Brain-Derived Neurotrophic Factor Differentially Regulates Retinal Ganglion Cell Dendritic and Axonal ArborizationIn Vivo

Abstract

Expression of the neurotrophin brain-derived neurotrophic factor (BDNF) and its receptor trkB in the ganglion cell layer of the Xenopus retina during retinal ganglion cell (RGC) dendritic arborization indicates that BDNF is spatially and temporally available to influence RGC morphological differentiation (; ). BDNF promotes RGC axon arborization in vivo by acting as a target-derived trophic factor (). To determine whether BDNF also acts locally to regulate RGC dendritic development in vivo, we altered retinal neurotrophin levels at the onset of dendritic arborization and assessed the resulting arbor morphologies of RGCs retrogradely labeled with fluorescent dextrans. Injecting neurotrophins or BDNF function-blocking antibodies coupled to microspheres provided local alterations of retinal neurotrophin levels. BDNF significantly decreased RGC dendritic arbor complexity, whereas neutralizing endogenous BDNF levels with function-blocking antibodies significantly increased dendritic arbor complexity. RGCs exposed to other neurotrophins, as well as RGCs in retinae treated with BDNF but in areas not directly exposed to the neurotrophin, developed dendritic arbors that were indistinguishable from controls, indicating that exogenous BDNF acts specifically and locally. In the tectum, where RGC axons arborize, BDNF had opposite effects. BDNF significantly increased RGC axon arbor complexity and anti-BDNF reduced RGC arborization. Thus, BDNF reduces RGC dendritic arborization within the retina and increases axon arborization in the tectum. These results indicate that BDNF can differentially modulate axonal and dendritic arborization within a single neuronal population in opposing manners and raise the possibility that differential modulation by a neurotrophic factor finely tunes the morphological differentiation program of a neuron.

The N-terminal region of reelin regulates postnatal dendritic maturation of cortical pyramidal neurons

“…The morphological analysis was performed using Image J (National Institute of Health, Bethesda, MD; http://rsb.info.nih.gov/nihimage/), and the Neuron Morpho plug-in for reconstruction and the LMeasure software to define the parameters used to determine the dendritic complexity index (DCI). The DCI was calculated as previously described (37). Briefly, we assigned each branch tip an order value that equaled the number of branch points between the tip and the base of its primary dendrite.…”

Targeting the HDAC2/HNF-4A/miR-101b/AMPK Pathway Rescues Tauopathy and Dendritic Abnormalities in Alzheimer’s Disease

“…The dendritic complexity index was calculated for each neuron, as reported previously: DCI = [(sum of branch tip orders + number of branch tips)(total arbor length)/(number of primary dendrites)]. 43 The Sholl analysis was used to determine the complexity of dendrites, as previously described. 44 The dendritic spines were measured according to a previously reported method in two segments of 20 mm each (90-110 mm and 190-210 mm from the soma) on one of the main branches.…”

Exercise decreases myelin‐associated glycoprotein expression in the spinal cord and positively modulates neuronal growth

“…Infusion of TrkB-IgGs was achieved by coupling them to microbeads (Lumaflour Corp., Naples, FL), which we have previously used as a reservoir for the successful delivery of viable inhibitors into the hippocampus (Vaynman et al, 2003). Microbeads were coated via passive absorbency by incubating overnight at 4°C with a 1:5 mix of microbeads to TrkB-IgG 5 μg/μL in PBS with BSA, (Croll et al, 1998) or Cytochrome C (CytC) 100 ng/μL in sterile water (Lom and Cohen-Cory, 1999;Riddle et al, 1997). The solution was then centrifuged at 14,000g for 30 min and the microbeads were resuspended in sterile water at a 10% concentration.…”