TrkB Receptor Expression Research Articles

Circadian variations in expression of the trkB receptor in adult rat hippocampus

The expression of brain-derived neurotrophic factor (BDNF) in the central nervous system (CNS) and the expression of its high-affinity trkB receptor on neuron surfaces are known to depend on neuron activity. The expression of BDNF (mRNA and protein) and trkB mRNA shows circadian oscillations in rat hippocampal homogenates. We investigated circadian variations in trkB expression in specific areas of the adult rat hippocampal formation by immunohistochemistry. In sets of two experiments performed in the spring, 39 2-month-old male Wistar rats were accustomed to a 12-h light–12-h dark cycle for 2 weeks. Three animals were then sacrificed every 4 h. Forty-micrometer-thick coronal sections of hippocampal formation were obtained and processed for trkB immunohistochemistry. Cell staining intensity was assessed by image analysis of different hippocampal areas on five sections per animal. Circadian rhythmicity was evaluated by the cosinor method. Statistically significant circadian variations in trkB expression were found in dentate gyrus, entorhinal cortex, and the CA3 and hilar regions of the hippocampus, with highest expression during the first half of the dark (activity) period. These findings suggest a relationship between trkB expression and the physiological neuronal activation of wakefulness. TrkB receptor expression in the hippocampal regions studied was continuous and changes were gradual over the 24-h cycle, suggesting that more complex regulatory mechanisms also intervened.

Cystitis-induced upregulation of tyrosine kinase (TrkA, TrkB) receptor expression and phosphorylation in rat micturition pathways.

This study examined tyrosine kinase receptor (Trk) expression and phosphorylation in lumbosacral dorsal root ganglia (DRG) after acute (8 or 48 hours) or chronic (10 days) cyclophosphamide (CYP)-induced cystitis. Increases in the number of TrkA-immunoreactive (IR) cell profiles were detected in the L1 and L6 DRG (four-fold; P < or = 0.01) and the S1 DRG (1.5-fold; P < or = 0.05) but not in the L2, L4, and L5 DRG with CYP-induced cystitis of acute and chronic duration compared with control rats. The number of TrkB-IR cell profiles increased in the L1 and L2 DRG (L1: 2.6-fold; L2: 1.4-fold; P < or = 0.05) and in the L6 and S1 DRG (L6: 2.2-fold; S1: 1.3-fold; P < or = 0.05) only after acute CYP treatment (8 hours). After CYP treatment, the percentage of bladder afferent cell profiles expressing TrkA-IR (approximately 50%; P < or = 0.05) increased in L1 and L6 DRG. The percentage of bladder afferent cell profiles expressing TrkB-IR (approximately 45%; P < or = 0.05) in L1, L2, L6, and S1 DRG also increased compared with control cell profiles. The increase in TrkA-IR in bladder afferent cells occurred 8 hours after CYP treatment and was maintained in L1 DRG with chronic (10 days) CYP-induced cystitis. However, the increase in bladder afferent cells expressing TrkB-IR only occurred at the most acute time point examined (8 hours). TrkA-IR and TrkB-IR cell profiles also demonstrated phosphorylated Trk-IR with acute and/or chronic CYP-induced cystitis. These results demonstrated that CYP-induced cystitis increases the expression and phosphorylation of Trk receptors in lumbosacral DRG. Expression of neurotrophic factors in the inflamed urinary bladder may contribute to this increased expression, and neurotrophic factor and Trk interactions may play unique roles in decreased urinary tract plasticity with CYP-induced cystitis.

Up-regulation of tyrosine kinase (Trka, Trkb) receptor expression and phosphorylation in lumbosacral dorsal root ganglia after chronic spinal cord (T8-T10) injury.

