistic insights and effective therapies are lacking 1,2 . Organ substitution reverses cognitive impairment, indicating that cognitive impairment driven by peripheral diseases is therapeutically amendable 3,4 . Yet, we lack pharmacological approach...

Introduction and objectives: The Covid-19 pandemic has created major challenges for university teaching. At the beginning of the summer semester 2020, teaching at the Medical Faculty in Magdeburg was almost completely online. Also the course in macroscopic anatomy had to be replaced by virtual e-learning offers. Methods: Videos and photo presentati...

Laboratory rats are frequently used as animal models in research. Since the 1920s rats are bred and reared in laboratories which affect anatomy, physiology, and behavior responses. In the present study we exposed laboratory and wild rats to predator odor and comparatively analyzed their behavioral and physiological responses. In detail, Warsaw Wild...

Plasticity related gene 1 (PRG-1) is a neuron specific membrane protein located at the postsynaptic density of glutamatergic synapses. PRG-1 modulates signaling pathways of phosphorylated lipid substrates such as lysophosphatidic acid (LPA). Deletion of PRG-1 increases presynaptic glutamate release probability leading to neuronal over-excitation. H...

Neuregulins (Nrg) are a gene family that binds to tyrosine kinase receptors of the ErbB family. The protein of Nrg1 is to be involved in heart formation, migration of neurons, axonal pathfinding and synaptic function. A relation between Nrg1 and schizophrenia is assumed. Chronic impairment in schizophrenia is characterized by different positive and...

To investigate (behavioral) disorders or abnormalities it is required to work with laboratory animals such as mice and rats. It is known, that wild rats show a versatile behavioral system compared to laboratory rats. Innate defensive fear behavior including avoidance is part of this behavioral system prey animals need in order to survive and avoid...

Jacob, the protein encoded by the Nsmf gene, is involved in synapto-nuclear signaling and docks an N-Methyl-D-Aspartate receptor (NMDAR)-derived signalosome to nuclear target sites like the transcription factor cAMP-response-element-binding protein (CREB). Several reports indicate that mutations in NSMF are related to Kallmann syndrome (KS), a neur...

Supplemental Material and Methods. (PDF)

Generation of Jacob/Nsmf ko mice. (A) Jacob/Nsmf gene structure and targeting construct. Exons 1–3 were flanked by loxP sites to enable Cre-mediated deletion. (B) Genotyping strategy to differentiate between wild-type (wt), heterozygous (het) and homozygous (ko) mice with specific primers. (C) RT-PCR on wt (lane 1, 2) and Jacob/Nsmf ko mouse mRNA (...

Chromosome preparation of Jacob/Nsmf ko and wt mice testis stained with Giemsa. (A, E) The chromosome preparation shows the normal 40 acrocentric chromosomes (arrowhead 1, mitosis chromosomes during cell division, 2, immature sperm cell, 3, spermatogonia). (B, F) Arrowhead 4 shows condensation of chromosomes during Metaphasis I—Pachytene. (C, G) Ar...

Volumetric analysis of various brain structures using manganese-enhanced MRI. (A) Comparison of the total brain volume and the volume of different brain structures of Jacob/Nsmf ko (-/-)and wt (+/+) littermates. Significant difference between the two groups (p<0.05) is indicated by an asterisk. (B) 3D surface rendering of the striatum in wt (+/+) a...

Distribution of tyrosine hydroxylase immunoreactivity fibers in the dorsal hippocampus of wt and Jacob/Nsmf ko mice. For overview and quantification see S8F–S8J Fig. From top down images from CA1, DG and CA3 layers (CA1 and CA3: Or, Rad, LMol; DG: Mol, ML) of each genotype are shown (scale bar 50 μm). The exemplary images are taken from the same mo...

Jacob/Nsmf ko mouse cortical primary neurons show no alternations in dendritic tree complexity and synapse number. (A) Representative micrographs of wt and Jacob/Nsmf ko cortical neurons immuno-stained with MAP2 at DIV10. For sholl analysis the number of dendritic intersections of wt and Jacob/Nsmf ko cortical neurons was plotted against the distan...

TrkB and pTrkB levels are unchanged in the hippocampus of Jacob/Nsmf ko and wt mice. Immunoblots of hippocampal lysates from 6 wt and 6 Jacob/Nsmf ko animals: (A) Anti Trk-B antibody detects both full-length (FL) and truncated (Trunc) forms of TrkB. (B) Anti phosphoTrk antibody. The quantification of levels of TrkB (C), pTrk (D) normalized to actin...

LTP cannot be rescued following BDNF application in slices of Jacob/Nsmf ko mice. Application of 100ng/ml BDNF during tetanus has no effect on LTP in ko mice. The arrows indicate high frequency stimulus (HFS) lasting 1s at 100Hz, 3x HFS. The horizontal bar indicates the period during BDNF was added into the bath solution. Data are represented as me...

