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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Optic nerve transection in adult rats results in the death of approximately 50% of the axotomized retinal ganglion cells (RGCs) by 1 week and nearly 90% by 2 weeks after injury. The capacity of brain-derived neurotrophic factor (BDNF) to prevent this early, severe loss of RGCs was investigated in vivo by intravitreal injections of BDNF [5 micrograms in 5 microliters of bovine serum albumin/phosphate-buffered saline (BSA/PBS)] or vehicle (5 microliters of BSA/PBS). Using quantitative anatomical techniques, we show that (i) all RGCs survived 1 week after a single injection of BDNF at the time of axotomy. (ii) RGC densities decreased in the BDNF-treated retinas by 2 weeks but remained significantly greater than in the untreated controls. (iii) An enhanced RGC survival was obtained with single injections of BDNF from 6 days before to 5 days after axotomy. (iv) Repeated injections resulted in greater numbers of surviving RGCs, an effect that declined to undetectable levels by 6 weeks. (v) There were indications for an endogenous local source of trophic support whose expression was triggered by ocular injury, particularly to the anterior part of the eye. (vi) With multiple BDNF injections, there was profuse axonal sprouting around the optic disc. This remarkable intraretinal growth was not, however, reflected in increased RGC innervation of the peripheral nerve grafts, which are known to facilitate regeneration when used as optic nerve substitutes.
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PMID:Effects of ocular injury and administration of brain-derived neurotrophic factor on survival and regrowth of axotomized retinal ganglion cells. 812 57

A pathology of brain serotonergic (5-HT) systems has been found in psychiatric disturbances, normal aging and in neurodegenerative disorders including Alzheimer's and Parkinson's disease. Despite the clinical importance of 5-HT, little is known about the endogenous factors that have neurotrophic influences upon 5-HT neurons. The present study examined whether chronic pain parenchymal administration of the neurotrophins brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) or NGF could prevent the severe degenerative loss of serotonergic axons normally caused by the selective 5-HT neurotoxin p-chloroamphetamine (PCA). The neurotrophins (5-12 micrograms/d) or the control substances (cytochrome c or PBS vehicle) were continuously infused into the rat frontoparietal cortex using an osmotic minipump. One week later, rats were subcutaneously administered PCA (10 mg/kg) or vehicle, and the 5-HT innervation was evaluated after two more weeks of neurotrophin infusion. As revealed with 5-HT immunocytochemistry, BDNF infusions into the neocortex of intact (non-PCA-lesioned) rats caused a substantial increase in 5-HT axon density in a 3 mm diameter region surrounding the cannula tip. In PCA-lesioned rats, intracortical infusions of BDNF completely prevented the severe neurotoxin-induced loss of 5-HT axons near the infusion cannula. In contrast, cortical infusions of vehicle or the control protein cytochrome c did not alter the density of serotonergic axons in intact animals, nor did control infusions prevent the loss of 5-HT axons in PCA-treated rats. NT-3 caused only a modest sparing of the 5-HT innervation in PCA-treated rats, and NGF failed to prevent the loss of 5-HT axon density. The immunocytochemical data were supported by neurochemical evaluations which showed that BDNF attenuated the PCA-induced loss of 5-HT and 5-HIAA contents and 3H-5-HT uptake near the infusion cannula. Thus, BDNF can promote the sprouting of mature, uninjured serotonergic axons and dramatically enhance the survival or sprouting of 5-HT axons normally damaged by the serotonergic neurotoxin PCA.
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PMID:Brain-derived neurotrophic factor promotes the survival and sprouting of serotonergic axons in rat brain. 861 31

