共查询到20条相似文献,搜索用时 46 毫秒
1.
Kuźma-Kozakiewicz M Usarek E Ludolph AC Barańczyk-Kuźma A 《Neurochemical research》2011,36(6):978-985
Due to controversy about the involvement of Dync1h1 mutation in pathogenesis of motor neuron disease, we investigated expression of tau protein in transgenic hybrid mice with
Dync1h1 (so-called Cra1/+), SOD1G93A (SOD1/+), double (Cra1/SOD1) mutations and wild-type controls. Total tau-mRNA and isoforms 0,
1 and 2 N expression was studied in frontal cortex, hippocampus, spinal cord and cerebellum of presymptomatic and symptomatic
animals (age 70, 140 and 365 days). The most significant differences were found in brain cortex and cerebellum, but not in
hippocampus and spinal cord. There were less changes in Cra1/SOD1 double heterozygotes compared to mice harboring single mutations.
The differences in total tau expression and in profile of its isoforms between Cra1/+ and SOD1/+ transgenics indicate a distinct
pathogenic entity of these two conditions. 相似文献
2.
Barańczyk-Kuźma A Usarek E Kuźma-Kozakiewcz M Kaźmierczak B Gajewska B Schwalenstocker B Ludolph AC 《Neurochemical research》2007,32(3):415-421
The work is a continuation of studies on tau expression and alternative splicing in the central nervous system of transgenic
mice harboring human SOD1 with G93A amyotrophic lateral sclerosis (ALS)-associated mutation. Since age is an important risk
factor for ALS, we expanded the studies into younger animals (age 5 and 25 days). We also included cerebellum, a structure
not studied in the context of neurodegeneration in ALS. We found decreased total tau-mRNA expression in hippocampus but not in cortex and spinal cord of young transgenics, and a
lack of exon 10 in 5-day-old mice. In cerebellum, the total tau-mRNA expression was increased in transgenic animals during
the whole period of life, however at the symptomatic stage of ALS (age 120 days) the level of protein was decreased.
It can be concluded that the SOD1 G93A mutation causes early alterations of tau expression in cns, which are not exclusively
restricted to the upper and lower motor neuron. 相似文献
3.
为应用猕猴和树鼩动物模型研究毒品成瘾对神经/免疫系统的影响提供基础数据,对大麻素及阿片受体在正常猕猴和树鼩神经系统和免疫系统的表达进行初步确定.采集正常猕猴和树鼩新鲜组织(皮质、小脑、脑干、海马、脊髓、脾脏),应用半定量逆转录PCR和实时定量PCR的方法检测大麻素与阿片受体mRNA在猕猴和树鼩各组织中的表达情况.猕猴脑部各区包括脾脏均表达大麻索受体1(CNR1),而大麻素受体2(CNR2)只表达于脾脏内.三类阿片受体中,mu(μ)受体表达最为广泛,在以上各组织中均有表达;delta(δ)受体表达的组织最少,只在海马表达;kappa(κ)受体表达介于两者之间,分别在皮质、小脑、脑干、脊髓中表达.在树鼩组织中,CNR1和CNR2表达于整个大脑重要脑区中,且CNR1表达量高于同一区域内CNR2表达的鼍:脾脏中CNR2的表达较高,而CNR1不表达.三类阿片受体只有检测到μ受体在脑部与脾脏表达,且在各个脑区的表达量明显高于脾脏的表达量;δ体和κ受体在被检各个组织中均无表达.总体而言,两种大麻素受体在猕猴和树鼩体内表达情况与人类和鼠的情况类似,而三类阿片受体在猕猴体内表达情况与人类吏为接近.猕猴和树鼩可能可用于人类毒品成瘾的研究;猕猴在某些神经受体的表达更接近人类,其在研究毒品成瘾的机理和对免疫系统的影响方面仍有不可替代的地位. 相似文献
4.
