TY  - JOUR
AB  - Inositol-1,4,5-trisphosphate 3-kinase-A (ITPKA) is the neuronal isoform of ITPKs and exhibits both actin bundling and InsP3kinase activity. In addition to neurons, ITPKA is ectopically expressed in tumor cells, where its oncogenic activity increases tumor cell malignancy. In order to analyze the physiological relevance of ITPKA, here we performed a broad phenotypic screening of itpka deficient mice. Our data show that among the neurobehavioral tests analyzed, itpka deficient mice reacted faster to a hotplate, prepulse inhibition was impaired and the accelerating rotarod test showed decreased latency of itpka deficient mice to fall. These data indicate that ITPKA is involved in the regulation of nociceptive pathways, sensorimotor gating and motor learning. Analysis of extracerebral functions in control and itpka deficient mice revealed significantly reduced glucose, lactate, and triglyceride plasma concentrations in itpka deficient mice. Based on this finding, expression of ITPKA was analyzed in extracerebral tissues and the highest level was found in the small intestine. However, functional studies on CaCo-2 control and ITPKA depleted cells showed that glucose, as well as triglyceride uptake, were not significantly different between the cell lines. Altogether, these data show that ITPKA exhibits distinct functions in the central nervous system and reveal an involvement of ITPKA in energy metabolism.
AU  - Blechner, C.*
AU  - Becker, L.
AU  - Fuchs, H.
AU  - Rathkolb, B.
AU  - Prehn, C.
AU  - Adler, T.
AU  - Calzada-Wack, J.
AU  - Garrett, L.
AU  - Gailus-Durner, V.
AU  - Morellini, F.*
AU  - Conrad, S.*
AU  - Hölter, S.M.
AU  - Wolf, E.*
AU  - Klopstock, T.*
AU  - Adamski, J.
AU  - Busch, D.*
AU  - Hrabě de Angelis, M.
AU  - Schmeisser, M.J.*
AU  - Windhorst, S.*
C1  - 59596
C2  - 48893
CY  - Elsevier House, Brookvale Plaza, East Park Shannon, Co, Clare, 00000, Ireland
TI  - Physiological relevance of the neuronal isoform of inositol-1,4,5-trisphosphate 3-kinases in mice.
JO  - Neurosci. Lett.
VL  - 735
PB  - Elsevier Ireland Ltd
PY  - 2020
SN  - 0304-3940
ER  - 

TY  - JOUR
AB  - The RNA binding motif protein 4 genes RBM4a and RBM4b are located on human chromosome 11q13.2 and encode highly similar proteins of 363 and 359 amino acids, respectively. They contain two RNA recognition motifs (RRMs) and a retroviral-type Zn-finger. RBM4a binds RNA, is involved in alternative splicing and is also a part of the microRNA-processing RISC complex. In particular, RBM4a is involved in exon 10 inclusion of the tau protein. The function of RBM4b is unknown. With new monoclonal antibodies we show that RBM4a is detectable in virtually all tissues and cell lines tested while RBM4b was only found in kidney and liver. Both RBM4a and RBM4b are nuclear phosphoproteins with half-lives of 2.5h and 4.5h, respectively. To our knowledge, this is the first description of RBM4b protein in human tissue. In human brain, expression of RBM4a was strongly up-regulated in cerebellum as compared to forebrain.
AU  - Pfuhl, T.*
AU  - Mamiani, A.*
AU  - Dürr, M.*
AU  - Welter, S.*
AU  - Stieber, J.*
AU  - Ankara, J.*
AU  - Liss, M.*
AU  - Dobner, T.*
AU  - Schmitt, A.*
AU  - Falkai, P.*
AU  - Kremmer, E.
AU  - Jung, V.*
AU  - Barth, S.*
AU  - Grässer, F.A.*
C1  - 1373
C2  - 25850
SP  - 11-15
TI  - The LARK/RBM4a protein is highly expressed in cerebellum as compared to cerebrum.
JO  - Neurosci. Lett.
VL  - 444
IS  - 1
PB  - Elsevier
PY  - 2008
SN  - 0304-3940
ER  - 

