In newborn rats the levels of nerve growth factor (NGF) mRNA (mRNANGF) and NGF receptor (mRNA(rec)) in sciatic were 10 120 times higher, respectively, than adult animals. mRNA(rec) decreased steadily from birth, approaching by third postnatal week, whereas mRNANGF only after first although also reaching week. Transection resulted a marked biphasic increase with time. On proximal side cut, this was confined to area immediately adjacent cut; peripherally, similar present all segments. markedly...

In the central nervous system brain-derived neurotrophic factor (BDNF) and nerve growth (NGF) are predominantly located in neurons. Here we demonstrate that balance between activity of glutamatergic gamma-aminobutyric acid (GABA)ergic systems controls physiological levels BDNF NGF mRNAs hippocampal neurons vitro vivo. The blockade glutamate receptors and/or stimulation GABAergic reduces hippocampus protein septum. reduction septum reflects diminished availability projection field...

Specific sensory input has profound transient and long-lasting effects on the function of corresponding cortical areas both during development in adulthood. To study whether neurotrophic factors might play a role such processes, we investigated light nerve growth factor brain-derived (BDNF) mRNA levels rat visual cortex. Keeping adult rats dark or preventing normal activity retinal ganglion cells by intraocular injection tetrodotoxin significantly decreased BDNF cortex but not other areas....

Transforming growth factor-beta 1 (TGF-beta 1) has been shown to up-regulate the synthesis of nerve factor (NGF) in cultured rat astrocytes and neonatal brain vivo (Lindholm, D., B. Hengerer, F. Zafra, H. Thoenen. 1990. NeuroReport. 1:9-12). Here we show that mRNA encoding TGF-beta increased cerebral cortex after a penetrating injury. The level NGF is also transiently trauma, whereas brain-derived neurotrophic remained unchanged. In situ hybridization experiments showed strong expression 4 d...

Brain-derived neurotrophic factor (BDNF) and NGF are both expressed by neurons in the hippocampus. In previous studies, it has been demonstrated that BDNF mRNA levels regulated neuronal activity. Upregulation is predominantly glutamate (NMDA non-NMDA receptors); downregulation, GABA system (Zafra et al., 1990, 1991). cultures of rat hippocampus, potassium depolarization kainic acid-mediated increases were eliminated a dose-dependent manner calcium channel blocker nifedipine. Conversely,...

Abstract In order to obtain information on the physiological regulation of NGF‐synthesis in central nervous system (CNS) we investigated effects a series growth factors (known be present CNS) cultures purified rat astrocytes and compared these with those observed after intraventricular injection same molecules. After preliminary experiments had shown that 10% fetal calf serum (FCS) produced marked increase NGF‐mRNA levels (but neither microglia nor oligodendrocytes) as demonstrated by...

Elevated brain glutamate with activation of neuronal receptors accompanies neurological disorders, such as epilepsy and trauma. However, the mechanisms by which excitotoxicity triggers injury are not fully understood. We have studied receptor agonist kainic acid (KA) inducing seizures excitotoxic cell death. KA caused disintegration endoplasmic reticulum (ER) membrane in hippocampal neurons ER stress proteins Bip, Chop, caspase-12. Salubrinal, inhibiting eIF2α (eukaryotic translation...

The neuroprotective action of brain-derived neurotrophic factor (BDNF) was evaluated in a rat model transient forebrain ischemia. A continuous intraventricular infusion BDNF for 7 days starting immediately before the onset ischemia significantly increased number pyramidal cells vulnerable CA1 sector hippocampus. In situ hybridization experiments suggest neuroprotection to be mediated via trkB – receptors data indicate therapeutic potential treatment cerebral

Lesion of the sciatic nerve caused a rapid increase in c-fos and c-jun mRNA that was followed about 2 hr later by an growth factor (NGF) mRNA. To evaluate whether initial is causally related to subsequent NGF mRNA, we performed experiments with fibroblasts transgenic mice carrying exogenous gene under control metallothionein promoter. In primary cultures these fibroblasts, CdCl2 evoked immediately endogenous slight delay C3H mice, had no effect on levels protooncogenes or NGF. Additional...