Results of different behavioral parameters during the exposition of Jacob/Nsmf ko and wt mice to TMT or DEP. Data are presented as mean ± SEM, data analysis of individual mice from both genotypes was performed using multivariate analyses of variance (MANOVA’s) with GENOTYPE and ODOR as the between-subject factors. (PDF)

Jacob/Nsmf ko mice do not show signs of anosmia or hyposmia. To test anosmia or hyposmia in Jacob/Nsmf ko mice and wt controls (n = 8, males) the animals were singly placed into the center of the box. Freezing behavior was analyzed for 15 min either to TMT or DEP that was pipetted on filter papers and administered through a side lid. Odor expositio...

Jacob/Nsmf ko mice display an enlargement of the dentate gyrus projection compared to wt mice. Representative TIMM-stained hippocampal area in wt (A) and Jacob/Nsmf ko mice (B). In Jacob/Nsmf ko mice the complete DG is significant enlarged compared to wt mice. (C-E) Morphometry in the hippocampus. (C) Significant differences could be detected in co...

Distribution of tyrosine hydroxylase immunoreactivity in the striatal complex and ventral tegmental area (VTA) of wt (+/+) and Jacob/Nsmf ko (-/-) mice. (A, B) In the striatum (Bregma 1.18 mm) the dotted lines indicate the boundaries of the core (AcbCore) and shell (AcbShell) regions of the nucleus accumbens. Square sample fields (200 x 200 μm) wer...

Differences in expression of GFP under control of the Bdnf I+II promoter in Jacob/Nsmf ko and wt hippocampal neurons. (A) DIV10 hippocampal neurons were transfected with construct overexpressing GFP under Bdnf I+II promoter. After 24h of expression and treatment with BDNF, cultures were fixed and confocal images were acquired. (B) In Jacob/Nsmf ko...

Primary hippocampal neurons do not show extracellular Jacob localization. (A) Primary neurons (DIV7) express Jacob intracellularly (permeabilized), but not extracellularly (B) (Jacob live) as there is no higher staining than in secondary antibody controls (C). MAP2 staining was included to outline dendrites. (D) Live-staining of Prion protein (DIV7...

Characterization of the pan-Jacob antibody employed. (A) pan-Jacob antibodies were generated against rat N-terminal peptide aa 187–203 corresponding to rat Jacob sequence which is slightly different from the mouse Jacob sequence. Antibodies do recognize heterologously expressed rat WT-Jacob-GFP, but not the mouse WT-Jacob-GFP protein. (B) Antibodie...

Acute BDNF administration has no effect CREB immunofluorescence levels in mouse hippocampal primary neurons. (A, B) Following bath application of BDNF (100ng/ml) at DIV10 the total nuclear CREB levels are unchanged in Jacob/Nsmf ko and wt hippocampal neurons. Scale bar is 20μm. (TIF)

Social interaction test with Jacob/Nsmf ko and wt mice. Data are presented as mean ± SEM, using unpaired t-tests (Welch’s test); data collected from pairs of mice of each genotype were analyzed. (PDF)

General brain morphology of Jacob/Nsmf ko mice is normal. Microphotographs of Nissl-stained coronal sections displaying the brain morphology of wt (+/+) and Jacob/Nsmf ko (-/-) mice at this level (Bregma -1.94 mm). There are no differences in general morphology between both genotypes (scale bar 1 mm). (TIF)

Jacob/Nsmf ko mice display hyperactive behavior in the open field. (A) Motor behavior of Jacob-deficient mice and wt littermates (n = 12, each genotype, both sexes) was analyzed on the rotarod. (B, C) Spontaneous behavior was tested in the open field and revealed significant differences between wt and Jacob/Nsmf ko mice towards speed and distance c...

Jacob/Nsmf ko mice do not show impaired auditory cortex-dependent discrimination learning in the shuttle box compared to wt mice. Male mice (Jacob/Nsmf ko: n = 10, wt littermates: n = 8) were trained in a two-way shuttle box GO/NO-GO task to discriminate between sequences of rising (4–8 kHz, CS+) and falling (8–4 kHz, CS-) frequency modulated tones...

Jacob/Nsmf ko mice have normal base line, paired pulse facilitation and basal synaptic transmission. (A) Baseline stability experiments revealed no difference between wt and Jacob/Nsmf ko mice. (B) Paired-pulse facilitation ratio (PPF ratio, P2/P1) was plotted against different inter-pulse intervals as second divided by first fEPSP. (C) Input-outpu...

Simplification of Jacob-deficient mouse neurons can be rescued by BDNF but not by NGF or boiled BDNF. Jacob/Nsmf ko mouse hippocampal neurons and wt neurons were treated with BDNF, boiled BDNF or NGF (all 100 ng/ml) at DIV2 and DIV6, fixed at DIV10 and stained for MAP2. (A) Graphs representing the number of dendritic intersections of wt and jacob/n...

Plasticity-related gene-1 (PRG-1) is a brain-specific protein that modulates glutamatergic synaptic transmission. Here we investigated the functional role of PRG-1 in adolescent and adult mouse barrel cortex both in vitro and in vivo. Compared with wild-type (WT) animals, PRG-1-deficient (KO) mice showed specific behavioral deficits in tests assess...