Previous studies have demonstrated changes in urinary bladder neurotrophic factors after bladder dysfunction. We have hypothesized that retrograde transport of neurotrophin(s) from the bladder to lumbosacral dorsal root ganglia (DRG) may play a role in bladder reflex reorganization after spinal cord injury (SCI). In this study, we determined whether the expression of tyrosine kinase receptors (TrkA, TrkB) is altered in lumbosacral DRG after SCI through immunofluorescence techniques. Complete transection of the spinal cord (T8-T10) was performed in female Wistar rats (120-150 g), and animals were studied 5-6 weeks after SCI. One week before killing, Fast Blue (FB) was injected into the bladder to label bladder afferent cells in the L1, L2, L6, and S1 DRG. After SCI, a significant increase in the number of TrkA-immunoreactive (IR) positive cells was detected in the L6-S1 DRG (L6: 1.9-fold, P < or = 0.01; S1: 1.7-fold, P < or = 0.05) and in the L1 DRG (3.0-fold; P < or = 0.01) but not in the L4-L5 DRG compared with spinal-intact (control) rats. After SCI, a significant increase in the number of TrkB-IR cells was also detected in the L6-S1 DRG (L6: 2.2-fold, P < or = 0.01; S1: 1.5-fold, P < or = 0.05) and in the L1-L2 DRG (L1: 1.5-fold, P < or = 0.01; L2: 1.3-fold, P < or = 0.05) but not in the L4-L5 DRG compared with control rats. After SCI, the percentage of FB-labeled cells expressing TrkA immunoreactivity (approximately 68%) or TrkB immunoreactivity (approximately 65%) in L1 and L6 DRG significantly (P < or = 0.01) increased compared with control (20-30%) DRG. After SCI, the percentage of TrkA-IR cells expressing phosphorylated (p)-Trk immunoreactivity significantly increased (1.5- to 2.3-fold increase) in the L1, L6, and S1 DRG. The percentage of TrkB-IR cells expressing p-Trk immunoreactivity after SCI also increased (1.3-fold increase) in the L1 and L6 DRG. These results demonstrate that (1) TrkA and TrkB immunoreactivity is increased in bladder afferent cells after SCI and (2) TrkA and TrkB receptors are phosphorylated in DRG after SCI. Neuroplasticity of lower urinary tract reflexes after SCI may be mediated by both nerve growth factor and brain-derived neurotrophic factor.

Ethanol-induced alterations of neurotrophin receptor expression on Purkinje cells in the neonatal rat cerebellum

Ethanol causes loss of Purkinje cells in the cerebellum during the early stages of differentiation and maturation by a presently unknown mechanism. Neuronal vulnerability in the cerebellum parallels the prominent temporal and anatomical gradients of development (i.e. early to late interlobular and posterior to anterior, respectively). Development of Purkinje cells is known to require binding of the neurotrophins, including brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3), to the tyrosine-kinase (Trk) receptors TrkB and TrkC, respectively. In addition, Purkinje cells are reported to experience a critical switch between BDNF dependence and NT3 dependence during the period of highest ethanol sensitivity between postnatal days (PN) 4–6. To test the hypothesis that ethanol alters neurotrophin signaling leading to Purkinje neuronal death, the immunohistochemical expression of TrkB and TrkC receptors on Purkinje cells of rat pups following a moderate dose of ethanol was determined at various times surrounding the period of postnatal ethanol vulnerability. Ethanol selectively decreased Purkinje cell expression of TrkB and TrkC receptors following exposures within the vulnerable period (PN4–6). These results suggest that ethanol may induce loss of Purkinje cells by alteration of neurotrophic regulation at this critical stage.

The Neuroprotective Agent Memantine Induces Brain-Derived Neurotrophic Factor and trkB Receptor Expression in Rat Brain

Memantine is a medium-affinity uncompetitive N-methyl-d-aspartate receptor antagonist and has been clinically used as a neuroprotective agent to treat Alzheimer's and Parkinson's diseases. We have examined the effect of memantine (ip 5–50 mg/kg; 4 h) on the expression of brain-derived neurotrophic factor (BDNF) and trkB receptor mRNAs in rat brain by in situ hybridization. Memantine at a clinically relevant dose markedly increased BDNF mRNA levels in the limbic cortex, and this effect was more widespread and pronounced at higher doses. Effects of memantine on BDNF mRNA were also reflected in changes in BDNF protein levels. Moreover, memantine induced isoforms of the BDNF receptor trkB. Taken together, these data suggest that the neuroprotective properties of memantine could be mediated by the increased endogenous production of BDNF in the brain. These findings may open up new possibilities of pharmacologically regulating the expression of neurotrophic factors in the brain.

Neurotrophin Effect On The SH‐SY5Y Human Neuroblastoma (HN) MODEL Of Cddp‐Induced Neurotoxicity

Neurotrophins (NGF, BDNF, NT‐3, NT‐4/5) have several pharmacological effects on adult neurons, and it has been proposed that they may play a role in sustaining the reparative mechanisms following peripheral nerve injuries. In this study we evaluated the effect of recombinant human (rh) neurotrophins (rhNGF, gifted by Boehringer Mannheim, Germany; rhBDNF and rhNT‐3 gifted by Amgen Co, USA) on cisplatin (CDDP)‐induced neurotoxicity in HN SH‐SY5Y neurotoxicity model. The cells were differentiated with RA 10 μM and exposed for 4 hours to 2.5 μg/ml CDDP with 50 ng/ml rhNGF, rhBDNF or rhNT‐3. Then the cells were maintained in DMEM, 10 μM RA and 50 ng/ml rhNGF, rhBDNF or rhNT‐3 and assessed for neurotoxicity 48, 72 and 96 hours after the first treatment with RA. Cells were considered “differentiated” when their neurite was longer than 50 μm. At each time point the neurite length was measured on at least 200 randomly selected cells/dish and the percentage of differentiated cells per culture was calculated. Exposure of RA‐differentiated SH‐SY5Y cells to CDDP 2.5 μg/ml induced a reduction of the neurite length and of the percentage of differentiated cells. The co‐treatment of RA‐differentiated SH‐SY5Y neuroblastoma cells with CDDP and rhBDNF restored the neurite length and the percentage of differentiated cells to values similar to those of cells treated with RA 10 μM alone. On the contrary, exposure of RA‐differentiated SH‐SY5Y neuroblastoma cells to rhNT‐3/CDDP combination did not significantly modify the neurite length nor the percentage of differentiated cells in comparison to the cells treated with CDDP alone. The effect of rhNGF was intermediate between that of rhBDNF and the absence of any protection observed with rhNT‐3. Our results are in agreement with the observation that RA treatment induces the expression of functional trkB receptors in SH‐SY5Y cells, which results in BDNF‐mediated neuronal differentiation of SH‐SY5Y cells and explains the BDNF neuroprotective effect observed, while trkA receptors are expressed at a lower level and trkC receptors are not expressed even after RA‐induced differentiation.

Expression of TrkB receptors in developing visual cortex is not regulated by light.

1. Neurotrophins are very good candidates which relate electrical activity to molecular changes in activity-dependent phenomena. They exert their action through binding to specific tyrosine-kinase receptors: Trk receptors. It is important to consider Trk distribution in order to understand better the role of neurotrophins in the Central Nervous System (CNS). We focused our attention on brain-derived neurotrophic factor (BDNF) Trk receptors (TrkB) during development of the rat visual cortex, since this neurotrophin has been shown to play an important role in visual system development and plasticity. 2. We investigated the full length form of TrkB receptors considering both its total amount and its cellular distribution. To address this issue we used an antibody that recognizes the full length form of TrkB and we used it both in Western blot and immunohistochemistry. 3. We found that the expression of TrkB receptor increases during development, but that there is no effect on visual experience, since dark-reared animals show the same protein level and pattern of TrkB expression compared to age-matched, normally reared controls.

Changes in Truncated trkB and p75 Receptor Expression in the Rat Spinal Cord Following Spinal Cord Hemisection and Spinal Cord Hemisection plus Neurotrophin Treatment

Although numerous studies have examined the effects of neurotrophin treatment following spinal cord injury, few have examined the changes that occur in the neurotrophin receptors following either such damage or neurotrophin treatment. To determine what changes occur in neurotrophin receptor expression following spinal cord damage, adult rats received a midthoracic spinal cord hemisection alone or in combination with intrathecal application of brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3). Using immunohistochemical and in situ hybridization techniques, p75, trkA, trkB, and trkC receptor expression was examined throughout the spinal cord. Results showed that trkA, full-length trkB, and trkC receptors were not present in the lesion site but had a normal expression pattern in uninjured parts of the spinal cord. In contrast, p75 receptor expression occurred on Schwann cells throughout the lesion site. BDNF and NT-3 (but not saline) applied to the lesion site increased this expression. In addition, the truncated trkB receptor was expressed in the border between the lesion and intact spinal cord. Truncated trkB receptor expression was also increased throughout the white matter ipsilateral to the lesion and BDNF (but not NT-3 or saline) prevented this increase. The study is the first to show changes in truncated trkB receptor expression that extend beyond the site of a spinal cord lesion and is one of the first to show that BDNF and NT-3 affect Schwann cells and/or p75 expression following spinal cord damage. These results indicate that changes in neurotrophin receptor expression following spinal cord injury could influence the availability of neurotrophins at the lesion site. In addition, neurotrophins may affect their own availability to damaged neurons by altering the expression of the p75 and truncated trkB receptor.

