Dataset Information

Impaired sprouting and axonal atrophy in cerebellar climbing fibres following in vivo silencing of the growth-associated protein GAP-43.

ABSTRACT: The adult mammalian central nervous system has a limited ability to establish new connections and to recover from traumatic or degenerative events. The olivo-cerebellar network represents an excellent model to investigate neuroprotection and repair in the brain during adulthood, due to its high plasticity and ordered synaptic organization. To shed light on the molecular mechanisms involved in these events, we focused on the growth-associated protein GAP-43 (also known as B-50 or neuromodulin). During development, this protein plays a crucial role in growth and in branch formation of neurites, while in the adult it is only expressed in a few brain regions, including the inferior olive (IO) where climbing fibres (CFs) originate. Following axotomy GAP-43 is usually up-regulated in association with regeneration. Here we describe an in vivo lentiviral-mediated gene silencing approach, used for the first time in the olivo-cerebellar system, to efficiently and specifically downregulate GAP-43 in rodents CFs. We show that lack of GAP-43 causes an atrophy of the CF in non-traumatic conditions, consisting in a decrease of its length, branching and number of synaptic boutons. We also investigated CF regenerative ability by inducing a subtotal lesion of the IO. Noteworthy, surviving CFs lacking GAP-43 were largely unable to sprout on surrounding Purkinje cells. Collectively, our results demonstrate that GAP-43 is essential both to maintain CFs structure in non-traumatic condition and to promote sprouting after partial lesion of the IO.

SUBMITTER: Grasselli G

PROVIDER: S-EPMC3112224 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Impaired sprouting and axonal atrophy in cerebellar climbing fibres following in vivo silencing of the growth-associated protein GAP-43.

Grasselli Giorgio G Mandolesi Georgia G Strata Piergiorgio P Cesare Paolo P

PloS one 20110610 6

The adult mammalian central nervous system has a limited ability to establish new connections and to recover from traumatic or degenerative events. The olivo-cerebellar network represents an excellent model to investigate neuroprotection and repair in the brain during adulthood, due to its high plasticity and ordered synaptic organization. To shed light on the molecular mechanisms involved in these events, we focused on the growth-associated protein GAP-43 (also known as B-50 or neuromodulin). D ...[more]

PMID: 21695168

Similar Datasets

Project description:One of the primary theories of the pathogenesis of tinnitus involves maladaptive auditory?somatosensory plasticity in the dorsal cochlear nucleus (DCN), which is assumed to be due to axonal sprouting. Although a disrupted balance between auditory and somatosensory inputs may occur following hearing damage and may induce tinnitus, examination of this phenomenon employed a model of hearing damage that does not account for the causal relationship between these changes and tinnitus. The present study aimed to investigate changes in auditory?somatosensory innervation and the role that axonal sprouting serves in this process by comparing results between animals with and without tinnitus. Rats were exposed to a noise?inducing temporary threshold shift and were subsequently divided into tinnitus and non?tinnitus groups based on the results of gap prepulse inhibition of the acoustic startle reflex. DCNs were collected from rats divided into three sub?groups according to the number of weeks (1, 2 or 3) following noise exposure, and the protein levels of vesicular glutamate transporter 1 (VGLUT1), which is associated with auditory input to the DCN, and VGLUT2, which is in turn primarily associated with somatosensory inputs, were assessed. In addition, factors related to axonal sprouting, including growth?associated protein 43 (GAP43), postsynaptic density protein 95, synaptophysin, ??thalassemia/mental retardation syndrome X?linked homolog (ATRX), growth differentiation factor 10 (GDF10), and leucine?rich repeat and immunoglobulin domain?containing 1, were measured by western blot analyses. Compared to the non?tinnitus group, the tinnitus group exhibited a significant decrease in VGLUT1 at 1 week and a significant increase in VGLUT2 at 3 weeks post?exposure. In addition, rats in the tinnitus group exhibited significant increases in GAP43 and GDF10 protein expression levels in their DCN at 3 weeks following noise exposure. Results from the present study provided further evidence that changes in the neural input distribution to the DCN may cause tinnitus and that axonal sprouting underlies these alterations.

Dataset Information

Impaired sprouting and axonal atrophy in cerebellar climbing fibres following in vivo silencing of the growth-associated protein GAP-43.

Publications

Impaired sprouting and axonal atrophy in cerebellar climbing fibres following in vivo silencing of the growth-associated protein GAP-43.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets