Cyclooxygenases-2 (COX-2) is not only related to inflammation but also plays critical roles in brain development and synaptic
signaling. In the present study, we investigated age-related changes in COX-2 immunoreactivity and protein levels in the gerbil
hippocampus. In the hippocampal CA1 region (CA1) and dentate gyrus (DG), weak COX-2 immunoreactivity was observed at postnatal
month 1 (PM 1), and COX-2 immunoreactivity was markedly increased at PM 18 and 24. In the CA2/3, COX-2 immunoreactivity was
strong at PM 1. COX-2 immunoreactivities in the PM 3, 6 and 12 groups were decreased compared to that in the PM 1 group, and
it was increased at PM 18 and 24. In addition, age-related changes in COX-2 levels were similar with immunohistochemical results
in the CA2/3. These results suggest that COX-2 immunoreactivity and levels were high in the hippocampus of aged gerbils. 相似文献
Age-dependent studies on oligodendrocytes, which are the myelinating cells in the central nervous system, have been relatively
less investigated. We examined age-dependent changes in Rip immunoreactivity and its protein level in the gerbil hippocampus
during normal aging using immunohistochemistry and Western blot analysis with Rip antibody, an oligodendrocyte marker. Rip
immunoreactivity and its protein level in the hippocampal CA1 region significantly increased at postnatal month 3 (PM 3).
Thereafter, they decreased in the hippocampal CA1 region with age. At PM 24, Rip immunoreactive processes in the hippocampal
CA1 region markedly decreased in the stratum radiatum. In the hippocampal CA2/3 region and dentate gyrus, the pattern of changes
in Rip immunoreactivity and its protein level was similar to those in the hippocampal CA1 region; however, no significant
changes were found in the CA2/3 region and dentate gyrus at various age stages. These results indicate that Rip immunoreactivity
and protein level in the hippocampal CA1 region decreases significantly at PM 24 compared to the CA2/3 region and dentate
gyrus. 相似文献
The hippocampus is associated with learning and memory function and shows neurochemical changes in aging processes. Calbindin
D-28k (CB) binds calcium ion with a fast association rate. We examined age-related changes in CB immunoreactivity and its
protein level in the gerbil hippocampus during normal aging. In the hippocampal CA1 region (CA1) and CA2, CB immunoreaction
was found in some neurons in the stratum pyramidale (SP) at postnatal month 1 (PM 1). CB immunoreactivity in neurons was markedly
increased at PM 3. Thereafter, CB immunoreactivity was decreased with time: CB-immunoreactive (+) neurons were fewest at PM 24. In the CA3, a few CB+ neurons were found only in the SP at PM 1 and in the stratum radiatum at PM 18 and 24. In addition, mossy fibers were stained
with CB at PM 1. CB immunoreactivity in mossy fibers was markedly increased at PM 3, thereafter it was decreased with time.
In the dentate gyrus, many granule cells (GC) in the granule cell layer were stained with CB at PM 1. CB immunoreactivity
in GC was markedly increased at PM 3, thereafter CB immunoreactivity was decreased with time. In Western blot analysis, CB
protein level in the gerbil hippocampus was highest at PM 3, thereafter CB protein levels were decreased with time. This result
indicates that CB in the gerbil hippocampus is abundant at PM 3 and is decreased with age. 相似文献
Calretinin (CR)-immunoreactive interneurons are well known as the interneuron specific interneurons in the hippocampus. CR-immunoreactive
neurons form cellular network and regulate the activity of other GABAergic inhibitory interneurons in the hippocampus. In
the present study, we investigated age-related changes in CR-immunoreactive neurons and protein levels in the gerbil hippocampus
during normal aging. In all subregions of the gerbil hippocampus, the number of CR-immunoreactive neurons was significantly
decreased in the postnatal month 6 (PM 6) group compared to that in the PM 1 group. Thereafter, CR-immunoreactive neurons
were decreased with age. In addition, the number of CR-immunoreactive cells in the subgranular zone were significantly decreased
in the PM 6 group. We also observed that CR protein levels were decreased gradually with age. These results indicate that
both CR immunoreactivity and its protein level were decreased with age in the gerbil hippocampus during normal aging. 相似文献
Oxidative stress is one of predisposing factors to age-related neurodegeneration in the brain. In particular, thiol-containing
groups are susceptible to oxidative stress, which induces the formation of the disulfide bond and/or hyperoxidized form of
thiol-containing proteins. We observed the protein thiol levels in the hippocampal homogenates and also investigated changes
in hyperoxidized form of peroxiredoxin (Prx–SO3) immunoreactivity and proteins levels in the gerbil hippocampal subregions during normal aging. Levels of total thiol, non-protein
thiol, and protein thiol were decreased in the hippocampal homogenates with age. At post-natal month 1 (PM 1), pyramidal and