Compartmental expression of trkB receptor protein in the developing striatum

To investigate the role of neurotrophins in the initial formation of striatal patch versus matrix, the spatial and temporal expression of trkB receptors was examined using immunohistochemistry. Polyclonal antibodies, against the C-terminus or the tyrosine kinase domain, revealed trkB-immunoreactive cells and fibers localized to patches beginning on embryonic day 19 in the rat, which co-localized with patchy dopamine fibers, substance P-immunoreactive neurons and glutamate receptors. Patchy striatal trkB expression was maintained after lesioning the nigrostriatal dopamine system. The patchy trkB distribution persisted through postnatal day 14, then became more homogeneous at the same time that nigrostriatal afferents become homogeneous. Later in development, trkB immunoreactivity was most intense in a subpopulation of large striatal cells that were similar in size and frequency to those immunoreactive for choline acetyltransferase. The spatiotemporal expression of trkB receptor in phenotypically distinct striatal patches, as well as evidence that neurotrophins regulate expression of neuronal phenotypic markers during development, may indicate a convergence of neurotrophins and afferent innervation on to future patch cells that may regulate the establishment of striatal compartmentalization.

Expression of a dominant negative TrkB receptor, T1, reveals a requirement for presynaptic signaling in BDNF-induced synaptic potentiation in cultured hippocampal neurons.

We have developed a method to analyze the relative contributions of pre- and postsynaptic actions of a particular gene product in neurons in culture and potentially in slices using adenovirus-mediated gene transfer. A recombinant virus directed the expression of both a GFP reporter protein and TrkB.T1, a C-terminal truncated dominant negative TrkB neurotrophin receptor. When expressed in the presynaptic cell at synapses between embryonic hippocampal neurons in culture, the dominant negative TrkB.T1 inhibited two forms of synaptic potentiation induced by the neurotrophin brain-derived neurotrophic factor (BDNF): (i) greater evoked synaptic transmission and (ii) higher frequency of spontaneous miniature synaptic currents. These inhibition effects are not seen if the transgene is expressed only in the postsynaptic cell. We conclude that BDNF-TrkB signal transduction in the presynaptic terminal leads to both types of potentiation and is therefore the primary cause of synaptic enhancement by BDNF in these neurons.

Enhanced expression of full-length TrkB receptors in young rat brain with hypoxic/ischemic injury

Expression of TrkB receptors were studied in the cerebral cortex of normal rats and young rats with hypoxic/ischemic injury. TrkB expressing cells were present in the piriform cortex at birth and increased in number with age, and were finally present in the entire cerebral cortex. Density of TrkB cells reached adult levels at P30. They were morphologically regarded as pyramidal neurons and interneurons. Hypoxic/ischemic injury induced a tentative increase of full-length TrkB receptors. A novel appearance of TrkB expressing neurons and enhanced immunostaining on both cell soma and dendrites were observed in the peri-infarct areas and increased number of TrkB expressing neurons were detected in the contralateral cortex after carotid artery ligation. This increase was no longer evident after 48 h of hypoxia. Double immunostaining using antiserum against GFA or OX-42 revealed no co-localization of TrkB receptors and these molecules, while there were only slight co-localization of TrkB and calbindin-D28k molecules. The altered levels in responses to injury indicate that TrkB may play a crucial role in the early protective mechanism of the neurons with hypoxic/ischemic injury through ligands BDNF and/or NT-4/5.

BDNF and NT-4/5 Prevent Atrophy of Rat Rubrospinal Neurons after Cervical Axotomy, Stimulate GAP-43 and Tα1-Tubulin mRNA Expression, and Promote Axonal Regeneration

Rubrospinal neurons (RSNs) undergo a marked atrophy in the second week after cervical axotomy. This delayed atrophy is accompanied by a decline in the expression of regeneration-associated genes such as GAP-43 and Talpha1-tubulin, which are initially elevated after injury. These responses may reflect a deficiency in the trophic support of axotomized RSNs. To test this hypothesis, we first analyzed the expression of mRNAs encoding the trk family of neurotrophin receptors. In situ hybridization revealed expression of full-length trkB receptors in virtually all RSNs, which declined 7 d after axotomy. Full-length trkC mRNA was expressed at low levels. Using RT-PCR, we found that mRNAs encoding trkC isoforms with kinase domain inserts were present at levels comparable to that for the unmodified receptor. TrkA mRNA expression was not detected in RSNs, and the expression of p75 was restricted to a small subpopulation of axotomized cells. In agreement with the pattern of trk receptor expression, infusion of recombinant human BDNF or NT-4/5 into the vicinity of the axotomized RSNs, between days 7 and 14 after axotomy, fully prevented their atrophy. This effect was still evident 2 weeks after the termination of BDNF treatment. Moreover, BDNF or NT-4/5 treatment stimulated the expression of GAP-43 and Talpha1-tubulin mRNA and maintained the level of trkB expression. Vehicle, NGF, or NT-3 treatment had no significant effect on cell size or GAP-43 and Talpha1-tubulin expression. In a separate experiment, infusion of BDNF also was found to increase the number of axotomized RSNs that regenerated into a peripheral nerve graft. Thus, in BDNF-treated animals, the prevention of neuronal atrophy and the stimulation GAP-43 and Talpha1-tubulin expression is correlated with an increased regenerative capacity of axotomized RSNs.

