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1.
Suzanne Numan Christine M. Gall Kim B. Seroogy 《Journal of molecular neuroscience : MN》1996,27(2):245-260
Neurotrophins are a group of structurally related polypeptides that support the survival, differentiation, and maintenance
of neuronal populations that express the appropriate high-affinity neurotrophin receptors. Two members of the neurotrophin
family, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), have been shown to increase the survival of dopaminergic
neurons from the ventral midbrain in vitro. Evidence suggests that ventral midbrain neurons might be able to derive support
from these trophic factors in vivo through paracrine or autocrine interactions. Both BDNF and NT-3 mRNAs and their receptor
mRNAs, trkB and trkC mRNAs, respectively, have been localized to the ventral mesencephalon. However, the relative expression levels of the neurotrophins
and their receptor mRNAs throughout ontogeny and in adulthood have not been elucidated. In the present study, the postnatal
developmental expression of BDNF, NT-3, trkB, and trkC mRNAs was analyzed via in situ hybridization to gain insight into the possible role of these factors in vivo. We found that there was a developmental decline
in the expression of BDNF and NT-3 mRNAs in the ventral mesencephalon. In contrast, no alterations in the expression of midbrain
trkB or trkC mRNAs could be discerned. The present results suggest a role for BDNF and NT-3 in the earlier postnatal developmental events
of responsive populations. The continued, albeit lower, expression of the neurotrophins in the ventral mesencephalon in adulthood
also suggests a role for these factors in mature neuronal systems. 相似文献
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Romualdi P Di Benedetto M D'Addario C Collins SL Wade D Candeletti S Izenwasser S 《Journal of molecular neuroscience : MN》2007,31(2):159-164
The interaction of opioids and stimulants is well established; however, the mechanisms that underlie the role that opioid receptors play in psychostimulant action are not. Nociceptin/orphaninFQ (N/OFQ), the endogenous agonist at NOP receptors, attenuates the behavioral effects of cocaine. The effects of cocaine on N/OFQ were examined in rats using immunoautoradiographic and RIA techniques. Chronic administration of cocaine decreased N/OFQ in medial regions of the caudate putamen, the nucleus accumbens shell, and the substantia nigra. These studies show that N/OFQ levels are altered by treatment with cocaine. Furthermore, the changes in N/OFQ parallel those seen for kappa-opioid receptors, suggesting that the interactions between cocaine and these systems might be similar. 相似文献
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RET 1 is a binding site for retinal nuclear proteins located at −136 to −110 bp in the rat opsin promoter, as defined by DNase
protection assays. A similar sequence is found in the upstream flanking regions of many other photoreceptor genes in mammals
and other species, includingDrosophila. A 7-base consensus sequence, CAATTAG, is found in these genes and has the binding activity of the longer RET 1 element.
A 40-kDa protein that binds to RET 1 has been purified over 2 × 105-fold to apparent homogeneity by affinity chromatography. The RET 1 binding activity is first detectable at E18 and increases
during the first two postnatal weeks. At embryonic ages the retarded bands show an altered mobility and at early postnatal
ages two bands are detected, with the adult band increasing and the embryonic band decreasing in intensity. Treatment of early
postnatal retinas with bFGF increased the binding activity in nuclear extracts and caused a shift in migration of the retarded
band to a position characteristic of the embryonic form of the complex. The results support the hypothesis that RET 1-like
elements play an important role in rod photoreceptor development. 相似文献
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This in vitro study investigates and compares the effects of NK3 receptor ligands on the firing rate of rat and guinea pig midbrain dopamine neurons. The findings are discussed in the light of choosing suitable animal models for investigating pharmacological properties of NK3 receptor antagonists, which have been proposed to possess therapeutic activity in neuropsychiatric diseases like e.g. schizophrenia. In vitro midbrain slice preparations of both species were used to record (extracellularly) the firing rates of dopamine neurons located in the substantia nigra (SN) and ventral tegmental area (VTA). Furthermore, the effect of the D2 receptor agonist quinpirole on guinea pig SN and VTA dopamine neurons was investigated. The efficacy of quinpirole in inhibiting guinea pig dopamine neuron firing activity was much less as compared to that of rat dopamine neurons, suggesting a lower dopamine D2 