Expression of GAP-43 during development and after monocular enucleation in the rat superior colliculus

Abstract

The retinotectal projection of rodents presents a precise retinotopic organization that develops, from diffuse connections, from the day of birth to post-natal day 10. Previous data had demonstrated that these projections undergo reorganization after retinal lesions, nerve crush and monocular enucleation. The axonal growth seems to be directly related to growth-associated protein-43 (GAP-43) expression, a protein predominantly located in growth cones, which is regulated throughout development. GAP-43 is presented both under non-phosphorylated and phosphorylated (pGAP-43) forms. The phosphorylated form, has been associated to axon growth via polymerization of F-actin, and synaptic enhancement through neurotransmitter release facilitation. Herein we investigated the spatio-temporal expression of GAP-43 in the rat superior colliculus during normal development and after monocular enucleation in different stages of development. Lister Hooded rats ranging from post-natal day 0 to 70 were used for ontogeny studies. Another group of animals were submitted to monocular enucleation at post-natal day 10 (PND10) or PND21. After different survival-times, the animals were sacrificed and the brains processed for either immunohistochemistry or western blotting analysis. Our data show that GAP-43 is expressed in retinotectal axons in early stages of development but remains present in adulthood. Moreover, monocular enucleation leads to an increase in pGAP-43 expression in the deafferented colliculus. Taken together these results suggest a role for pGAP-43 in retinotectal morphological plasticity observed both during normal development and after monocular enucleation.

Passive Exercise of the Hind Limbs after Complete Thoracic Transection of the Spinal Cord Promotes Cortical Reorganization

“…This exercise protocol is based on previous work showing that at least 1 week of hindlimb bike exercise after spinal cord injury is necessary to induce significant plastic changes in the spinal cord below the level of the lesion (Keeler et al, 2009). We focused on the following 6 proteins known to be involved in neuronal plasticity in the brain: ADCY1, BDNF and its receptor trkB, GAP43, LINGO-1 and p35 [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62]. Data from ‘bike-exercise’ and ‘sham-exercise’ animals were expressed as percentage of normal animals (as in [46]).…”

“…Our study further shows that other proteins known to be associated with different aspects of morphological and functional plasticity are regulated after spinal cord transection. These include ADCY1, which is involved in long-term synaptic plasticity, learning and memory [51]; GAP43, which is critical for the normal establishment of ordered topography in the developing barrel cortex [67], [68] and mediates functional recovery after lesions in the adult central nervous system [21], [57], [60]; p35, which is regulated in neurodegeneration [61], has an important neuroprotective role in vivo [49] and contributes to different forms of synaptic plasticity [62]. A complex network of proteins is therefore involved in cortical reorganization after spinal cord injury.…”

Rapamycin promotes Schwann cell migration and nerve growth factor secretion

“…The molecular mechanisms underlying the stimulating effects of FK506 on peripheral nerve regeneration have been reported[3233]. FKBP-12 binding and calcineurin inhibition can increase the phosphorylation of several substrates, such as growth-associated protein 43, which significantly affects neural plasticity and is highly expressed in regenerative growth cones[34]. Non-immunosuppressant derivatives of FK506 do not inhibit calcineurin, but accelerate nerve regeneration.…”

The Impact of Low Omega-3 Fatty Acids Diet on the Development of the Visual System

“…35 The closure of the critical period in the primary visual cortex involves extracellular matrix (ECM) molecules that develop an environment that inhibits axon and dendritic remodeling. 16,40,41 Those experiments revealed that the plastic capacity of retinocollicular connections during the critical period is characterized by a rapid reactive growth of axons from the nonlesioned eye in response to lesions during the first 3 postnatal weeks. 38 In visual subcortical nuclei such as the SC, the critical period overlaps with the period of fine tuning of topographical maps.…”

“…Lipid levels were measured in samples from the collicular visual layers of rats at PND28. 40,108 The disturbance of visual system development induced by omega-3/DHA reduction was not confined 13 The topographical distribution of uncrossed retinocollicular terminal fields was determined by the anterograde transport of horseradish peroxidase (HRP) as an anterograde tracer.…”