non-pyramidal cells in the hippocampal CA1 region (CA1) showed Prx–SO3 immunoreactivity. Prx–SO3 immunoreactivity in the cells was decreased by PM 12, thereafter, Prx–SO3 immunoreactivity in the cells increased again with age. In the CA2/3, Prx–SO3 immunoreactivity in pyramidal cells was not significantly changed; however, the immunoreactivity in pyramidal cells was very
low at PM 12. Prx–SO3 immunoreactivity in the dentate gyrus (DG) was distinctly changed during aging. At PM 1, Prx–SO3 immunoreactivity in granule and polymorphic cells was weak and strong, respectively. The immunoreactivity in the neurons
was decreased with age, not shown in any neurons at PM 12. Thereafter, Prx–SO3 immunoreactivity increased again with age. In addition, Prx–SO3 protein level in the hippocampus was lowest at PM 12. These results suggest that thiol-containing proteins are changed during
aging and Prx–SO3 immunoreactivity was different according to cells in the hippocampal subregion during aging. 相似文献
Doublecortin (DCX), a microtubule-associated protein, specifically expresses in neuronal precursors. This protein has been
used as a marker for neuronal precursors and neurogenesis. In the present study, we observed differences in DCX immunoreactivity
and its protein levels in the hippocampal dentate gyrus between adult and aged dogs. In the adult dog, DCX immunoreactive
cells with well-stained processes were detected in the subgranular zone of the dentate gyrus. Numbers of DCX immunoreactive
cells in the dentate gyrus of the aged dog were significantly decreased compared to those in the adult dog. DCX immunoreactive
cells in both adult and aged dog did not show NeuN (a marker for mature neurons) immunoreactivity. NeuN immunoreactivity in
the aged dog was poor compared to that in the adult dog. DCX protein level in the aged dentate gyrus was decreased by 80%
compared to that in the adult dog. These results suggest that the reduction of DCX in the aged hippocampal dentate gyrus may
be involved in some neural deficits related to the hippocampus. 相似文献
Abstract: Gerbils ( Meriones unguiculatus ) are known for their seizure sensitivity, which is dependent on an intact perforant path from the entorhinal cortex to the hippocampus. In contrast with other species, the perforant path in gerbils contains parvalbumin, a cytosolic high-affinity calcium-binding protein. Parvalbumin is known to be present in a subpopulation of GABA-containing neurons and is thought to be responsible for their physiological characteristics of fast spiking activity and lack of spike adaptation. Therefore, the question arose of whether this projection in gerbils is GABAergic or glutamatergic as in other species. In a first approach to this question, the effect of lesioning the origin of the perforant path, the entorhinal cortex, on levels of GABA and glutamate was determined by enzymatic-luminometric assay in single layers of the dentate gyrus of lyophilized brain sections. Parallel sections were cryofixed using an acidified acetone-formaldehyde mixture at -20°C for 48 h, and subsequently stained for parvalbumin immunocytochemistry. Seven days after ablation of the entorhinal cortex, parvalbumin staining was undetectable in the termination zone of the perforant path, the outer two-thirds of the stratum moleculare. In parallel, glutamate content was reduced to 80% of controls (and of the unoperated contralateral side) but unchanged in the inner third of the stratum moleculare and in stratum granulare. GABA content was not significantly altered by the lesion. From these results, we conclude that in the gerbil as in other species, the perforant path contains glutamate. The association of glutamate with parvalbumin suggests, however, that in the gerbil the calcium-dependent release of the transmitter is carefully controlled in the entorhinal perforant path. 相似文献
1. We investigated the immunohistochemical alterations of BDNF, NGF, HSP 70 and ubiquitin in the hippocampus 1 h to 14 days
after transient cerebral ischemia in gerbils. We also examined the effect of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)
reductase inhibitor pitavastatin against the changes of BDNF, NGF, HSP 70 and ubiquitin in the hippocampus after cerebral
ischemia in the hippocampus after ischemia.
2. The transient cerebral ischemia was carried out by clamping the carotid arteries with aneurismal clips for 5 min.
3. In the present study, the alteration of HSP 70 and ubiquitin immunoreactivity in the hippocampal CA1 sector was more pronounced
than that of BDNF and NGF immunoreactivity after transient cerebral ischemia. In double-labeled immunostainings, BDNF, NGF
and ubiquitin immunostaining was observed both in GFAP-positive astrocytes and MRF-1-positive microglia in the hippocampal
CA1 sector after ischemia. Furthermore, prophylactic treatment with pitavastatin prevented the damage of neurons with neurotrophic
factor and stress proteins in the hippocampal CA1 sector after ischemia.
