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Query: UNIPROT:P06889 (Mol)
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In rats, the proenkephalin A gene is expressed in proliferating cells of the neuroepithelial zone which later give rise to neocortical neurones and glial cells. Therefore, organotypic cultures of neocortex of newborn rats were used in the present study to examine whether neurones as well as glial cells expressed the gene. The slices were prepared at birth and kept in culture for 7-13 days. Proenkephalin mRNA was visualised by in situ hybridisation, while immunocytochemical staining for MAP-2 and GFAP was used to identify neurones and astroglial cells, respectively. In the analysed slices, only neurones contained proenkephalin mRNA. Activation of protein kinase C with tetradecanoylphorbol acetate (1 mumol/l) caused a strong increase in the number of neurones expressing proenkephalin mRNA. Our results indicate that a large number of neurones is able to express the proenkephalin gene under these conditions. However, only a few of them have a basal expression which is strong enough to be detected with in situ hybridisation.
Brain Res Mol Brain Res 1996 Jan
PMID:Expression of the proenkephalin A gene in organotypic cultures of neocortex from newborn rats. 871 51

B/A4 is the major component of brain amyloid plaque, one of the hallmarks of Alzheimer's disease (AD). B/A4 is a product of proteolytic processing of its precursor, the Alzheimer amyloid precursor protein (APP). Recently, apolipoprotein E (APO-E) has also been shown to be associated with Alzheimer's disease pathology because it is localized to plaques and tangles, and the gene encoding one of the isoforms of APO-E (E4) is associated with late-onset familial and sporadic AD. In addition, APO-E exhibits high affinity for binding to the B-peptide (B/A4). In this study, we have investigated changes in the steady state levels of APP, APO-E, and the astrocyte-specific marker, glial fibrillary acidic protein (GFAP) mRNA in the gerbil hippocampal CA1 region after a 10-min period of bilateral carotid occlusion-induced forebrain ischemia. Following this insult, we observed a loss of 90% of the CA1 neurons by 72 h post-ischemia. The mRNA levels on day 1 through day 7 post-ischemia were quantitated using an image analyzer. There was an increase in the transcription of APO-E and GFAP mRNAs, with the levels of APO-E mRNA being the highest (3-fold increase on day 7 post-ischemia) (P < 0.005). However, we did not see an increase in APP mRNA. In a parallel study [Hall, E.D. et al., Exp. Neurol., 135(1995) 17-27], we have also seen an increase in levels of APO-E and GFAP protein measured by immunocytochemistry. However, in contrast to the lack of an increase in APP mRNA, immunocytochemical measurement of APP did show an increase, perhaps due to delayed translation of previously formed mRNA. We suggest that neuronal injury or insult results in the induction of certain genes (and, therefore, protein synthesis) in the surrounding reactive astrocytes, and these proteins may contribute to post-injury amyloidogenesis.
Brain Res Mol Brain Res 1996 May
PMID:Induction of apolipoprotein E mRNA in the hippocampus of the gerbil after transient global ischemia. 873 65

Several astrocyte gene products, such as enkephalin and glial fibrillary acidic protein (GFAP), are expressed at higher levels under in vitro conditions relative to in vivo. We have observed that cultured glial cells express high basal levels of transcription factors, such as fos-related antigens (Fra), c-Jun, JunD, and cAMP responsive element binding protein (CREB). When neuronal cells are plated on top of the monolayers, the expression of Fra, c-Jun, JunD, and GFAP decreases in the astroglial cells. The DNA binding activity to the AP-1-like sites of the GFAP and proenkephalin genes was examined in these cultures. The protein complex from glial cultures which recognizes the GFAP AP-1 element contained Fra immunoreactivity while the DNA binding from mixed neuronal/glial cultures consists of CREB-immunoreactive proteins. In glial cultures, no binding occurred to the proenkephalin AP-1-like element but a CREB-immunoreactive complex recognized this sequence in the mixed cultures. Thus, with the addition of neurons, both transcription factors and target gene products decrease in astroglial cells. The proteins that compose gene modulatory complexes also change suggesting that regulation of astroglial gene expression is modulated by neurons.
Brain Res Mol Brain Res 1996 Apr
PMID:Transcription factors in primary glial cultures: changes with neuronal interactions. 873 55