Magdalena Kuźma-Kozakiewicz Agnieszka Chudy Beata Kaźmierczak Dorota Dziewulska Ewa Usarek Anna Barańczyk-Kuźma 《Neurochemical research》2013,38(12):2463-2473
Dynactin is a complex motor protein involved in the retrograde axonal transport disturbances of which may lead to amyotrophic lateral sclerosis (ALS). Mice with hSOD1G93A mutation develop ALS-like symptoms and are used as a model for the disease studies. Similar symptoms demonstrate Cra1 mice, with Dync1h1 mutation. Dynactin heavy (DCTN1) and light (DCTN3) subunits were studied in the CNS of humans with sporadic ALS (SALS), mice with hSOD1G93A (SOD1/+), Dync1h1 (Cra1/+), and double (Cra1/SOD1) mutation at presymptomatic and symptomatic stages. In SALS subjects, in contrast to control cases, expression of DCTN1-mRNA but not DCTN3-mRNA in the motor cortex was higher than in the sensory cortex. However, the mean levels of DCTN1-mRNA and protein were lower in both SALS cortexes and in the spinal cord than in control structures. DCTN3 was unchanged in brain cortexes but decreased in the spinal cord on both mRNA and protein levels. In all SALS tissues immunohistochemical analyses revealed degeneration and loss of neuronal cells, and poor expression of dynactin subunits. In SOD1/+ mice both subunits expression was significantly lower in the frontal cortex, spinal cord and hippocampus than in wild-type controls, especially at presymptomatic stage. Fewer changes occurred in Cra1/SOD1 and Cra1/+ mice.It can be concluded that in sporadic and SOD1-related ALS the impairment of axonal retrograde transport may be due to dynactin subunits deficiency and subsequent disturbances of the whole dynein/dynactin complex structure and function. The Dync1h1 mutation itself has slight negative effect on dynactin expression and it alleviates the changes caused by SOD1G93A mutation. 相似文献
5.
Usarek E Gajewska B Kaźmierczak B Kuźma M Dziewulska D Barańczyk-Kuźma A 《Neurochemical research》2005,30(8):1003-1007
The expression of glutathione S-transferase pi (GST pi), an enzyme responsible for inactivation of a large variety of toxic compounds was studied in spinal
cord, motor and sensory brain cortex obtained from patients who died in the course of amyotrophic lateral sclerosis (ALS).
The studies were performed on formalin-fixed, paraffin-embedded (FFPE) and freshly frozen tissues. The method of RNA isolation
from FFPE was modified. A significant decrease of GST pi-mRNA expression was found in cervical spinal cord and motor brain
cortex of ALS subjects comparing to analogue control tissues (P < 0.01), as well as in motor cortex of ALS subjects comparing to their sensory cortex (P < 0.05). In spinal cords the decrease in GST pi-mRNA expression was accompanied by a decrease of GST pi protein level. Results
indicated lowered GST pi expression on both mRNA and protein levels in the regions of nervous system affected by ALS. The
non-properly inactivated by GST toxic electrophiles and organic peroxides may thus contribute to motor neurons damage. 相似文献
6.
Unaltered D1, D2, D4, and D5 dopamine receptor mRNA expression and distribution in the spinal cord of the D3 receptor knockout mouse 总被引:1,自引:0,他引:1
Hong Zhu Stefan Clemens Michael Sawchuk Shawn Hochman 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2008,194(11):957-962
Dopamine (DA) acts through five receptor subtypes (D1–D5). We compared expression levels and distribution patterns of all
DA mRNA receptors in the spinal cord of wild-type (WT) and loss of function D3 receptor knockout (D3KO) animals. D3 mRNA expression
was increased in D3KO, but no D3 receptor protein was associated with cell membranes, supporting the previously reported lack
of function. In contrast, mRNA expression levels and distribution patterns of D1, D2, D4, and D5 receptors were similar between
WT and D3KO animals. We conclude that D3KO spinal neurons do not compensate for the loss of function of the D3 receptor with
changes in the other DA receptor subtypes. This supports use of D3KO animals as a model to provide insight into D3 receptor
dysfunction in the spinal cord. 相似文献
7.
8.