autoreceptor density on the guinea pig neurons. The NK3 receptor agonist senktide induced in subpopulations of rat SN (55%) and VTA (79%) and guinea pig SN (50%) and VTA (21%) dopamine neurons an increase in firing rate. In responsive neurons this effect was concentration‐dependent with EC50 values of 3–5 nM (for both species). The selective NK3 receptor antagonist osanetant (100 nM) was able to partly block the senktide‐induced increase in firing rates of dopamine neurons and shifted the concentration‐response relation curves for senktide to the right (pA2 values were ~7.5). The fractional block of the senktide responses by osanetant appeared to be larger in guinea pig dopamine neurons, indicating that osanetant is a more potent blocker of NK3 receptor‐mediated responses with noncompetitive properties in the guinea pig. Synapse 2011. © 2011 Wiley‐Liss, Inc. 相似文献
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In this study receptors for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) were characterized in chick cerebral cortex by an in vitro binding technique, using 125I-labeled VIP ([125I]-VIP) as a ligand. The specific binding of [125I]-VIP to chick cerebral cortical membranes was found to be rapid, stable, saturable, reversible, and of high affinity. Saturation analysis resulted in a linear Scatchard plot, suggesting binding to a single class of receptor binding sites with high affinity (Kd = 0.21 nM) and low capacity (Bmax = 19.5 fmol/mg protein). The relative rank order of potency of the tested peptides to inhibit [125I]-VIP binding to chick cerebrum was VIP (chicken) > or = VIP (mammalian) > or = PACAP27 > or = PACAP38 > VIP6-28 (mammalian) > PHI (porcine) > neurotensin6-11-chicken VIP7-28 > neurotensin6-11-mammalian VIP7-28 > VIP16-28 (chicken; inactive) approximately secretin (inactive). About 60% of [125I]-VIP-binding sites in chick cerebral cortex were sensitive to Gpp(NH)p, a nonhydrolyzable analog of GTP. It has been concluded that the cerebral cortex of chick, in addition to PAC1 receptors, contains a population of VPAC-type receptors. 相似文献
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Wang XF Yin L Hu JG Huang LD Yu PP Jiang XY Xu XM Lu PH 《Journal of molecular neuroscience : MN》2006,29(1):45-53
The biological effects of interleukin (IL)-1 are mediated by two distinct receptors, the p80 or type I (IL-1RI) and p68 or type II (IL-1RII) receptors. Because IL-1RII has a short, 29-amino acid cytoplasmic domain which may not be sufficient for signaling, there is considerable evidence indicating that IL-1 may signal exclusively through the IL-1RI receptor. Here, we report the expression, distribution, and cellular localization of the IL-1RI protein in the adult rat spinal cord in vivo and embryonic spinal cord in vitro. We found that IL-1RI was expressed in both the gray and white matter throughout the entire length of the spinal cord and was localized in neurons of the anterior horn, astrocytes, oligodendrocytes, and central canal ependymal cells. Interestingly, resting microglia were negative for IL-1RI. In primary cultures obtained from the embryonic day (E) 15 rats, IL-1RI was expressed in neurons, astrocytes, and oligodendrocytes as well as microglia. These data provide both in vivo and in vitro evidence that neurons and glial cells express the IL-1RI proteins. The differential expression of IL-1RI in the developing, but not mature, microglia may indicate the difference of these cells in response to IL-1 stimuli during maturation. The distribution and cellular localization of IL-1RI proteins in the spinal cord provide a molecular basis for understanding the reciprocal interaction between the immune and the central nervous systems. 相似文献
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Kathryn J. Elliott Jay M. Jones Aida I. Sacaan G. Kenneth Lloyd Janis Corey-Naeve 《Journal of molecular neuroscience : MN》1998,10(3):251-260
Nicotinic acetylcholine receptor (nAChR) subunit mRNA expression in the rat substantia nigra (SN) was assayed by semiquantitative
RT-PCR following 6-hydroxydopamine (6-OHDA) lesion of nigrostriatal dopaminergic neurons. Six months after unilateral injection
of 6-OHDA or saline into the SN, total RNA was isolated from ipsilateral and contralateral tissue samples. RT-PCR amplifications
were performed with template titration using primers specific for sequences encoding
PCR products specific for α3, α4, α5, α6, α7, β2, β3, and glutamic acid decarboxylase were detected in the reactions containing
SN RNA. This is the first evidence that α7 may be expressed in the SN. α2 and β4 PCR products were not detected in SN reactions,
although they were observed in hippocampus and thalamus control reactions. A comparison of ipsilateral and contralateral SN
RT-PCR reaction products showed substantial decreases in α5, α6, and β3 product yields following 6-OHDA, but not sham treatment.
