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21.
Deumens R Koopmans GC Honig WM Maquet V Jérôme R Steinbusch HW Joosten EA 《Neuroscience letters》2006,400(3):208-212
Regrowth of injured axons across rather small spinal cord lesion gaps and subsequent functional recovery has been obtained after many interventions. Long-distance regeneration of injured axons across clinically relevant large spinal lesion gaps is relatively unexplored. Here, we aimed at stimulating long-distance regrowth of the injured corticospinal (CS) tract. During development, an oriented framework of immature astrocytes is important for correct CS axon outgrowth. Furthermore, a continuous growth promoting substrate may be needed to maintain a CS axon regrowth response across relatively large spinal lesion gaps. Hence, we acutely transplanted poly(d,l)-lactide matrices, which after seeded with immature astrocytes render aligned astrocyte-biomatrix complexes (R. Deumens, et al. Alignment of glial cells stimulates directional neurite growth of CNS neurons in vitro. Neuroscience 125 (3) (2004) 591–604), into 2-mm long dorsal hemisection lesion gaps. In order to create a growth promoting continuum, astrocyte suspensions were also injected rostral and caudal to the lesion gap. During 2 months, locomotion was continuously monitored. Histological analysis showed that astrocytes injected into host spinal tissue survived, but did not migrate. None of the astrocytes on the biomatrices survived within the lesion gap. BDA-labeled CS axons did not penetrate the graft. However, directly rostral to the lesion gap, 120.9 ± 38.5% of the BDA-labeled CS axons were present in contrast to 12.8 ± 3.9% in untreated control animals. The observed anatomical changes were not accompanied by locomotor improvements as analyzed with the BBB and CatWalk. We conclude that although multifactorial strategies may be needed to stimulate long-distance CS axon regrowth, future studies should focus on enhancing the viability of cell/biomatrix complexes within large spinal lesion gaps. 相似文献
22.
Age-related loss of synaptophysin immunoreactive presynaptic boutons within the hippocampus of APP751SL, PS1M146L, and APP751SL/PS1M146L transgenic mice 总被引:6,自引:0,他引:6 下载免费PDF全文
Rutten BP Van der Kolk NM Schafer S van Zandvoort MA Bayer TA Steinbusch HW Schmitz C 《The American journal of pathology》2005,167(1):161-173
Neuron and synapse loss are important features of the neuropathology of Alzheimer's disease (AD). Recently, we observed substantial age-related hippocampal neuron loss in APP751SL/PS1M146L transgenic mice but not in PS1M146L mice. Here, we investigated APP751SL mice, PS1M146L mice, and APP751SL/PS1M146L mice for age-related alterations in synaptic integrity within hippocampal stratum moleculare of the dentate gyrus (SM), stratum lucidum of area CA3 (SL), and stratum radiatum of area CA1-2 (SR) by analyzing densities and numbers of synaptophysin-immunoreactive presynaptic boutons (SIPBs). Wild-type mice, APP751SL mice and PS1M146L mice showed similar amounts of age-related SIPB loss within SM, and no SIPB loss within SL. Both APP751SL mice and PS1M146L mice showed age-related SIPB loss within SR. Importantly, APP751SL/PS1M146L) mice displayed the severest age-related SIPB loss within SM, SL, and SR, even in regions free of extracellular Abeta deposits. Together, these mouse models offer a unique framework to study the impact of several molecular and cellular events caused by mutant APP and/or mutant PS1 on age-related alterations in synaptic integrity. The observation of age-related SIPB loss within SR of PS1M146L mice supports a role of mutant PS1 in neurodegeneration apart from its contribution to alterations in Abeta generation. 相似文献
23.
Interchromosomal duplications of the adrenoleukodystrophy locus: a phenomenon of pericentromeric plasticity 总被引:13,自引:5,他引:13
Eichler EE; Budarf ML; Rocchi M; Deaven LL; Doggett NA; Baldini A; Nelson DL; Mohrenweiser HW 《Human molecular genetics》1997,6(7):991-1002
A 9.7 kb segment encompassing exons 7-10 of the adrenoleukodystrophy (ALD)
locus of the X chromosome has duplicated to specific locations near the
pericentromeric regions of human chromosomes 2p11,10p11, 16p11 and 22q11.