4. These findings suggest that the expression of stress protein including HSP 70 and ubiquitin may play a key role in the
protection against the hippocampal CA1 neuronal damage after transient cerebral ischemia in comparison with the expression
of neurotrophic factor such as BDNF and NGF. The present findings also suggest that the glial BDNF, NGF and ubiquitin may
play some role for helping surviving neurons after ischemia. Furthermore, our present study indicates that prophylactic treatment
with pitavastatin can prevent the damage of neurons with neurotrophic factor and stress proteins in the hippocampal CA1 sector
after transient cerebral ischemia. Thus our study provides further valuable information for the pathogenesis after transient
cerebral ischemia.
The first two authors contributed equally 相似文献
Oxidative stress is a major pathogenic event occurring in several brain disorders and is a major cause of brain damage due
to ischemia/reperfusion. Thiol proteins are easily oxidized in cells exposed to reactive oxygen species (ROS). In the present
study, we investigated transient ischemia-induced chronological changes in hyperoxidized peroxiredoxins (Prx-SO3) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH-SO3) immunoreactivity and protein levels in the gerbil hippocampus induced by 5 min of transient forebrain ischemia. Weak Prx-SO3 immunoreactivity is detected in the hippocampal CA1 region of the sham-operated group. Prx-SO3 immunoreactivity was significantly increased 12 h and 1 day after ischemia/reperfusion, and the immunoreactivity was decreased
to the level of the sham-operated group 2 days after ischemia/reperfusion. Prx-SO3 immunoreactivity in the 4 days post-ischemia group was increased again, and the immunoreactivity was expressed in glial components
for 5 days after ischemia/reperfusion. GAPDH-SO3 immunoreactivity was highest in the CA1 region 1 day after ischemia/reperfusion, the immunoreactivity was decreased 2 days
after ischemia/reperfusion. Four days after ischemia/reperfusion, GAPDH-SO3 immunoreactivity increased again, and the immunoreactivity began to be expressed in glial components from 5 days after ischemia/reperfusion.
Prx-SO3 and GAPDH-SO3 protein levels in the ischemic CA1 region were also very high 12 h and 1 day after ischemia/reperfusion and returned to the
level of the sham-operated group 3 days after ischemia/reperfusion. Their protein levels were increased again 5 days after
ischemia/reperfusion. In conclusion, Prx-SO3 and GAPDH-SO3 immunoreactivity and protein levels in the gerbil hippocampal CA1 region are significantly increased 12 h-24 h after ischemia/reperfusion
and their immunoreactivity begins to be expressed in glial components from 4 or 5 days after ischemia/reperfusion. 相似文献
Abstract: Changes in the ganglioside long-chain base (LCB) composition in rat cerebellar granule cells in culture were studied during differentiation and aging. The total native ganglioside mixtures, extracted from the cells maintained in culture up to 22 days, were fractionated by reversed-phase HPLC, each ganglioside homogeneous in the oligosaccharide chain as well as in the LCB being quantified. Two main LCBs were components of the ganglioside species of cultured cells, the C18:1 LCB and the C20:1 LCB. The content of C20:1 ganglioside molecular species was low and quite constant during differentiation, comprising ∼8% of the total ganglioside species content, the C20:1 LCB appearing to be represented more in the ganglioside of the "b series" (GD1b, GT1b, and GQ1b) than in the "a series" (GM1 and GD1a). During aging in culture, for 8–22 days, the content of the C20:1 species of all gangliosides increased, being more pronounced for GM1 and GD1a. 相似文献
One of the most vulnerable areas to ischemia or hypoglycemia is CA1 hippocampal region due to pyramidal neurons death. Glutamate receptors are involved together with protein-kinase C and nitric oxide synthase. Long-term potentiation (LTP) is generated in anoxic or hypoglycemic conditions via activation of NMDA while inhibition of these receptors atenuates this response. Protein-kinase C and nitric oxide synthase are involved in anoxic LTP mechanism. Postischemic neurons are hyperexcitable in CA3 area while CA1 pyramidal neurons degenerate and dissapear. Changes of glutamate receptors triggered by ischemia and hypoglycemia are discussed in this review. 相似文献
Age‐related cognitive decline and neurodegenerative diseases are associated with less functional neurogenic niches. It has been recently shown that aged subventricular zone (SVZ) suffers an infiltration of T cells, which affects neural stem cell activity in mice. Whether this occurs in human neurogenic niches or to which extent T‐cell infiltration is also taking place in neurodegenerative diseases remains unknown. In this work, we studied the presence of T cells in both human neurogenic niches in young and old individuals. There was a significant increase in the number of CD3+ and CD8+ T cells in the SVZ of elderly individuals, which was not detected in the dentate gyrus. Moreover, we also found CD3+ and CD8+ T cells in the SVZ of individuals with neurodegenerative diseases. However, T‐cell count was similar when compared non‐neuropathological elderly with disease diagnosed patients. Our study reveals the infiltration of T cells in old human brains, particularly in the SVZ under non‐pathological conditions and also in neurodegenerative contexts. 相似文献
It has been reported that the over-stimulation of N-methyl-d-aspartate receptor (NR) modulates glutamate postsynaptic neurotransmission by generating long lasting Ca2+ channel openings. In the present study, we investigated ischemia-induced change in NR1 immunoreactivity and level in the
main olfactory bulb (MOB) after 5 min of transient forebrain ischemia in gerbils. NR1 immunoreactivity in the sham-operated
group was shown mainly in tufted cells of the external plexiform and in mitral cells of the mitral cell layer. NR1 immunoreactivity
in these neurons was increased with time and was very strong 15 days after ischemia/reperfusion. At that time, NR1 protein
level in the MOB was also highest. Thereafter, NR1 immunoreactivity and protein level in the MOB were decreased with time
after ischemia/reperfusion. Thus, NR1 in tufted and mitral cells in the gerbil MOB is changed after transient forebrain ischemia.