Expression of full-length trkB receptors by reactive astrocytes after chronic CNS injury.

Growth factors, including members of the neurotrophin family, are expressed by neuronal and glial elements following injury to the CNS. In order to assess the capacity for glial cells to respond to neurotrophins at sites of chronic injury, full-length trkB receptors were localized following implantation of a nitrocellulose filter into the cerebral cortex for 30 days. Northern analysis demonstrated that filter implants contained cells expressing transcripts for full-length and truncated trkB receptors, in contrast to the predominant expression of truncated trkB receptors by cultured astrocytes. In situ hybridization and immunohistochemistry using probes to the trkB kinase domain colocalized full-length receptors with GFAP-immunopositive reactive astrocytes adjacent to and within the filter implant. In contrast, OX-42-immunopositive microglia/macrophages were not stained for full-length trkB. These data indicate that reactive astrocytes can express functional trkB receptors following a chronic insult to the cerebral cortex and support the hypothesis that neurotrophins may regulate astrocytic responses to injury.

Short-term response of postnatal rat vestibular neurons following brain-derived neurotrophic factor or neurotrophin-3 application.

The effects of the application of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) neurotrophins on the intracellular calcium level ([Ca2+]i) were studied in vestibular ganglion neurons (VGNs) from postnatal day 3 (P3) rats cultured for 50 hr. We first assessed the expression of trkB and trkC mRNA receptors in cultured VGNs. Immunobloting and immunocytochemistry confirmed the presence of the neurotrophin receptors on neurons. Both neurotrophins induced transient [Ca2+]i elevations in VGNs: BDNF-treated neurons responded in 65% and NT-3-treated neurons in 56%. The responses could be inhibited by anti-BDNF or anti-NT-3 antibodies. The [Ca2+]i elevation was dependent on extracellular calcium since it was abolished in calcium-free medium but also implicates the release of calcium from intracellular stores as tested by prior depletion with thapsigargin. Our results suggest the implication of a short-term calcium regulation in VGNs, which could reflect specific fast effects of neurotrophins in the early postnatal rat vestibular system.

Expression of neurotrophin receptor trkB in rat cochlear hair cells at time of rearrangement of innervation.

The spatio-temporal distribution of the high-affinity neurotrophin receptor trkB was monitored during postnatal development of the rat cochlea. In addition to expression in presumptive afferent type I collaterals, afferent type II fibers, and efferent fibers, trkB immunoreactivity also transiently appeared in the sensory hair cells themselves, from postnatal days 5-9 in the basal turn, and from postnatal days 9-13 in the apical turn. A comparison of trkB with p75(NGFR), which is expressed in afferent and efferent fibers, and GAP-43 and synaptophysin, which are expressed in efferent fibers, revealed a time/space correlation of trkB receptor expression in hair cells with the rearrangement of their innervation. Co-expression of the neurotrophin receptor and its ligand has been proposed to be functionally involved in regulating the survival of neurons independent of target-derived neurotrophin factor. Thus, the presence of trkB in target hair cells, suggests that auto/paracrine mechanisms play a role during this critical period of rearrangement of neural connections.

The survival response of mesencephalic dopaminergic neurons to the neurotrophins BDNF and NT-4 requires priming with serum: comparison with members of the TGF-beta superfamily and characterization of the serum-free culture system.