Neurotrophin-3 plays an important role in survival and differentiation of sensory and sympathetic neurons, sprouting of neurites,
synaptic reorganization, and axonal growth. The present study evaluated changes in expression of NT-3 in the spinal cord and
L6 dorsal root ganglion (DRG), after ganglionectomy of adjacent dorsal roots in cats. NT-3 immunoreactivity increased at 3 days
post-operation (dpo), but decreased at 10 dpo in spinal lamina II after ganglionectomy of L1–L5 and L7–S2 (leaving L6 DRG
intact). Conversely, NT-3 immunoreactivity decreased on 3 dpo, but increased on 10 dpo in the nucleus dorsalis. Very little
NT-3 mRNA signal was detected in the spinal cord, despite the changes in NT-3 expression. The above changes may be related
to changes in NT-3 expression in the DRG. Ganglionectomy of L1–L5 and L7–S2 resulted in increase in NT-3 immunoreactivity
and mRNA in small and medium-sized neurons, but decreased expression in large neurons of L6 DRG at 3 dpo. It is possible that
increased NT-3 in spinal lamina II is derived from anterograde transport from small- and medium-sized neurons of L6 DRG, whereas
decreased NT-3 immunoreactivity in the nucleus dorsalis is due to decreased transport of NT-3 from large neurons in the DRG
at this time. This notion is supported by observations on NT-3 distribution in the dorsal root of L6 after ligation of the
nerve root. The above results indicate that DRG may be a source of neurotrophic factors such as NT-3 to the spinal cord, and
may contribute to plasticity in the spinal cord after injury. 相似文献
9.
Reiko Mizutani Kazuaki Nakamura Shigetoshi Yokoyama Atsushi Sanbe Shinji Kusakawa Yuki Miyamoto Tomohiro Torii Hiroshi Asahara Haruo Okado Junji Yamauchi Akito Tanoue 《Gene expression patterns : GEP》2011,11(1-2):33-40
We previously reported that sorting nexin 3 (SNX3), a protein belonging to the sorting nexin family, regulates neurite outgrowth in mouse N1E-115 neuroblastoma cells. The snx3 gene is disrupted in patients with microcephaly, microphthalmia, ectrodactyly, and prognathism (MMEP) and mental retardation, demonstrating that SNX3 plays an important role in the genesis of these organs during development. The present study was designed to determine the expression pattern of snx3 mRNA, particularly in the mouse central nervous system (CNS), from the embryonic stage to adulthood. Whole mount in situ hybridization of embryonic day (E) 9.5 and 10.5 mouse embryos revealed strong positive signals for snx3 mRNA in the forebrain, pharyngeal arches, eyes, and limb buds. In situ hybridization analyses of embryonic and neonatal brain sections revealed that snx3 mRNA is mainly expressed in the cerebral cortex, hippocampus, piriform cortex, cerebellum, and spinal cord. In adulthood, the expression of snx3 mRNA is observed in the cerebral cortex, hippocampus, piriform cortex, and cerebellar neurons. Thus, snx3 mRNA is expressed during neural development and in adult neural tissues, suggesting that SNX3 may play an important role in the development and function of the CNS. 相似文献
10.
Elevated iron levels are considered to play a role in the neurodegenerative mechanisms that underlie Alzheimer's and Parkinson's
disease. The linkage between hepcidin (Hepc) and ferroportin-1 (FPN1), the divalent metal transporter 1 (DMT1), and ceruloplasmin
(CP) in the brain is unknown. To discern the role of Hepc in regulating the expression of these proteins, we investigated
FPN1, DMT1, and CP protein and mRNA expression in the brain after the intracerebroventricular injection of Hepc. Our results
show that after Hepc injection, expression of FPN1 mRNA and FPN1 protein was inhibited in the cerebral cortex and hippocampus.
Furthermore, we showed a clear change of DMT1 and CP protein and mRNA levels in the brain. The immunohistochemical analysis
revealed an increase of DMT1 and a decrease of CP levels. Semi-quantitative analysis using PCR methods showed an increase
of DMT1(+IRE) mRNA, and a decrease of DMT1(−IRE) mRNA and CP mRNA levels. Since alterations in iron levels in the brain are
causally linked to degenerative conditions such as Alzheimer's disease, an improved understanding of the regulation of iron
transport protein expression such as FPN1, DMT1, and CP could lead to novel strategies for treatments. 相似文献
11.