Neither the SN of sham-lesioned rats nor the thalamus of 6-OHDA-lesioned rats yielded similar results, indicating that the
effects observed in 6-OHDA-treated SN were not caused by local mechanical damage or a nonspecific response, respectively.
Effects of 6-OHDA treatment on α3, α4, α7, β2, or glutamic acid decarboxylase product yields from SN samples were small or
undetectable. The results suggest that α5, β6, and β3 subunit-encoding mRNAs are expressed at substantially higher levels
in dopaminergic than in nondopaminergic cell bodies in the SN. 相似文献
1. | nAChR α2–α7 and β2–β4 subunits |
2. | Glutamic acid decarboxylase |
3. | Glyceraldehyde 3-phosphate dehydrogenase for normalization of template mass. |
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Bordayo EZ Fawcett JR Lagalwar S Svitak AL Frey WH 《Journal of molecular neuroscience : MN》2005,27(2):185-194
Arachidonic acid (AA), released in response to muscarinic acetylcholine receptor (mAChR) stimulation, previously has been reported to function as a reversible feedback inhibitor of the mAChR. To determine if the effects of AA on binding to the mAChR are subtype specific and whether AA inhibits ligand binding to other G protein-coupled receptors (GPCRs), the effects of AA on ligand binding to the mAChR subtypes (M1, M2, M3, M4, and M5) and to the micro-opioid receptor, beta2-adrenergic receptor (beta2-AR), 5-hydroxytryptamine receptor (5-HTR), and nicotinic receptors were examined. AA was found to inhibit ligand binding to all mAChR subtypes, to the beta2-AR, the 5-HTR, and to the micro-opioid receptor. However, AA does not inhibit ligand binding to the nicotinic receptor, even at high concentrations of AA. Thus, AA inhibits several types of GPCRs, with 50% inhibition occurring at 3-25 MuM, whereas the nicotinic receptor, a non-GPCR, remains unaffected. Further research is needed to determine the mechanism by which AA inhibits GPCR function. 相似文献
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Hannibal J Georg B Hindersson P Fahrenkrug J 《Journal of molecular neuroscience : MN》2005,27(2):147-155
Circadian rhythms are daily adjusted to the environmental day/night cycle by photic input via the retinohypothalamic tract (RHT). Recent studies indicate that melanopsin, a newly identified opsin-like molecule, is involved in the light responsiveness of retinal ganglion cells (RGCs) constituting the RHT. In the present study, we examined the expression of melanopsin at the mRNA and protein level during a day/night cycle and during prolonged periods of light and darkness in the retina of albino Wistar rats. We observed a diurnal change in melanopsin, with mRNA level being highest at early subjective night and protein level highest at late subjective day. Prolonged exposure to darkness significantly increased melanopsin mRNA level as early as the first day, and the expression continued to increase during 5 d in darkness. The decrease in mRNA level during exposure to constant light was slower. After 48 h of light, the melanopsin mRNA level was significantly reduced, and an almost undetectable level was found after 5 d. The induction of melanopsin by darkness was even more pronounced if darkness was preceded by light suppression for 5 d. By use of immunohistochemistry, we showed that darkness increased the amount of protein in the dendritic processes, resulting in a dense network covering the entire retina. Constant light decreased melanopsin immunostaining time dependently, beginning in the distal dendrites and progressing to the proximal dendrites and the soma. Our observations suggest that the intrinsic light-responsive RGCs adapt their expression of the putative circadian photopigment melanopsin to environmental light and darkness. 相似文献
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Jozwiak J Grajkowska W Kotulska K Jozwiak S Zalewski W Zajaczkowska A Roszkowski M Slupianek A Wlodarski P 《Neuromolecular medicine》2007,9(2):117-127