The neurotrophins, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4), are established survival promoting molecules for dopaminergic (DAergic) neurons cultured from the fetal rat midbrain floor. We have cultured and compared the survival of embryonic day (E) 14 mesencephalic cells in fully defined, serum-free medium, with serum-primed cultures (one hour during dissociation). Cultures were characterized using antibodies against neuron-specific enolase (NSE), tyrosine hydroxylase (TH), vimentin, glial fibrillary acidic protein (GFAP), and the antigen A2B5. The absolute absence of serum did not reduce the survival of TH-positive DAergic neurons nor alter the percentages of cells staining for the above markers. Transforming growth factor-beta 3 (TGF-beta 3) and glial cell line-derived neurotrophic factor (GDNF), two members of the TGF-beta superfamily, both promoted the survival of TH-positive cells (TGF-beta 3: 2-fold; GDNF: 1.6-fold) over the 8-day culture period. Survival mediated by TGF-beta 3 and GDNF was independent of whether or not the cells had been initially exposed to serum. In contrast, the survival promoting effects of BDNF and NT-4 were crucially dependent on serum priming. RT-PCR for the full-length trkB high affinity neurotrophin receptor revealed its presence in both culture systems. We conclude that priming with serum is important to make DAergic neurons fully responsive to BDNF and NT-4. Underlying mechanisms might be sought at the level or distal of trkB receptor expression, without excluding the possiblity that serum elicits production of growth factors that synergistically act with neurotrophins in these cultures.

Differential regulation of catalytic and non-catalytictrkB messenger RNAs in the rat hippocampus following seizures induced by systemic administration of kainate

Ribonuclease protection analysis and quantitative in situ hybridization histochemistry were used to investigate the coordination and regional expression of catalytic and non-catalytic trkB messenger RNAs in the adult rat hippocampus following systemic kainate-induced seizures. Changes in trkB expression were compared with the messenger RNA expression of its neurotrophic ligands, brain-derived neurotrophic factor and neurotrophin-3. TrkB messenger RNA expression was increased in the dentate granule cells at 1-4 h following the onset of seizures, and returned to control levels 16-24 h thereafter. In addition, seizures also induced expression of trkB messenger RNA in putative non-neuronal cells at four to seven days in the molecular layer of the dentate gyrus and the stratum lacunosum moleculare of the CA1 region. Hybridization with probes specific for the non-catalytic trkB receptor and the catalytic trkB receptor revealed that the increases at four and seven days in the molecular layers of the hippocampus reflected an up-regulation of only the non-catalytic form of the receptor. Furthermore, the neuronal increases observed 1-4 h were due to an up-regulation of both trkB TK- and trkB TK+ messenger RNAs. It was established that systemic administration of kainate increased brain-derived neurotrophic factor messenger RNA levels in the pyramidal and granule cell regions of the hippocampus 1-4 h following the onset of behaviorally manifested seizure activity. Early changes in neuronal expression of trkB TK- and trkB TK+ messenger RNA paralleled changes in brain-derived neurotrophic factor messenger RNA in the dentate granule cell and CA1 pyramidal cell layers, but not in the CA3 subregion. These data suggest that concomitant regulation of brain-derived neurotrophic factor and its cognate receptor may play a role in the selective vulnerability of hippocampal subregions to kainate-induced neuropathology. Furthermore, these data suggest a dual function for trkB receptor expression in the hippocampus following kainate-induced seizures, possibly related to both the plastic and degenerative consequences of seizure induction by kainate.

Retinoic acid induces BDNF responsiveness of sympathetic neurons by alteration of Trk neurotrophin receptor expression

The expression of high affinity neurotrophin receptors (TrkA, TrkB, and TrkC) determines the survival response of different populations of neurons to specific members of the neurotrophin family, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3). However, the mechanism which controls the expression of neurotrophin receptors during neuronal development is largely unknown. Here we show that the treatment of the cultured sympathetic neurons from newborn rat superior cervical ganglia (SCG) with retinoic acid (RA), a derivative of vitamin A, suppressed the expression of trkA mRNA and induced the expression of trkB mRNA. Expression of the functional TrkB receptor was confirmed by the emergence of trophic dependence of these neurons on BDNF in the absence of NGF. Differential regulation of trk mRNAs by RA provides a possible model for the establishment of neurotrophin dependence of peripheral neurons.

Developmental expression of trkB and low-affinity NGF receptor in the rat retina

Brain-derived neurotrophic factor (BDNF) promotes the survival of retinal ganglion cells, but these effects are dependent on the developmental stages, and a number of retinal ganglion cells are eliminated during pre- and neonatal stages. We have examined the expression of BDNF receptors, trkB and low-affinity nerve growth factor receptor (LNGFR), in the rat retina during these period using Northern blot analysis. The expression of trkB and LNGFR displayed two peaks during embryonic day 17 (E17) through postnatal day 1 (P1), and during P14–P17, indicating that it may play an important role in neuronal development and neuronal cell death.

Nerve growth factor.

Nerve growth factor.