Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunocytochemistry was used to localize members of the Jun family of immediate-early genes in the forebrain and midbrain of non-stimulated male rats. Antibodies against specific peptide sequences of c-Jun (Ab-1 and Ab-2 from Oncogene Science) and against expressed proteins of JunB and JunD (both from Dr. R. Bravo) revealed widespread and unique distributions for each of these antigens. Charts were made of the distribution of each antigen, and extensive comparisons were made of previous results obtained using in situ hybridization to localize mRNAs for c-jun, junB and junD. Our results indicate a generally favorable comparison between immunoreactivity and distribution of mRNAs for JunB and JunD, but in the case of c-Jun, immunoreactivity and mRNA were comparable only with the Ab-1 antibody. Indeed, the immunocytochemical distribution of the antigen recognized by the c-Jun Ab-2 antibody was distinctly different from that of the other Jun proteins or mRNAs in the rat brain. This antibody (Ab-2) recognized a nuclear protein found extensively in the caudate-putamen, nucleus accumbens, layer II of the olfactory tubercle, the central nucleus of the amygdala, and the lateral division of the bed nucleus of the stria terminalis. Scattered labeled nuclei were found in a few other forebrain structures. Within the caudate-putamen, immunoreactivity was restricted to the matrix compartment, as determined by immunostaining of adjacent sections with the matrix-marker calbindin D28k. Western blots of caudate-putamen demonstrated that this antibody recognized a protein doublet of molecular masses approximately 37 and 34 kDa, distinct from the molecular masses of c-Jun, JunB and JunD. This unique neuroanatomical distribution and molecular mass suggests that this antibody recognizes a previously undescribed Jun-related antigen.
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PMID:Charting of Jun family member proteins in the rat forebrain and midbrain: immunocytochemical evidence for a new Jun-related antigen. 854 92

Adult olivocerebellar axons are capable of vigorous regeneration when provided with growth-permissive environmental conditions. To elucidate the contribution of intrinsic properties to the regenerative capabilities of inferior olivary neurons, we have examined the cellular modifications occurring in these neurons following axotomy and target deprivation in the absence of exogenous growth-promoting influences. Axotomized inferior olivary neurons undergo perikaryal shrinkage, dendritic atrophy and a loss of anti-calbindin immunoreactivity. A conspicuous cell death occurs during the first few weeks after lesion, but about 35% of the affected neurons survive up to 60 days. Coincidentally, a subset of the injured nerve cells become strongly reactive for NADPH diaphorase histochemistry, and this expression is correlated with survival in the medial accessory olive and in the principal olive. In addition, the affected neurons express or maintain the expression of several markers related to regenerative processes, including transcription factors c-Jun, JunD and Krox-24, the growth-associated protein GAP-43 and the developmentally regulated calcitonin gene-related peptide (CGRP). The expression of all these markers is sustained up to two months after lesion, the longest survival time examined. These results show that although adult axotomized inferior olivary neurons undergo severe regressive modifications leading to a conspicuous cell loss, at least a subset of them is resistant to the lesion. In addition, the long-lasting expression of several axon-growth associated markers expressed in these neurons in response to injury reveals that they are endowed with a strong intrinsic regenerative potential.
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PMID:Degenerative phenomena and reactive modifications of the adult rat inferior olivary neurons following axotomy and disconnection from their targets. 962 55

Axon sprouting in dentate granule cells is an important model of structural plasticity in the hippocampus. Although the process can be triggered by deafferentation, intense activation of glutamate receptors, and other convulsant stimuli, the specific molecular steps required to initiate and sustain mossy fiber (MF) reorganization are unknown. The cellular immediate early genes (IEGs) c-fos, c-jun, and zif/268 are major candidates for the initial steps of this plasticity, because they encode transcription factors that may trigger cascades of activity-dependent neuronal gene expression and are strongly induced in all experimental models of MF sprouting. The mutant mouse stargazer offers an important opportunity to test the specific role of IEGs, because it displays generalized nonconvulsive epilepsy and intense MF sprouting in the absence of regional cell injury. Here we report that stargazer mice show no detectable elevations in c-Fos, c-Jun, or Zif/268 immediate early gene proteins (IEGPs) before or during MF growth. Experimental results in stargazer, including (1) a strong IEGP response to kainate-induced convulsive seizures, (2) no IEGP response after prolongation of spike-wave synchronization, (3) no IEGP increase at the developmental onset of seizures or after prolonged seizure suppression, and (4) unaltered levels of the intracellular Ca2+-buffering proteins calbindin-D28k or parvalbumin, exclude the possibility that absence of an IEGP response in stargazer is either gene-linked or suppressed by known refractory mechanisms. These data demonstrate that increased levels of these IEGPs are not an obligatory step in MF-reactive sprouting and differentiate the early downstream molecular cascades of two major seizure types.
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PMID:Nonobligate role of early or sustained expression of immediate-early gene proteins c-fos, c-jun, and Zif/268 in hippocampal mossy fiber sprouting. 980 64