The plasticity-related gene 1 (PRG1) modulates bioactive lipids at the postsynaptic density and is a novel player in neuronal plasticity and regulation of glutamatergic transmission at principal neurons. PRG1, a neuronal molecule, is highly expressed during development and regeneration processes at the postsynaptic density, modulates synaptic lysop...

Innate defensive fear behavior, which includes risk assessment and avoidance, is part of the behavioral system of prey animals such as rats in order to survive predator threats and avoid potential endangerment. TMT, a constituent of fox feces, is a commonly used predator odor to induce robust fear behavior in mice and rats. Predator urine is also f...

The synthetic predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) was used to induce in- nate fear in male GAD67 mice and behavioral changes were correlated with c-fos mRNA levels as marker for neuronal activation to reveal underlying activated fear circuits. Results show the same amount of increased freezing and decreased rearing and groom...

Stress affects learning and there are both facilitating and impairing actions of stressors on memory processes. Here we investigated the influence of acute exposure to 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), an ethological relevant stressor for rodents, on spatial memory formation and performance in a radial arm maze (RAM) task and studied TMT...

Altered neuroplasticity contributes to the pathophysiology of schizophrenia. However, the idea that antipsychotics may act, at least in part, by normalizing neurogenesis has not been consistently supported. Our study seeks to determine whether hippocampal cell proliferation is altered in adult rats pretreated with ketamine, a validated model of sch...

The neurotrophic factors play an important role in the maintenance of neurone viability and neuronal communication which are considered to be altered in schizophrenia. Subchronic application of ketamine (Ket) was found to be a useful model in schizophrenia research. To further validate this model the mRNA levels of neurotrophic factors NGF, NT-3, a...

In the present study, newborn rats were implanted with corticosterone (CORT) containing polymers at postnatal day 0 (releasing rate 320-80 microg CORT/kg body weight and day). Controls received a CORT-free implant. All implants were removed at postnatal day 12. At the age of 16-20 weeks, these animals were tested for emotional behavior using an ele...

In the present study new-born rats were treated with corticosterone (CORT) between postnatal days 1 and 12. At the age of 16-20 weeks, these animals were tested for spatial learning capacity using an eight-arm radial maze. After behavioral testing, density of cholinergic fibers and sizes of the mossy fiber terminal fields in the hippocampus and num...

The central nucleus of the amygdala (CeA) is generally regarded as a control nucleus of subcortical target systems. Due to its widespread projections to different brain areas it is able to modulate emotional behavior of the organism. However, it is still not clear whether single neurons of the CeA project to different areas or to one target area. I...

The principal glucocorticoid in rats, corticosterone, interacts with neurons in the limbic system and leads to morphological and behavioral changes. Putative corticosterone-triggered mediators are neurotrophins. In the present study we investigated the effects of early postnatal corticosterone treatment in rats on neurotrophic factors of the nerve...

There is evidence that morphological alterations concerning deficiency or abundance of thyroid hormones (TH) may be mediated by brain-derived neurotrophic factor (BDNF). It has been demonstrated that the mRNA-expression of BDNF is increased after TH-treatment during the first postnatal weeks. After transient treatment of newborn rats with thyroxine...

The amygdala is a brain region involved in the regulation of anxiety-related behavior. The purpose of this study was to correlate anxiety-related behavior of inbred mouse strains (BA//c, BALB/cJ, C3H/HeJ, C57BL/6J, CPB-K, DBA/2J, NMRI) to receptor binding in the amygdala. Binding site densities of receptors (NMDA, AMPA, kainate, GABA(A), serotonin,...

Newborn rats were treated daily with thyroid hormone (TH) until postnatal day 12. In the adult animals we measured the densities of glutamatergic (N-methyl-D-aspartate (NMDA), amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), kainic acid (KA)), cholinergic (muscarinic subtype 1 and 2 (M1, M2)), gamma-aminobutyric acid (GABA)ergic (GABA(A))...

Early postnatal application of thyroid hormones to rats results in morphological changes of the septo-hippocampal cholinergic and the hippocampal mossy fiber systems. Modulation in the expression of either neurotrophins and/or their receptors is postulated to be involved in these effects. In a recent study, we showed that, after thyroxine applicati...

Early postnatal application of thyroid hormones to rats results in morphological changes in septum and hippocampus. Modulation in the expression of either neurotrophins and/or their receptors is postulated to be responsible for these effects. In the present study we tested whether thyroxine administration leads to changes in the expression of neuro...

The immunolocalization of cathepsin L in the hypothalamus of normal rats was compared with the distribution of the enzyme in streptozotocin-treated animals and in vasopressin-deficient rats (Brattleboro strain). In rats with a normal metabolic status the neurons of magnocellular nucl. supraopticus and paraventricularis stood out by intense immunost...

Immunohistochemically detectable cathepsin L was demonstrated in rat brain by means of a monospecific, polyclonal antiserum. Sternberger's unlabeled immunoenzyme technique was employed. Cathepsin L immunoreactive material was found in multiple hypothalamic and brain stem neurocytes as well as in some hippocampal and neocortical nerve cells. Catheps...