A rapid and reproducible spinal motor neuron death occurs after sciatic nerve transection in neonatal rats. This neuronal death could be due to lack of retrogradely transported target derived neurotrophic factors, such as ciliary neurotrophic factor, brain-derived neurotrophic factor, leukemia inhibitory factor and glial cell line-derived neurotrophic factor. Another hypothesis suggests that glutamate and its receptors has been implicated as possible mechanism for motor neuron death. In order to investigate the effect of N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists on axotomy-induced cell death in the spinal motor neurons of neonatal rats, we have studied neuroprotective effects of these receptor antagonists. Newborn rats were anesthetized with hypothermia. Sciatic nerve was transected near the obturator tendon in the left thigh. Animals were then treated daily with MK-801, APV, and CNQX for 14 days with intraperitoneal injections. Control animals received PBS in the same fashion. After the treatment, the number of spinal motor neurons in the L4-6 was counted. MK-801 and APV did not show any significant neuroprotective effect. By contrast, the number of surviving motor neurons was greater in animals that were treated with 1.0, 2.0 and 4.0 mg/kg of CNQX. This neuroprotective effect was not dose-related. We demonstrate that neuroprotective effect of CNQX on axotomized motor neurons, raises a possibility that such a agent may have therapeutic potential in motor neuronopathy and amyotrophic lateral sclerosis.
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PMID:CNQX prevents spinal motor neuron death following sciatic nerve transection in newborn rats. 874 38

We have previously demonstrated that the most rostral part of the subventricular zone (SVZ) is a source of neuronal progenitor cells whose progeny are destined to become interneurons of the olfactory bulb. To determine whether the number of newly generated neurons in the adult olfactory bulb could be increased by the administration of an exogenous factor, brain-derived neurotrophic factor (BDNF) was infused for 12 days into the right lateral ventricle of adult rat brains. The production of new cells was monitored by either the intraventricular infusion or intraperitoneal injection of the cell proliferation marker BrdU. In both experimental paradigms we observed significantly more BrdU-labeled cells in the olfactory bulbs on the BDNF-infused side than in the olfactory bulb of PBS-infused animals. Analysis of the BDNF-infused brains of animals injected intraperitoneally with BrdU demonstrated a 100% increase in the number of BrdU-labeled cells in the bulb, the preponderance ( approximately 90%) of which were double-labeled with a neuron-specific antibody. These results demonstrate that the generation and/or survival of new neurons in the adult brain can be increased substantially by an exogenous factor. Furthermore, the SVZ, and in particular the rostral part, may constitute a reserve pool of progenitor cells available for neuronal replacement in the diseased or damaged brain.
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PMID:Intraventricular administration of BDNF increases the number of newly generated neurons in the adult olfactory bulb. 967 54

The present study tested the effects of in vivo administration of brain-derived neurotrophic factor (BDNF) and of its antibody (anti-BDNF) in a Morris Water Maze (MWM) task. Adult male rats were trained for three days in a MWM. At the end of the last training trial, subjects were injected intracerebroventricularly with one of the following: (i) BDNF (24 microg); (ii) anti-BDNF (25 microg); or (iii) vehicle (PBS, injection volume 10 microl). On day 5, subjects were tested for memory retention, pain sensitivity and locomotor behaviour. No differences emerged in the MWM as a function of treatment, even with a reduced number of acquisition trials. Nonetheless, BDNF affected both pain threshold in the hot-plate test, as well as exploratory behaviour in the open field test.
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PMID:Intracerebroventricular administration of brain-derived neurotrophic factor in adult rats affects analgesia and spontaneous behaviour but not memory retention in a Morris Water Maze task. 1086 31