1. Evidence is reviewed which shows that a sexually dimorphic nucleus located in the dorsomedial portion of the male ferret's preoptic area/anterior hypothalamus (POA/AH), called the male nucleus of the POA/AH (Mn-POA/AH), develops during fetal life in response to the action of estradiol, which is formed directly in the nervous system from circulating testosterone over the final quarter of a 41-day gestation. 2. Results are summarized which establish that neurons which make up the Mn-POA/AH are born prior to the critical period of estradiol's action in the male brain. Other data show that some radial glial processes, visualized immunocytochemically using antibodies against GFAP, emanate from proliferative zones at the base of the lateral ventricles in a dorsal-ventral orientation, whereas other glial processes emanate laterally from proliferative zones lining the third ventricle. 3. We suggest that at least some neurons which constitute the dorsomedial POA/AH are born in proliferative zones surrounding the lateral ventricles, raising the question of whether estradiol acts in developing males to influence the migration of these neurons along radial glial guides into the Mn-POA/AH. 4. Finally, evidence is summarized showing that excitotoxic lesions of the dorsomedial POA/AH enhance males' preference to approach and interact with another sexually active male, as opposed to an estrous female, when adult subjects are castrated and treated with estradiol benzoate. These data suggest that the sexually dimorphic Mn-POA/AH is an essential part of a CNS circuit which determines heterosexual partner preference in the male ferret.
Cell Mol Neurobiol 1996 Apr
PMID:Estrogenic control of preoptic area development in a carnivore, the ferret. 874 64

Stress proteins, including the 70 kD heat shock protein (HSP70), are induced in injured cells. The present study was designed to characterize the cells injured by global ischemia in rat brain. Adult rats were subjected to forebrain ischemia using bilateral carotid occlusion and systemic hypotension. HSP70 protein immunostaining of brain sections was performed using the C92 monoclonal antibody one day later. HSP70 immunoreactive cells were found in many brain regions including cortex. HSP70 positive neurons in cortex were found in certain laminae, especially layers 2 and 3. Acid fuchsin positive neurons, cells presumed to be dead, were located only in the layers of cortex where HSP70 immunoreactive neurons were found and were infrequent compared to the large number of HSP70 positive neurons. HSP70 immunoreactive glial cells were detected at the margins of ischemic areas, and were mostly OX42 immunoreactive microglia plus some GFAP immunoreactive astrocytes. In some animals HSP70 stained bipolar cells were detected in the striatum and in white matter which may be type 2 astrocytes. These findings confirm that global ischemia injures microglia and astrocytes, and that cells in a given ischemic region sustain varying degrees of injury--from the HSP70 stained neurons that likely survive the ischemia to acid fuchsin stained cells that die.
Brain Res Mol Brain Res 1995 Dec 28
PMID:HSP70 heat shock protein induction following global ischemia in the rat. 875 Aug 37

Angiotensin II (Ang) injected intracerebroventricularly stimulates neurohypophyseal vasopressin (AVP) release into the peripheral circulation. As we have shown previously, central actions of Ang II in the rat forebrain are mediated by the AT1A receptor subtype. In the present paper, we attempted to clarify the cellular localization of the AT1A receptor mRNA in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, in order to reappraise the conflicting data on the nature of the angiotensin II receptor involved in Ang induced vasopressin release. For this purpose, double in situ hybridization was performed using a radioactive AT1A receptor riboprobe and a digoxygenin labeled AVP oligoprobe, and immunohistochemical localization of the glial marker glial fibrillary acidic protein (GFAP) on the same brain slice. The results show neuronal expression of AT1A receptor mRNA mainly in dorsal and medial parvocellular parts of the PVN, its localization in some magnocellular PVN neurons and the absence of its expression in AVP producing neurons either in the PVN or in the SON. Thus, while indirect evidence indicates the involvement of the AT1A receptor subtype in the regulation of CRH and oxytocin release, the stimulation of vasopressinergic neurons is likely due to indirect mechanisms, or to a yet unknown type of angiotensin receptor.
Brain Res Mol Brain Res 1995 Dec 01
PMID:Comparative expression of vasopressin and angiotensin type-1 receptor mRNA in rat hypothalamic nuclei: a double in situ hybridization study. 875 Aug 69

Basic fibroblast growth factor (bFGF) is a polypeptide with potent trophic effects on brain neurons, glia, and endothelial cells. In the current study, we used Northern blotting, in situ hybridization, and immunohistochemical techniques to examine bFGF expression in brain following focal infarction due to permanent occlusion of the proximal middle cerebral artery in mature Sprague-Dawley rats. We found a four-fold increase in bFGF mRNA in tissue surrounding focal infarcts at 1 day after ischemia. In situ hybridization showed that this increase was found throughout several structures in the ipsilateral hemisphere, including frontoparietal, temporal, and cingulate cortex, as well as in caudoputamen, globus pallidus, septal nuclei, nucleus accumbens, and olfactory tubercle. Increased bFGF mRNA expression was associated with cells having the distinct morphological appearance of astroglia in these structures. Immunohistochemistry showed an increase in the size and number of bFGF-immunoreactive (IR) nuclei in these same structures, as well as a shift from nuclear to nuclear plus cytoplasmic localization of immunoreactivity, beginning at 1 day, and peaking at 3 days after ischemia. Double immunostaining identified bFGF-IR cells as astroglia in these structures. (An exception was the piriform cortex, in which both increased bFGF mRNA levels and increased bFGF-IR was found in neurons at 1 day after ischemia). Overall, the peak of increased bFGF expression preceded the peak in expression of the astroglial marker GFAP within the ipsilateral hemisphere. Increased bFGF expression may play an important role in the glial, neuronal, and vascular changes occurring after focal infarction.
Brain Res Mol Brain Res 1996 Jul
PMID:Increased expression of basic fibroblast growth factor (bFGF) following focal cerebral infarction in the rat. 880 11