This suggests that mitral and tufted cells may be the principal neurons in the MOB affected in receiving inputs and sending
projections to the olfactory area after transient ischemia.
Y. Her and K.-Y. Yoo contributed equally to this article. 相似文献
In recent years, Disrupted-In-Schizophrenia 1 (DISC1) has emerged as one of the most promising candidate genes whose disruption confers an increased risk for schizophrenia. Cell biology studies have implicated DISC1 in key neurodevelopmental processes including neurite outgrowth and neuronal migration. In situ hybridization analysis has revealed that Disc1 is expressed in the hypothalamus, olfactory bulbs, the developing cerebral cortex and the hippocampus. The hippocampus is of particular interest because abnormalities in hippocampal volume and function have been consistently reported in schizophrenics. Moreover, DISC1 mutations have been associated with abnormal activation of the hippocampus in humans. Given the involvement of the hippocampus in the pathophysiology of schizophrenia, there is an intriguing possibility that disruption of DISC1 may increase schizophrenia susceptibility by altering the normal development and function of the hippocampus. In order to contribute to our understanding of DISC1's role in the hippocampus, we have performed a detailed analysis of the Disc1 expression pattern in the mouse hippocampus throughout development. We report that Disc1 is expressed throughout the hippocampus during embryonic development, with expression becoming increasingly specialized in Ammon's horn and dentate gyrus granule cells within the first postnatal week. This expression pattern remains consistent into adulthood, with a noted decrease in Disc1 expression in the adult CA1. Disc1 is also expressed in proliferating cells in the adult subgranular zone, as well as in a subset of GABAergic interneurons. Our results are the first report of a detailed immunohistochemical analysis of the ontogeny of Disc1 expression within the hippocampus. 相似文献
We investigated the role of miR-522-3p in thymoma-associated myasthenia gravis (TAMG), and the mechanism of action in T cells. The miR-522-3p expression in normal serum, non-thymoma MG patient serum and TAMG patient serum and tissues was detected by quantitative real-time PCR (qRT-PCR), respectively. We assessed miR-522-3p expression in Jurkat cells and human CD4+ T cells after activation by anti-CD3 and anti-CD28 using qRT-PCR. The viability, proliferation, cycle distribution and the levels of CD25, CD69, interleukin-2 (IL-2) and IL-10 in transfected Jurkat cells were detected by Cell counting kit-8, 5-ethynyl-2′-deoxyuridine (EdU), flow cytometry, qRT-PCR, respectively. Targeting relationships of miR-522-3p and SLC31A1 were predicted and validated by bioinformatics analysis and dual-luciferase reporter. The viability, proliferation, cycle distribution and the levels of SLC31A1, CD25, CD69, IL-2 and IL-10 in transfected Jurkat cells were detected by above methods and western blot. The miR-522-3p expression was declined in TAMG and activated T cells. MiR-522-3p inhibitor promoted cell viability, EdU positive cells, cycle progression, and the level of CD25, CD69, IL-2 and IL-10 in Jurkat cells, while the effect of miR-522-3p mimic was the opposite. SLC31A1 was targeted by miR-522-3p, and miR-522-3p inhibited SLC31A1 expression. Overexpressed SLC31A1 reversed the inhibitory effects of miR-522-3p mimic on cell viability, EdU positive cell, cycle progression, and the levels of IL-2 and IL-10 in transfected Jurkat cells. MiR-522-3p expression was down-regulated in TAMG, and miR-522-3p inhibited proliferation and activation by regulating SLC31A1 expression in T cells.