Comparative sequence analysis reveals 92-96% nucleotide identity,
indicating that the autosomal ALD paralogs arose relatively recently during
the course of higher primate evolution (5-10 million years ago). Analysis
of sequences flanking the duplication region identifies the presence of an
unusual GCTTTTTGC repeat which may be a sequence-specific integration site
for the process of pericentromeric- directed transposition. The breakpoint
sequence and phylogenetic analysis predict a two-step transposition model,
in which a duplication from Xq28 to pericentromeric 2p11 occurred once,
followed by a rapid distribution of a larger duplicon cassette among the
pericentromeric regions. In addition to facilitating more effective
mutation detection among ALD patients, these findings provide further
insight into the molecular basis underlying a pericentromeric-directed
mechanism for non- homologous interchromosomal exchange.
相似文献
24.
Delivery of normal twins following the intracytoplasmic injection of spermatozoa from a patient with 47,XXY Klinefelter's syndrome 总被引:4,自引:9,他引:4
Bourne H; Stern K; Clarke G; Pertile M; Speirs A; Baker HW 《Human reproduction (Oxford, England)》1997,12(11):2447-2450
Klinefelter's syndrome is a disorder of gonadal development and typically
reveals a 47,XXY karyotype although mosaic forms also occur. Azoospermia is
a common feature, but severe oligozoospermia and fertility have been
reported. In this study, we have used intracytoplasmic sperm injection
(ICSI) to achieve a live twin birth using spermatozoa from a 47,XXY man who
has occasional spermatozoa present in the ejaculate. Spermatozoa were
obtained from multiple ejaculates and frozen prior to commencing IVF
treatment. Nine good quality embryos developed from the injection of 13
oocytes. All nine embryos were frozen. The initial transfer of two
frozen-thawed embryos was unsuccessful. In the following cycle, the
transfer of two additional frozen-thawed embryos resulted in the delivery
of normal, healthy male and female twins. Five embryos remain frozen. It
has generally been thought that the germ cells of 47,XXY men are unable to
proceed through meiosis. Any spermatozoa produced have been assumed to come
from a normal germ cell and therefore likely to have a normal karyotype.
However, recent evidence suggests that meiosis of 47,XXY germ cells may be
possible. Whether spermatozoa in these men arise from meiosis of 47,XXY
germ cells, or from germ cells which have attained a normal karyotype by
loss of an X chromosome, is unclear. Any risks in using spermatozoa from
these patients have not yet been established. Patients need to be advised
accordingly, and preimplantation or prenatal diagnosis should be
considered. A cautious approach to the treatment of these patients is
therefore warranted.
相似文献
25.
Clarke GN; Bourne H; Hill P; Johnston WI; Speirs A; McBain JC; Baker HW 《Human reproduction (Oxford, England)》1997,12(4):722-726
Donor insemination (DI) using cryopreserved semen commenced at The Royal
Women's Hospital in 1976. Over the next 15 years we performed 5953
treatment cycles to achieve 816 pregnancies (13.7% per cycle) and 706 live
births. In-vitro fertilization (IVF) using donor spermatozoa commenced in
1986. Over the next 5 years we performed 303 treatment cycles for 185
couples. Including subsequent transfer of cryopreserved embryos, a total of
33% of couples achieved a successful pregnancy by IVF. Statistical analysis
indicated that, for DI pregnancies, the most important semen variable was
the percentage post-thaw motility, whilst for normal fertilization in IVF
it was the pre-freeze motility. These results may be explained by the
compensatory effects of post-thaw processing of spermatozoa for IVF, but
not for DI in our clinic.
相似文献
26.
