Reactive hippocampal sprouting in response to entorhinal cortex lesion demonstrates the ability for continued growth in the adult brain and can be used to identify mechanisms used by the brain to compensate for lost synapses. The mechanisms directing hippocampal sprouting are unknown. Interleukin-1beta (IL-1beta) and basic fibroblast growth factor (bFGF) increase in the hippocampus following entorhinal cortex lesion. We have recently demonstrated that the mRNA for insulin-like growth factor-1 (IGF-1) and ciliary neurotrophic factor (CNTF) increases in response to entorhinal Cortex lesion, with a spatial and temporal correspondence to the sprouting response. The goal of the proposed research is to evaluate if these growth factors collaborate to promote sprouting in the adult rat brain. This will be accomplished by (i) determining if CNTF protein is increased by deafferentation, (ii) testing if CNTF, IGF-1 or bFGF increases c-fos or tyrosine phosphorylation in commissural/associational neurons in vitro, (iii) testing if IL-1beta can regulate the gene expression of IGF-1 or CNTF in vitro, and (iv) determining if CNTF, IGF- 1 or bFGF promote sprouting in the organotypic slice preparation alone or synergistically. These studies will extend our knowledge of trophic factors that facilitate axonal plasticity in brain may suggest endogenous mechanisms of compensation for brain damage.
| Woods, A G; Poulsen, F R; Gall, C M (1999) Dexamethasone selectively suppresses microglial trophic responses to hippocampal deafferentation. Neuroscience 91:1277-89 |
| Woods, A G; Guthrie, K M; Kurlawalla, M A et al. (1998) Deafferentation-induced increases in hippocampal insulin-like growth factor-1 messenger RNA expression are severely attenuated in middle aged and aged rats. Neuroscience 83:663-8 |
| Guthrie, K M; Woods, A G; Nguyen, T et al. (1997) Astroglial ciliary neurotrophic factor mRNA expression is increased in fields of axonal sprouting in deafferented hippocampus. J Comp Neurol 386:137-48 |