Tuberous sclerosis (TS) is an autosomal dominant disease associated with the formation of usually benign tumors or hamartomas. The disease is connected with upregulation of mammalian target of rapamycin, central regulator of protein translation, which is usually regarded to be activated by Akt kinase. Here, we show for the first time that in all four brain lesions and one angiomyolipoma from TS patients both extracellular signal-regulated kinase (Erk) and p90 ribosomal S6 kinase 1 activation as well as Erk-dependent phosphorylation of p70 ribosomal S6 kinase 1 are markedly elevated whereas Akt, participating in the classical pathway of mammalian target of rapamycin activation is not always activated. Erk activation is also present in TS-derived cell lines. Importantly, Erk inhibition leads to the decrease of proliferation potential of such lines. These results show that Erk is specifically implicated in the pathogenesis of hamartomas. 相似文献
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Madiai F Goettl VM Hussain SR Clairmont AR Stephens RL Hackshaw KV 《Journal of molecular neuroscience : MN》2005,27(3):315-324
Peripheral nerve injury leads to the activation of spinal cord astrocytes, which contribute to maintaining neuropathic (NP) pain behavior. Fibroblast growth factor-2 (FGF-2), a neurotrophic and gliogenic factor, is upregulated by spinal cord astrocytes in response to ligation of spinal nerves L5 and L6 (spinal nerve ligation [SpNL]). To evaluate the contribution of spinal astroglial FGF-2 to mechanical allodynia following SpNL, neutralizing antibodies to FGF-2 were injected intrathecally. Administration of 18 microg of anti-FGF-2 antibodies attenuated mechanical allodynia at day 21 after SpNL and reduced FGF-2 and glial acidic fibrillary protein mRNA expression and immunoreactivity in the L5 spinal cord segment of rats with SpNL. These results suggest that endogenous astroglial FGF-2 contributes to maintaining NP tactile allodynia associated with reactivity of spinal cord astrocytes and that inhibition of spinal FGF-2 ameliorates NP pain signs. 相似文献
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Dysferlin protein analysis in limb-girdle muscular dystrophies 总被引:4,自引:0,他引:4
Vainzof M Anderson LV McNally EM Davis DB Faulkner G Valle G Moreira ES Pavanello RC Passos-Bueno MR Zatz M 《Journal of molecular neuroscience : MN》2001,17(1):71-80
Dysferlin is the protein product of the DYSF gene mapped at 2p31, which mutations cause limb-girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy. To date, nine autosomal recessive forms (AR-LGMD) have been identified: four genes, which code for the sarcoglycan glycoproteins, are associated with both mild and severe forms, the sarcoglycanopathies (LGMD2C, 2D, 2E and 2F). The other five forms, usually causing a milder phenotype are LGMD2A (calpain 3), LGMD2B (dysferlin), LGMD2G (telethonin), LGMD2H (9q31-11), and LGMD21 (19q13.3). We studied dysferlin expression in a total of 176 patients, from 166 LGMD families: 12 LGMD2B patients, 70 with other known forms of muscular dystrophies (LGMD2A, sarcoglycanopathies, LGMD2G), in an attempt to assess the effect of the primary gene-product deficiency on dysferlin. In addition, 94 still unclassified LGMD families were screened for dysferlin deficiency. In eight LGMD2B patients from five families, no dysferlin was observed in muscle biopsies, both through immunofluorescence (IF) and Western blot methodologies, while in two families, a very faint band was detected. Both patterns, negative or very faint bands, were concordant in patients belonging to the same families, suggesting that dysferlin deficiency is specific to LGMD2B. Myoferlin, the newly identified homologue of dysferlin was studied for the first time in LGMD2B patients. Since no difference was observed between patients mildly and severely affected, this protein do not seem to modify the phenotype in the present dysferlin-deficient patients. Dystrophin, sarcoglycans, and telethonin were normal in all LGMD2B patients, while patients with sarcoglycanopathies (2C, 2D, and 2E), LGMD2A, LGMD2G, and DMD showed the presence of a normal dysferlin band by Western blot and a positive pattern on IF. These data suggest that there is no interaction between dysferlin and these proteins. However, calpain analysis showed a weaker band in four patients from two families with intra-familial concordance. Therefore, this secondary deficiency of calpain in LGMD2B families, may indicate an interaction between dysferlin and calpain in muscle. Dysferlin was also present in cultured myotubes, in chorionic villus, and in the skin. Dysferlin deficiency was found in 24 out of a total of 166 Brazilian AR-LGMD families screened for muscle proteins (approximately 14%), thus representing the second most frequent known LGMD form, after calpainopathy, in our population. 相似文献