Börje Bjelke Menek Goldstein Barbro Tinner Cecilia Andersson Susan R. Sesack Harry W.M. Steinbusch Jow Y. Lew Xi He Stan Watson Björn Tengroth Kjell Fuxe 《Journal of chemical neuroanatomy》1996,12(1):37-50
The study was designed to determine whether dopaminergic neurotransmission in the retina can operate via volume transmission. In double immunolabelling experiments, a mismatch as well as a match was demonstrated in the rat retina between tyrosine hydroxylase (TH) and dopamine (DA) immunoreactive (ir) terminals and cell bodies and dopamine D2 receptor-like ir cell bodies and processes. The match regions were located in the inner nuclear and plexiform layers (D2 ir cell bodies plus processes). The mismatch regions were located in the ganglion cell layer, the outer plexiform layer, and the outer segment of the photoreceptor layer, where very few TH ir terminals can be found in relation to the D2 like ir processes. In similar experiments analyzing D1 receptor like ir processes versus TH ir nerve terminals, mainly a mismatch in their distribution could be demonstrated, with the D1 like ir processes present in the outer plexiform layer and the outer segment where a mismatch in D2 like receptors also exists. The demonstration of a mismatch between the localization of the TH terminal plexus and the dopamine D2 and D1 receptor subtypes in the outer plexiform layer, the outer segment and the ganglion cell layer (only D2 immunoreactivity (IR)) suggests that dopamine, mainly from the inner plexiform layer, may reach the D2 and D1 mismatch receptors via diffusion in the extracellular space. After injecting dopamine into the corpus vitreum, dopamine diffuses through the retina, and strong catecholamine (CA) fluorescence appears in the entire inner plexiform layer and the entire outer plexiform layer, representing the match and mismatch DA receptor areas, respectively. The DA is probably bound to D1 and D2 receptors in both plexiform layers, since the DA receptor antagonist chlorpromazine fully blocks the appearance of the DA fluorescence, while only a partial blockade is found after haloperidol treatment which mainly blocks D2 receptors. These results indicate that the amacrine and/or interplexiform DA cells, with sparse branches in the outer plexiform layer, can operate via volume transmission in the rat retina to influence the outer plexiform layer and the outer segment, as well as other layers of the rat retina such as the ganglion cell layer. 相似文献
27.
Loidl CF Gavilanes AW Van Dijk EH Vreuls W Blokland A Vles JS Steinbusch HW Blanco CE 《Physiology & behavior》2000,68(3):263-269
Previous studies in rats have demonstrated that perinatal asphyxia (PA) produces long-term morphological alterations, particularly affecting hippocampus. neostriatum, and cerebral cortex. These changes were prevented by applying hypothermia during the asphyctic insult. Because these cerebral areas are involved in cognitive and motor functions, the aim of the present study was to determine whether periods of PA during normothermia or hypothermia produces long-term behavioral impairments in rats of both sexes. The cognitive and motor functions were studied using the spatial Morris water maze (MWM) task at 1.5 months, and the open field at 5 months, respectively. The present study revealed that female rats had a higher survival rate than males after PA in normothermic conditions (p < 0.014). and that hypothermia drastically prolonged the time of survival in both sexes (p < 0.001). There were no differences in learning and memory functions between groups or male and female rats when tested with MWM. Rats subjected to hypothermia treatment did not show differences in the MWM compared to controls. A lower locomotor activity in the open field test was only observed in male rats that suffered 15 and 20 min of PA in normothermia (p < 0.05). Hypothermia treatment prevented this hypoactivity. PA in females, even if severe, did not affect the motor activity. The data of both behavioral tests showed differences between sexes, i.e., the female rats learned the MWM task slower, and were more active in the open field. This work lends further support for the hypothesis that hypothermia can prevent mortality as well as long-term sequelae induced by PA. 相似文献
28.
Vanhatalo S Parkkisenniemi U Steinbusch HW de Vente J Klinge E 《Journal of chemical neuroanatomy》2000,19(2):169-91
The distribution of immunoreactivity (IR) for the neuropeptide vasoactive intestinal polypeptide (VIP) and neuronal nitric oxide synthase (nNOS) in the bovine retractor penis muscle (RP) and penile artery (PA) was studied by using two different methods. The distribution of these immunoreactivities was also compared with that of the immunoreactivity for cyclic guanosine monophosphate (cGMP). In both tissues the nerve fibers and terminals immunoreactive for VIP had a distribution that was completely different from that of the nerve fibers and terminals immunoreactive for nNOS. This contrasts with the previous observations in penile smooth muscle of other species. In the RP, as well as in the PA, many of the VIP-IR fibers were also immunoreactive for neurofilaments (NF), whereas the nNOS-IR fibers were consistently devoid of NF-IR. Stimulation with sodium nitroprusside, a nitric oxide donor, considerably increased cGMP-IR in the smooth muscle cells in both RP and PA, and in several nerve fibers in PA. Many of these cGMP-IR nerve fibers exhibited nNOS-IR, whereas none of them was immunoreactive for VIP. Our results suggest that the degree of coexistence of VIP-IR and nNOS-IR in the nerve fibers and terminals innervating penile smooth muscle show wide species differences. They also suggest that the mechanisms by which VIP could be involved in neurogenic penile erection may vary between species. 相似文献
29.