We have investigated the expression of mRNAs for brain-derived neurotrophic factor (BDNF), nerve growth (NGF), neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) in hippocampus before after induction long term potentiation (LTP) synaptic transmission dentate gyrus through stimulation perforant path (PP). A unilateral PP produced a bilateral increase mRNA both BDNF NGF granular neurones but not other hippocampus. The was bilaterally decreased by LTP that NT-4 remained at basal level. These...

Abstract In the rat hippocampus, nerve growth factor (NGF) and brain‐derived neurotrophic (BDNF) are synthesized by neurons in an activity‐dependent manner. Glutamate receptor activation increases whereas GABAergic stimulation decreases NGF BDNF mRNA levels. Here we demonstrate that protein up‐regulated hippocampus of muscarinic receptors. Conversely, enhance release acetylcholine (ACh) from hippocampal synaptosomes containing endings septal cholinergic neurons. also rapidly high‐affinity...

Abstract We have studied the effects of different neurotrophins on survival and proliferation rat cerebellar granule cells in culture. These neurons express trkB trkC, putative neuronal receptors for brain‐derived neurotrophic factor (BDNF) neurotrophin‐3 (NT‐3) respectively. Binding studies using iodinated BDNF NT‐3 demonstrated that both bind to with a similar affinity ˜ 2x10 ‐9 M. The number per cell was surprisingly high, ∼30x10 ‐4 2x 10 5 NT‐3, Both elevated c‐fos mRNA neurons, but only...

In situ hybridization on sections from the adult rat peripheral and central nervous systems demonstrated that trkB mRNA was expressed not only by neurons but also cells in system white matter as well Schwann sciatic nerve. with an oligonucleotide complementary to tyrosine kinase domain could demonstrate neurons, indicating expression of truncated receptors lacking glial cells. RNA blot analysis performed separately cultured study which cell types express mRNA. Several transcripts encoding...

The lymphokine interleukin 1 (IL-1) rapidly increases the levels of mRNA encoding nerve growth factor (NGF) in primary cultures fibroblasts isolated from adult rat sciatic nerves. effect IL-1 on NGF-mRNA was not inhibited by cycloheximide, which itself increased NGF-mRNA. From blocking ability actinomycin D, it deduced that action depends continuous RNA synthesis and half-life is about 90 min. Nuclear run-on studies showed that, although enhances low basic transcription, main results...

gamma-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in adult mammalian central nervous system. However, GABA depolarizes immature rat hippocampal neurons and increases intracellular Ca2+ ([Ca2+]i). Here we show, that GABAA receptor agonist muscimol induce c-Fos immunoreactivity increase BDNF mRNA expression embryonic cultured for 5 days. In contrast, after 3 weeks culture, failed to c-fos expression. Fura-2 fluorescence microscopy revealed produces a...

We have found a regional distribution of IL 1 beta mRNA and activity in the normal adult rat brain, which reveals at least partially colocalization with nerve growth factor (NGF). The predominantly neuronal signal patterns were over granule cells dentate gyrus, pyramidal hippocampus, cerebellum, periglomerular olfactory bulb, dispersed ventromedial hypothalamus frontal cortex. In these areas also highest levels observed. striatum septum much lower (shown for striatum), most likely...

In previous experiments it has been demonstrated that the synthesis of BDNF (brain-derived neurotrophic factor) and NGF in neurons hippocampus is regulated by neuronal activity. The glutamate system predominantly responsible for upregulation GABAergic downregulation both vitro vivo (Zafra et al., 1990, 1991). aim present study to examine extent which cholinergic also involved regulation mRNA whether regulatory contribution changes during development. Partial transection fimbria fornix bundle...