TY  - JOUR
AB  - CRF receptor type (CRHR) 1 exerts neuroregulatory control on associative learning processes such as fear and anxiety like behaviour. Using hippocampal slices, we investigated the neuronal excitability in mice lacking CRHR1 (Crhr1(-/-)). Compared to wild-type mice, long-term potentiation (LTP) elicited by 100 pulses at 100Hz was not different. Unexpectedly, at lower frequencies (1, 5 or 10Hz), the resulting synaptic changes in CA1 neurons of Crhr1(-/-) were systematically shifted towards long-term depression (LTD). Furthermore, testing paired-pulse paradigm revealed a GABA receptor-dependent decrease of paired-pulse ratio in Crhr1(-/-). It might be assumed that a lack of CRHR1 induce developmental changes which resulted in altered GABAergic activity, producing attenuated synaptic potentiation after repetitive stimulation and thus favouring LTD in principal neurons. Since CRHR1 are located in GABAergic somata, axons and boutons the activity of these receptor types rather might contribute to the development of the neuronal ability for plasticity like processes on the level of NMDAR subunit composition and GABAergic activity.
AU  - Schierloh, A.*
AU  - Deussing, J.M.*
AU  - Wurst, W.
AU  - Zieglgänsberger, W.*
AU  - Rammes, G.*
C1  - 2287
C2  - 24852
SP  - 82-86
TI  - Corticotropin-releasing factor (CRF) receptor type 1-dependent modulation of synaptic plasticity.
JO  - Neurosci. Lett.
VL  - 416
IS  - 1
PB  - Elsevier [u.a.]
PY  - 2007
SN  - 0304-3940
ER  - 

TY  - JOUR
AB  - Pantothenate kinase-associated neurodegeneration (PKAN) may serve as a model for Parkinson disease (PD) since many PKAN patients suffer from parkinsonism and both conditions lead to iron accumulation in the basal ganglia. We screened the gene coding for pantothenate kinase 2 (PANK2) for sequence variants in PD. We found no mutations in 67 PD patients with affected sibs or early-onset disease. Moreover, PANK2 polymorphisms were not associated with late-onset idiopathic PD in 339 patients. We conclude that PANK2 variants exert, if any, only a very small effect in the genetic risk of PD.
AU  - Klopstock, T.*
AU  - Elstner, M.*
AU  - Lücking, C.B.*
AU  - Müller-Myhsok, B.*
AU  - Gasser, T.*
AU  - Botz, E.
AU  - Lichtner, P.
AU  - Hörtnagel, K.
C1  - 23547
C2  - 31362
SP  - 195-198
TI  - Mutations in the pantothenate kinase gene PANK2 are not associated with Parkinson disease.
JO  - Neurosci. Lett.
VL  - 379
IS  - 3
PB  - Elsevier
PY  - 2005
SN  - 0304-3940
ER  - 

TY  - JOUR
AB  - The feasibility of non-viral gene transfer using liposomes is described for human fetal nigral tissue. Ventral mesencephalic explants from 6 to 12 week old fetuses were grown as free-floating roller tube cultures. For the transfection, a vector coding for beta -galactosidase driven by the Rous Sarcoma Virus promoter was used. The developmental stage of the human tissue, time in vitro and the amount of vector DNA used significantly influenced the transfection efficiency. Optimal transfection results were obtained with tissue from a 10 week old fetus, cultured for 4 days and transfected with mixtures containing 4 mug vector DNA. Histological analysis suggested that a specific population of ventral mesencephalic precursor cells were the target for the gene transfer. This finding might have implications for gene delivery and cell replacement strategies in Parkinson's disease.
AU  - Bauer, M.*
AU  - Meyer, M.*
AU  - Sautter, J.*
AU  - Gasser, T.*
AU  - Ueffing, M.
AU  - Widmer, H.R.*
C1  - 23574
C2  - 31388
SP  - 169-172
TI  - Liposome-mediated gene transfer to fetal human ventral mesencephalic explant cultures.
JO  - Neurosci. Lett.
VL  - 308
IS  - 3
PB  - Elsevier
PY  - 2001
SN  - 0304-3940
ER  -