Region-specific effects of hypothyroidism on the relative expression of thyroid hormone receptors in adult rat brain 总被引:6,自引:0,他引:6
The aim of this study was to determine whether changes in the circulating thyroid hormone (TH) and brain synaptosomal TH content
affected the relative levels of mRNA encoding different thyroid hormone receptor (TR) isoforms in adult rat brain. Northern
analysis of polyA+RNA from cerebral cortex, hippocampus and cerebellum of control and hypothyroid adult rats was performed in order to determine
the relative expression of all TR isoforms. Circulating and synaptosomal TH concentrations were determined by radioimmunoassay.
Region-specific quantitative differences in the expression pattern of all TR isoforms in euthyroid animals and hypothyroid
animals were recorded. In hypothyroidism, the levels of TRα2 mRNA (non-T3-binding isoform) were decreased in all brain regions examined. In contrast the relative expression of TRα1 was increased
in cerebral cortex and hippocampus, whereas in cerebellum remained unaffected. The TRβ1 relative expression in cerebral cortex
and hippocampus of hypothyroid animals was not affected, whereas this TR isoform was not detectable in cerebellum. The TR
isoform mRNA levels returned to control values following T4 intraperitoneal administration to the hypothyroid rats. The obtained results show that in vivo depletion of TH regulates TR gene expression in adult rat brain in a region-specific manner. (Mol Cell Biochem 278: 93–100, 2005) 相似文献
12.
Josephson A Trifunovski A Schéele C Widenfalk J Wahlestedt C Brené S Olson L Spenger C 《Cell and tissue research》2003,311(3):333-342
The three axon growth inhibitory proteins, myelin associated glycoprotein, oligodendrocyte-myelin glycoprotein and Nogo-A, can all bind to the Nogo-66 receptor (NgR). This receptor is expressed by neurons with high amounts in regions of high plasticity where Nogo expression is also high. We hypothesized that simultaneous presence of high levels of Nogo and its receptor in neurons confers a locked state to hippocampal and cortical microcircuitry and that one or both of these proteins must be effectively and temporarily downregulated to permit plastic structural changes underlying formation of long-term memory. Hence, we subjected rats to kainic acid treatment and exposed rats to running wheels and measured NgR mRNA levels by quantitative in situ hybridization at different time points. We also studied spinal cord injuries and quantified NgR mRNA levels in spinal cord and ganglia during a critical postnatal period using real-time PCR. Strikingly, kainic acid led to a strong transient downregulation of NgR mRNA levels in gyrus dentatus, hippocampus, and neocortex during a time when BDNF mRNA was upregulated instead. Animals exposed to running wheels for 3 and 7, but not 1 or 21, days showed a significant downregulation of NgR mRNA in cortex, hippocampus and the dentate gyrus. NgR mRNA levels decreased from high to low expression in spinal cord and ganglia during the first week of life. No robust regulation of NgR was observed in the spinal cord following spinal cord injury. Together, our data show that NgR levels in developing and adult neurons are regulated in vivo under different conditions. Strong, rapid and transient downregulation of NgR mRNA in response to kainic acid and after wheel running in cortex and hippocampus suggests a role for NgR and Nogo-A in plasticity, learning and memory. 相似文献
13.
14.