Lemmens MA Sierksma AS Rutten BP Dennissen F Steinbusch HW Lucassen PJ Schmitz C 《Brain structure & function》2011,216(3):227-237
Alzheimer’s disease (AD) is a neurodegenerative disorder, characterized by amyloid plaque accumulation, intracellular tangles
and neuronal loss in selective brain regions. The frontal cortex, important for executive functioning, is one of the regions
that are affected. Here, we investigated the neurodegenerative effects of mutant human amyloid precursor protein (APP) and
presenilin 1 (PS1) on frontal cortex neurons in APP/PS1KI mice, a transgenic mouse model of AD, expressing two mutations in
the human APP, as well as two human PS1 mutations knocked-in into the mouse PS1 gene in a homozygous (ho) manner. Although
the hippocampus is significantly affected in these mice, very little is known about the effects of these mutations on selective
neuronal populations and plaque load in the frontal cortex. In this study, cytoarchitectural changes were characterized using
high precision design-based stereology to evaluate plaque load, total neuron numbers, as well as total numbers of parvalbumin-
(PV) and calretinin- (CR) immunoreactive (ir) neurons in the frontal cortex of 2- and 10-month-old APP/PS1KI mice. The frontal
cortex was divided into two subfields: layers II–IV and layers V–VI, the latter of which showed substantially more extracellular
amyloid-beta aggregates. We found a 34% neuron loss in layers V–VI in the frontal cortex of 10-month-old APP/PS1KI mice compared
to 2-month-old, while there was no change in PV- and CR-ir neurons in these mice. In addition, the plaque load in layers V–VI
of 10-month-old APP/PS1KI mice was only 11% and did not fully account for the extent of neuronal loss. Interestingly, an increase
was found in the total number of PV-ir neurons in all frontal cortical layers of single transgenic APP mice and in layers
II–IV of single transgenic PS1ho mice between 2 and 10 months of age. In conclusion, the APP/PS1KI mice provide novel insights
into the regional selective vulnerability in the frontal cortex during AD that, together with previous findings in the hippocampus,
are remarkably similar to the human situation. 相似文献
30.
Sarah Hescham Lee Wei Lim Ali Jahanshahi Harry W.M. Steinbusch Jos Prickaerts Arjan Blokland Yasin Temel 《Brain stimulation》2013,6(1):72-77
Deep brain stimulation (DBS) is currently being evaluated as a potential therapy in improving memory functions in Alzheimer’s disease. The target for DBS and the stimulation parameters to be used are unknown. Here, we implanted bilateral electrodes in the vicinity of the fornix, a key element of the memory circuitry, and applied DBS with different stimulation frequencies and amplitudes in an experimental model of dementia. Rats received scopolamine, a muscarinic acetylcholine receptor antagonist, to mimic memory impairment. Rats were then tested in the object location task with the following conditions: (i) with attachment of stimulation cable (off stimulation), and (ii) with DBS at various amplitudes (50 μA, 100 μA and 200 μA), 100 μs pulse width and 100 Hz or 10 Hz stimulation frequency. DBS reversed the memory impairing effects of scopolamine when compared to sham rats. We found that the fornix is not sensitive to the frequency of stimulation, but rather to current levels. With the most optimal stimulation parameter, we found no side-effects on anxiety levels and general motor activity. These findings identify the fornix as a key region in controlling spatial memory functions. DBS of this region, using tailored stimulation parameters, has the potential to improve memory functions in conditions characterised by memory impairment. 相似文献