Regional and areal patterns of cell vulnerability (manifested as cell death and neuron loss) and cell sensitivity (as revealed by the presence of intracytoplasmic inclusions) are described in patients with frontotemporal dementia (FTD) and FTD+ motor neuron disease (MND). This is followed by studies geared to learning about possible mechanisms involved in selective neuron loss and studies focused on recognizing the identity of vulnerable populations of local-circuit neurons and the impact of FTD on individual cells as well as on postsynaptic and presynaptic terminals in the frontal cortex. Neuron loss is not associated with increased vulnerability to nuclear DNA fragmentation, and nor is it accompanied by modifications in the expression of the proteins Bcl-2 and Bax, and transcription factors c-Fos and c-Jun, thus suggesting that these proteins are probably not involved in cell death in these disorders. In the frontal and temporal cortices, glutamatergic pyramidal cells and calbindin-D28k-immunoreactive GABAergic local-circuit neurons are lost in the upper cortical layers. Parvalbumin-immunoreactive cells are preserved. In addition, reduction of putative postsynaptic sites (as inferred from the decreased numbers of dendritic branches in both pyramidal and nonpyramidal neurons, and of dendritic spines in pyramidal cells) in remaining neurons of the upper layers, as well as reduction of presynaptic terminals (as suggested by the decreased expression of synaptic vesicle-associated proteins, synaptophysin, synaptotagmin, rab 3a and synapsin 1, and presynaptic plasma membrane proteins SNAP-25 and syntaxin 1) in the upper layers of the frontal cortex, but not of the posterior parietal cortex, demonstrate the combined devastating effects of FTD on cortico-cortical connections.
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PMID:Neurons and their dendrites in frontotemporal dementia. 1043 42

Over the past few years we have studied the plasticity of the adult auditory brainstem in the rat following unilateral changes to the pattern of sensory activation, either by intracochlear electrical stimulation or by deafening. We discovered that modifications to afferent activity induced changes in the molecular composition and cellular morphology throughout the auditory brainstem, including its major centers: the cochlear nucleus complex, the superior olivary complex, and the inferior colliculus. The time window studied ranged from 2 h to over 1 year following induction of changes to afferent activity. The molecular markers employed include the NMDA receptor subunit type 1, the cAMP response element binding protein (CREB), the immediate early gene products c-Fos, c-Jun and Egr-1, the growth and plasticity-associated protein GAP-43 and its mRNA, the calcium binding protein calbindin, the cell adhesion molecule integrin-alpha(1), the microtubule-associated protein MAP-1b, and the neurofilament light chain (NF-L). As a consequence of the specific electrical stimulation of the auditory afferents or the loss of hearing, a cascade of events is triggered that apparently modifies the integrative action and computational abilities of the central auditory system. An attempt is made to relate the diverse phenomena observed to a common molecular signaling network that is suspected to bridge sensory experience to changes in the structure and function of the brain. Eventually, a thorough understanding of these events will be essential for the specific diagnosis of patients, optimal timing for implantation, and suitable parameters for running of a cochlear implant or an auditory brainstem implant in humans. In this report an overview of the results obtained in the past years in our lab is presented, flanked by an introduction into the history of plasticity research and a model proposed for intracellular signal cascades related to activity-dependent plasticity.
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PMID:Activity-dependent plasticity in the adult auditory brainstem. 1184 62