Although transforming growth factor-beta (TGF-beta) is known to be multifunctional in many physiological systems, its role in the brain is undergoing elucidation. The situation is made more complex by the presence of multiple isoforms, which may be differentially regulated and have various activities in each particular cell type. Because neurons are dependent on neurotrophic factors for survival, we utilized a rat model of transient forebrain ischemia (TFI) to test the hypothesis that TGF-beta isoforms are important in the hippocampal response to injury. Northern blot analysis demonstrated a differential and temporal alteration in TGF-beta isoform expression following TFI. In-situ hybridization experiments revealed that at day 1 following TFI, there was a strong neuronal increase in the TGF beta-1 transcript but a reciprocal decrease in TGF-beta 2 and -beta 3 transcript levels. Immunohistochemical analysis of all three TGF-beta s demonstrated at day 1 following TFI a loss of the immunoreactive proteins in the vulnerable CA-1 hippocampal neurons, but protein preservation in the CA-2-4 neurons which are more resistant to the ischemic insult. At 3-5 days following TFI, significant extraneuronal changes in TGF-beta isoform expression were also detected. Double-staining experiments with antibody to glial fibrillary acidic protein (GFAP) as a marker for astrocytes, and lectin isolectin B4 Griffonia simplicifolia for microglia, demonstrated increased expression of all TGF-beta isoforms in astrocytes but not microglia. Taken together, these results suggest that the TGF-beta peptides in neurons and astrocytes are important endogenous mediators in the CNS response to ischemic injury.
Brain Res Mol Brain Res 1996 Aug
PMID:Differential neuronal and astrocytic expression of transforming growth factor beta isoforms in rat hippocampus following transient forebrain ischemia. 884 7

Schwann cell responses to nerve injury are stimulated, in part, by inflammatory cytokines. This study compares changes in the phenotype of cultured Schwann cells after exposure to the cytokine tumor necrosis factor (TNF)-alpha or the mitogen neu differentiation factor (NDF)-beta. TNF alpha inhibited proliferation in a dose-dependent manner without altering Schwann cell survival. TNF alpha also reduced both gap junctional conductance and Lucifer yellow dye coupling between Schwann cells. Moreover, both Po and glial fibrillary acidic protein (GFAP) immunoreactivity were reduced. By contrast, NDF beta initially had little effect on cell division although it reduced junctional coupling within 8 h. However, by 48 h, NDF beta stimulated proliferation with a concomitant increase in coupling. Dividing Schwann cells (BrdU+) were preferentially dye coupled compared to nondividing cells, indicating an association between proliferation and coupling. Moreover, cultured Schwann cells expressed connexin46 mRNA and protein, and changes in the levels of the protein correlated with the degree of proliferation and coupling. The data thus provide evidence for cytokine-induced modulation of Schwann cell antigenic phenotype, proliferation, and gap junction properties. These observations suggest that enhanced gap junctional communication among Schwann cells after nerve injury could help to coordinate cellular responses to the injury, and that TNF alpha may be a signal which terminates proliferation as well as junctional communication.
Mol Cell Neurosci 1996 Jun
PMID:TNF alpha inhibits Schwann cell proliferation, connexin46 expression, and gap junctional communication. 887 31

Sulfated glycoprotein-2 (SGP-2) is a secreted glycoprotein that along with GFAP has emerged as a prominent molecular marker of neurodegeneration. In the present study, we have evaluated further the relationship between SGP-2, GFAP and neurodegeneration, by examining the effects of LY231617, a potent antioxidant, on expression of SGP-2 and GFAP following four vessel occlusion (4VO). GFAP and SGP-2 RNA levels increased several fold in hippocampus and caudate nucleus in response to 30 min of 4VO. LY231617 treatment markedly attenuated the induction of GFAP RNA in both hippocampus and caudate nucleus, consistent with the significant neuroprotection observed histologically. In contrast, LY231617 treatment blunted SGP-2 RNA expression only in the hippocampus; SGP-2 RNA expression in caudate nucleus was similar to vehicle-treated 4VO, despite the marked attenuation of neuronal damage in both areas by LY231617. These data suggest region-specific differential regulation of SGP-2 and GFAP RNA induction.
Brain Res Mol Brain Res 1996 Nov
PMID:Induction of sulfated glycoprotein-2 (clusterin) and glial fibrillary acidic protein (GFAP) RNA expression following transient global ischemia is differentially attenuated by LY231617. 891 93


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