Atmospheric changes could strongly influence how terrestrial ecosystems function by altering nutrient cycling. We examined
how the dynamics of nutrient release from leaf litter responded to two important atmospheric changes: rising atmospheric CO2 and tropospheric O3. We evaluated the independent and combined effects of these gases on foliar litter nutrient dynamics in aspen (Populus tremuloides Michx) and birch (Betula papyrifera Marsh)/aspen communities at the Aspen FACE Project in Rhinelander, WI. Naturally senesced leaf litter was incubated in litter
bags in the field for 735 days. Decomposing litter was sampled six times during incubation and was analyzed for carbon, and
both macro (N, P, K, S, Ca, and Mg) and micro (Mn, B, Zn and Cu) nutrient concentrations. Elevated CO2 significantly decreased the initial litter concentrations of N (−10.7%) and B (−14.4%), and increased the concentrations
of K (+23.7%) and P (+19.7%), with no change in the other elements. Elevated O3 significantly decreased the initial litter concentrations of P (−11.2%), S (−8.1%), Ca (−12.1%), and Zn (−19.5%), with no
change in the other elements. Pairing concentration data with litterfall data, we estimated that elevated CO2 significantly increased the fluxes to soil of all nutrients: N (+12.5%), P (+61.0%), K (+67.1%), S (+28.0%), and Mg (+40.7%),
Ca (+44.0%), Cu (+38.9%), Mn (+62.8%), and Zn (+33.1%). Elevated O3 had the opposite effect: N (−22.4%), P (−25.4%), K (−27.2%), S (−23.6%), Ca (−27.6%), Mg (−21.7%), B (−16.2%), Cu (−20.8%),
and Zn (−31.6%). The relative release rates of the nine elements during the incubation was: K ≥ P ≥ mass ≥ Mg ≥ B ≥ Ca ≥ S ≥ N ≥ Mn ≥ Cu ≥ Zn.
Atmospheric changes had little effect on nutrient release rates, except for decreasing Ca and B release under elevated CO2 and decreasing N and Ca release under elevated O3. We conclude that elevated CO2 and elevated O3 will alter nutrient cycling more through effects on litter production, rather than litter nutrient concentrations or release
rates. 相似文献
15.
16.
Xiao F Fei M Cheng C Ji Y Sun L Qin J Yang J Liu Y Zhang L Xia Y Shen A 《Neurochemical research》2008,33(9):1735-1748
Src suppressed C kinase substrate (SSeCKS) was identified as a PKC substrate/PKC-binding protein, which plays a role in mitogenic
regulatory activity and has a function in the control of cell signaling and cytoskeletal arrangement. However its distribution
and function in the central nervous system (CNS) lesion remain unclear. In this study, we mainly investigated the mRNA and
protein expression and cellular localization of SSeCKS during spinal cord injury (SCI). Real-time PCR and Western blot analysis
revealed that SSeCKS was present in normal whole spinal cord. It gradually increased, reached a peak at 3 days for its mRNA
level and 5 days for its protein level after SCI, and then declined during the following days. In ventral horn, the expression
of SSeCKS underwent a temporal pattern that was similar with the whole spinal cord in both mRNA and protein level. However,
in dorsal horn, the mRNA and protein for SSeCKS expression were significantly increased at 1 day for its mRNA level and 3 days
for its protein level, and then gradually declined to the baseline level, ultimately up-regulated again from 7 to 14 days.
The protein expression of SSeCKS was further analysed by immunohistochemistry. The positively stained areas for SSeCKS changed
with the similar pattern to that of protein expression detected by immunoblotting analysis. Double immunofluorescence staining
showed that SSeCKS immunoreactivity (IR) was found in neurons, astrocytes, oligodendrocytes of spinal cord tissues within
5 mm from the lesion site. Importantly, injury-induced expression of SSeCKS was co-labeled by active caspase-3 (apoptotic
marker), Tau-1 (the marker for pathological oligodendrocyte) and β-1,4-galactosyltransferase 1 (GalT). All the results suggested
that SSeCKS might play important roles in spinal cord pathophysiology and further research is needed to have a good understanding
of its function and mechanism.
Feng Xiao and Min Fei contributed equally to this work. 相似文献
17.
It is well known that oxidative stress damages bimolecules such as DNA and lipids. No study is available on the morphine-induced
oxidative damage and fatty acids changes in brain and spinal tissues. The aim of this work was to determine the effects of
morphine on the concentrations and compositions of fatty acid in spinal cord segments and brain tissues in rabbits as well
as lipid peroxidation (LP) and glutathione (GSH) levels in cortex brain.