The post-injury responses of traumatic optic neuropathy elicit a number of neuronal reactions in the visual system which have not been fully elucidated. This study aimed to investigate the immediate early gene (IEG) expression in the lateral geniculate nucleus (LGN) following unilateral optic nerve (ON) crush in adult rats with or without contralateral blockade of retinal input, and its indication. Intravitreal injection of the B subunit of cholera toxin was used to label the retinogeniculate projection. In group 1 rats whose unilateral (right eye) ON was crushed, a large induction of c-Jun was observed in the bilateral LGN from 2 h to 3 days post crush. Expression of c-Fos was detected ipsilaterally in cells of the intermediate geniculate nucleus and the medial subdivision of ventral LGN mainly innervated by the intact ON. A majority of c-Fos positive cells were also calbindin D-28k immunoreactive neurons. In group 2 rats whose monocular (left eye) spiking was blocked by tetrodotoxin, a sodium channel blocker, prior to the unilateral (right eye) ON crush, the location of c-Fos expression was observed to be shifted to the side of LGN contralateral to the crush, while the expression pattern of c-Jun resembled the pattern of group 1 rats. Thus, the unilateral ON injury induced significant IEG expression in the LGN may involve different mechanisms, under which the emerging of c-Fos depends upon remaining visual input from the retina, while c-Jun appears independent of visual activity.
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PMID:Differential induction of c-Fos and c-Jun in the lateral geniculate nucleus of rats following unilateral optic nerve injury with contralateral retinal blockade. 1885 93

Compared to other neurons of the central nervous system, autonomic preganglionic neurons are unusual because most of their axon lies in the periphery. These axons are vulnerable to injury during surgical procedures, yet in comparison to peripheral neurons and somatic motor neurons, the impact of injury on preganglionic neurons is poorly understood. Here, we have investigated the impact of axotomy on sacral preganglionic neurons, a functionally diverse group of neurons required for micturition, defecation, and sexual function. We have previously observed that after axotomy, the injury-related transcription factor activating transcription factor-3 (ATF3) is upregulated in only half of these neurons (Peddie and Keast, 2011: PMID: 21283532). In the current study, we have investigated if this response is constrained to particular subclasses of preganglionic neurons that have specific functions or signaling properties. Seven days after unilateral pelvic nerve transection, we quantified sacral preganglionic neurons expressing ATF3, many but not all of which co-expressed c-Jun. This response was independent of soma size. Subclasses of sacral preganglionic neurons expressed combinations of somatostatin, calbindin, and neurokinin-1 receptor, each of which showed a similar response to injury. We also found that in contrast to thoracolumbar preganglionic neurons, the heat shock protein-25 (Hsp25) was not detected in naive sacral preganglionic neurons but was upregulated in many of these neurons after axotomy; the majority of these Hsp25 neurons expressed ATF3. Together, these studies reveal the molecular complexity of sacral preganglionic neurons and their responses to injury. The simultaneous upregulation of Hsp25 and ATF3 may indicate a distinct mechanism of regenerative capacity after injury.
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PMID:Axonal Injury Induces ATF3 in Specific Populations of Sacral Preganglionic Neurons in Male Rats. 3040 44

Neurogenesis in the adult dentate gyrus (DG) of the hippocampus allows the continuous generation of new neurons. This cellular process can be disturbed under specific environmental conditions, such as epileptic seizures; however, the underlying mechanisms responsible for their control remain largely unknown. Although different studies have linked the JNK (c-Jun-N-terminal-kinase) activity with the regulation of cell proliferation and differentiation, the specific function of JNK in controlling adult hippocampal neurogenesis is not well known. The purpose of this study was to analyze the role of JNK isoforms (JNK1/JNK2/JNK3) in adult-hippocampal neurogenesis. To achieve this goal, we used JNK-knockout mice (Jnk1-/-, Jnk2-/-, and Jnk3-/-), untreated and treated with intraperitoneal injections of kainic acid (KA), as an experimental model of epilepsy. In each condition, we identified cell subpopulations at different stages of neuronal maturation by immunohistochemical specific markers. In physiological conditions, we evidenced that JNK1 and JNK3 control the levels of one subtype of early progenitor cells (GFAP+/Sox2+) but not the GFAP+/Nestin+ cell subtype. Moreover, the absence of JNK1 induces an increase of immature neurons (Doublecortin+; PSA-NCAM+ cells) compared with wild-type (WT). On the other hand, Jnk1-/- and Jnk3-/- mice showed an increased capacity to maintain hippocampal homeostasis, since calbindin immunoreactivity is higher than in WT. An important fact is that, after KA injection, Jnk1-/- and Jnk3-/- mice show no increase in the different neurogenic cell subpopulation analyzed, in contrast to what occurs in WT and Jnk2-/- mice. All these data support that JNK isoforms are involved in the adult neurogenesis control.
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PMID:JNK Isoforms Are Involved in the Control of Adult Hippocampal Neurogenesis in Mice, Both in Physiological Conditions and in an Experimental Model of Temporal Lobe Epilepsy. 3068 43