In androgen-sensitive motoneurons of the spinal nucleus of the bulbocavernosus (SNB), we investigated the interaction of BDNF (brain-derived neurotrophic factor) and testosterone to understand whether each factor gates the ability of the other to regulate androgen receptor expression and soma size, and whether each factor requires the presence of the other for its action. We axotomized SNB motoneurons and applied BDNF or PBS (phosphate-buffered saline) to the cut ends of the axons in rats that were castrated and treated with either testosterone or placebo. Control groups were either not castrated or not axotomized, or had intact SNB axons and were castrated and treated with testosterone or placebo. We found that testosterone determined the expression of nuclear androgen receptor, and this effect was enhanced by both BDNF and contact with the target muscles. The effect of BDNF on androgen receptor expression was seen only when testosterone was present. In the regulation of soma size, BDNF dominated. The application of BDNF completely compensated for the loss of testosterone in castrated males so that the testosterone effect on soma size was seen only in intact SNB motoneurons and in axotomized motoneurons treated with PBS. Moreover, testosterone increased androgen receptor and soma size in axotomized SNB motoneurons, indicating that testosterone can act on sites other than the target muscles of the SNB to regulate each of these. These results indicate that the regulation of androgen receptor by testosterone does not require BDNF, but the regulation of androgen receptor by BDNF does require testosterone. The regulation of soma size by BDNF does not require high expression of nuclear androgen receptor.
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PMID:Interaction of BDNF and testosterone in the regulation of adult perineal motoneurons. 1094 84

The results of several studies have contributed to the hypothesis that BDNF promotes seizure activity, particularly in adult hippocampus. To test this hypothesis, BDNF, vehicle (phosphate-buffered saline, PBS), or albumin was infused directly into the hippocampus for 2 weeks using osmotic minipumps. Rats were examined behaviorally, electrophysiologically, and anatomically. An additional group was tested for sensitivity to the convulsant pilocarpine. Spontaneous behavioral seizures were observed in BDNF-infused rats (8/32; 25%) but not in controls (0/20; 0%). In a subset of six animals (three BDNF, three albumin), blind electrophysiological analysis of scalp recordings contralateral to the infused hippocampus demonstrated abnormalities in all BDNF rats; but not controls. Neuronal loss in BDNF-treated rats was not detected relative to PBS- or albumin-treated animals, but immunocytochemical markers showed a pattern of expression in BDNF-treated rats that was similar to rats with experimentally induced seizures. Thus, BDNF-infused rats had increased expression of NPY in hilar neurons of the dentate gyrus relative to control rats. NPY and BDNF expression was increased in the mossy fiber axons of dentate gyrus granule cells relative to controls. The increase in NPY and BDNF expression in BDNF-treated rats was bilateral and occurred throughout the septotemporal axis of the hippocampus. Mossy fiber sprouting occurred in five BDNF-treated rats but no controls. In another group of infused rats that was tested for seizure sensitivity to the convulsant pilocarpine, BDNF-infused rats had a shorter latency to status epilepticus than PBS-infused rats. In addition, the progression from normal behavior to severe seizures was faster in BDNF-treated rats. These data support the hypothesis that intrahippocampal BDNF infusion can facilitate, and potentially initiate, seizure activity in adult hippocampus.
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PMID:Spontaneous limbic seizures after intrahippocampal infusion of brain-derived neurotrophic factor. 1192 62

Neurotrophic factors regulate a variety of cellular processes, including neuronal survival during development and after injury. For instance, brain-derived neurotrophic factor (BDNF) can prevent the death of dopaminergic substantia nigra neurons in rats. Most neurotrophic factor receptors, such as TrkB for BDNF, are tyrosine kinases whose signaling is terminated by protein tyrosine phosphatases (PTPs). We tested the idea that inhibition of PTPs, and thus potentially enhancement of the efficiency of endogenous trophic factors and their receptors, would lead to increased neuronal survival. After a 2-week infusion of the small PTP inhibitor molecule peroxovanadium (pVa, pervanadate) close to the substantia nigra of adult rats, up to 66% of axotomized substantia nigra neurons had survived, compared to only 33% in control rats infused with PBS. PVa most likely affected TrkB and/or downstream signaling molecules, as ineffective doses of BDNF and pVa had a synergistic effect when given simultaneously, rescuing 82% of the neurons. PVa stimulated tyrosine hydroxylase (TH) expression in the noninjured substantia nigra but did not prevent axotomy-induced loss of TH. These results raise the possibility that PTP inhibition can prevent neuronal death by enhancing neurotrophic factor signaling pathways in the adult mammalian nervous system, identifies an important role for PTPs in neuronal functioning, and points to a novel small molecule treatment approach for neurologic disorders
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PMID:Tyrosine phosphatase inhibition enhances neurotrophin potency and rescues nigrostriatal neurons in adult rats. 1250 84