Twelve New Zealand albino rabbits were used and they were randomly assigned to two groups of 6 rabbits each. First group used
as control although morphine administrated to rats in second group. Cortex brain and (cervical, thoracic, lumbar) samples
were taken.
The fatty acids between n:18.0 and 21.0 were present in spinal cord sections and n:10 fatty acids in control animals were
present in the brain tissues. Compared to n:20.0–24.0 fatty acids in spinal cord sections and 8.0 fatty acids in the brain
tissues of drug administered animals. The concentration and composition of the fatty acid methyl esters in spinal cord and
brain tissues was decreased by morphine treatments. LP levels in the cortex brain were increased although GSH levels were
decreased by the morphine administration.
In conclusion, unsaturated fatty acids contents in brain and spinal cord sections and GSH were reduced by administrating spinal
morphine although oxidative stress as LP increased. The inhibition oxidative damage may be a useful strategy for the development
of a new protection for morphine administration as well as opiate abuse. 相似文献
18.
The effects of acute and chronic morphine treatments on the expression of Ca2+/calmodulin dependent protein kinase II (CaMK II) gene in rat brain were investigated using in situ hybridization histochemistry.
Our data showed that repeated, but not single morphine administration, resulted in significant up-regulation of the α-CaMK
II gene expression in hippocampus and frontal cortex. We further studied the time courses of α-CaMK II gene expression in
response to repeated morphine administration. After 3 days of consecutive morphine injections, the α-CaMK II mRNA levels exhibited
a trend of up-regulation, and after 6 days of consecutive morphine injections it increased over 50–60% as compared with the
control group. The α-CaMK II mRNA levels remained high 24 h after the cessation of chronic morphine treatment and returned
to the control level 72 h later. However, changes of α-CaMK II gene levels mentioned above were not detected in amygdala or
piriform cortex. Taken together, our data demonstrate that chronic morphine treatment region-specific up-regulates the levels
of the α-CaMK II gene expression in hippocampus and frontal cortex.
Yuejun Chen, Yan Jiang, Wen Yue contributed equally to this work.
Special issue in honor of Dr. Ji-Sheng Han. 相似文献
19.
Paola Lorenzini Guillermo M. Bisso Stefano Fortuna Hanna Michalek M.D. Ph.D. 《Neurochemical research》1996,21(3):323-329
The effects of metabotropic glutamate receptor (mGluR) agonists on inositol phosphates (IP) accumulation were investigated
in slices of the cerebral cortex, hippocampus, striatum and cerebellum of adult Sprague-Dawley rats. EC50 values for 1S, 3R-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) did not differ significantly between various brain areas
(range 10−5 M), quisqualate was the most potent in all the brain areas (range 10−7−10−6 M), except the cerebellum (10−5 M), ibotenate was the most potent in the striatum (range 10−6 M) and the least potent in the cerebral cortex and hippocampus (range 10−4 M). The efficacy in the four brain areas showed the following trend of ranking order for ACPD and quisqualate: hippocampus
> striatum > cerebral cortex > cerebellum, and for ibotenate: hippocampus > cerebral cortex > striatum > cerebellum, although
the observed differences reached the level of statistical significance only in the case of ACPD (hippocampus and striatum
vs cerebellum) and ibotenate (hippocampus vs cerebellum). Co-incubation of the agonists at maximally effective concentrations
in any pairwise combination resulted in no substantial additivity of IP accumulation. D,L-1-amino-3-phosphonopropionic acid
(AP3) and D,L-2-amino-4-phosphonobutyric acid (AP4) at 0.5 mM concentration antagonized ACPD-induced IP accumulation by about
70 and 45%, respectively, without differences between brain areas. On the other hand, the antagonistic effects ofl-serine-o-phosphate (SOP) at 1 mM concentration were the highest in the hippocampus (75%) and the lowest in the cerebellum (25%). The
comparative data indicate considerable regional receptor heterogeneity, in terms of different ratios of response to the agonists
(but not antagonists, except SOP). There is a robust responsiveness of mGluRs not only in the hippocampus and cerebral cortex,
but also in the striatum which exhibits the highest affinity to both quisqualate and ibotenate. 相似文献
20.