This study was designed to examine the effects of bone marrow stromal cells (MSCs) cultured in vitro with or without neurotrophic factors transplanted into adult male Wistar rats after traumatic brain injury (TBI). MSCs harvested from donor Wistar rats were cultured with either the culture medium containing brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) or the same culture media without these factors. Control and experimental animals were then traumatized by a controlled cortical impact. One day after the impact, either the placebo or the washed MSCs (1 x 10(6)) cultured with or without NGF and BDNF were transplanted adjacent to the site of injury. In addition, a nontreated group of rats was employed. Motor function of the animals was evaluated by the Rotarod test both before and after the injury. All animals were sacrificed 8 days after TBI, and the brain sections were stained by H&E as well as for immunohistochemistry. MSCs survived and migrated toward the injury site. The group treated with MSCs cultured with BDNF and NGF had a significantly higher number of engrafted cells than the group treated with MSCs cultured without BDNF and NGF (6.3 x 10(4) +/- 4250 compared to 4.1 x 10(4) +/- 3684; p < 0.05). In both groups, some transplanted MSCs showed positive staining for astrocytic (GFAP) and neuronal markers (Neu N and MAP-2). The groups treated with MSCs had better motor function than the groups receiving no treatment or receiving the placebo (PBS; p < 0.05); however, the improvement reached statistical significance only in the group treated with MSCs cultured with neurotrophic factors. These data suggest that more robust motor function described in rats subjected to TBI and treated with intracerebral transplantation of MSCs was achieved by the use of MSCs cultured with neurotrophic factors.
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PMID:Intracerebral transplantation of marrow stromal cells cultured with neurotrophic factors promotes functional recovery in adult rats subjected to traumatic brain injury. 1254 61

We reported recently that overexpression of neurotrophin-3 (NT-3) by motoneurons in the spinal cord of rats will induce sprouting of corticospinal tract (CST) axons (Zhou et al. [2003] J. Neurosci. 23:1424-1431). We now report that overexpression of brain-derived neurotrophic factor (BDNF) or glial cell-derived neurotrophic factor (GDNF) in the rat sensorimotor cortex near the CST neuronal cell bodies together with overexpression of NT-3 in the lumbar spinal cord significantly increases axonal sprouting compared to that induced by NT-3 alone. Two weeks after unilaterally lesioning the CST at the level of the pyramids, we injected rats with saline or adenoviral vectors (Adv) carrying genes coding for BDNF (Adv.BDNF), GDNF (Adv.GDNF) or enhanced green fluorescent protein (Adv.EGFP) at six sites in the sensorimotor cortex, while delivering Adv.NT3 to motoneurons in each of these four groups on the lesioned side of the spinal cord by retrograde transport from the sciatic nerve. Four days later, biotinylated dextran amine (BDA) was injected into the sensorimotor cortex on the unlesioned side to mark CST axons in the spinal cord. Morphometric analysis of axonal sprouting 3 weeks after BDA injection showed that the number of CST axons crossing the midline in rats treated with Adv.BDNF or Adv.GDNF were 46% and 52% greater, respectively, than in rats treated with Adv.EGFP or PBS (P < 0.05). These data demonstrate that sustained local expression of neurotrophic factors in the sensorimotor cortex and spinal cord will promote increased axonal sprouting after spinal cord injury, providing a basis for continued development of neurotrophic factor therapy for central nervous system damage.
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PMID:Neurotrophic factors expressed in both cortex and spinal cord induce axonal plasticity after spinal cord injury. 1451 51


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