Biomedical subjects

Jeffrey M Greenwood

Publications and source records attributed to Jeffrey M Greenwood.

3 recordsLinked to original sources

PubMed2003

ATF3 enhances c-Jun-mediated neurite sprouting.

The AP-1 transcription factor c-Jun is induced in axotomized neurons of the peripheral and central nervous systems, and in both cases upregulation of c-Jun expression has been correlated with axonal regeneration. More recently there has been interest in the c-Jun-related bZIP transcription factor, ATF3, and its function in neurons. ATF3 is also induced in nerve cells in response to axotomy and there is a correlation between increased ATF3 expression and upregulation of c-Jun in surviving neurons. Moreover, c-Jun is able to induce expression of ATF3. We investigated the effect of co-expressing c-Jun and ATF3 in two neuronal-like cell lines to model transcriptional events occurring in axotomized neurons undergoing regeneration. We show that expression of ATF3 with c-Jun significantly enhances c-Jun-mediated neurite sprouting, and that this phenotype is most likely mediated by a physical association of these two transcription factors. Our results suggest that a program of axonal regeneration is initiated when both c-Jun and ATF3 are upregulated in neurons in response to axotomy.

Activating Transcription Factor 3↗

PubMed2002

Induction and experience-dependent consolidation of stable long-term potentiation lasting months in the hippocampus.

Long-term potentiation (LTP) is widely regarded as a memory mechanism, but it is not known whether it can last long enough to underlie very long-term memory. We report that high-frequency stimulation (HFS) paradigms applied to the rat dentate gyrus can elicit stable LTP lasting months and up to at least 1 year. The induction of stable LTP was sensitive to stimulation variables on the day of HFS and was associated with phosphorylation of cAMP response element-binding protein. The maintenance of stable LTP was also experience-dependent, because it was reversed when animals were exposed repeatedly to an enriched environment beginning 14 d post-HFS. However, stable LTP eventually consolidated over time and became resistant to reversal, because exposure to enriched environments 90 d post-HFS failed to influence stable LTP maintenance. Thus, LTP can be shown to meet one of the principal criteria for a very long-term memory storage mechanism. However, under naturalistic environmental conditions, LTP may normally be retained in the hippocampus for only short periods of time.

Animals↗

PubMed2002

Muscarinic receptor-mediated phosphorylation of cyclic AMP response element binding protein in human neuroblastoma cells.

This study describes the effect of signalling through muscarinic acetylcholine receptors on two transcription factors implicated in long-term synaptic plasticity and memory formation, EGR1 and the cyclic AMP response element binding protein (CREB). In SK-N-SH neuroblastoma cells, treatment with the cholinergic agonist carbachol led to maximal induction of EGR1 1 h after stimulation. This was preceded by the phosphorylation of CREB, which peaked as early as 5 minutes after carbachol treatment. The levels of both EGR1 and phosphorylated CREB (pCREB) slowly decayed over 4-8 h. CREB phosphorylation and EGR1 induction showed similar sensitivity to carbachol concentration, with EC(50) values in the range of 1-10 microM, and the changes in both transcription factors were blocked by the muscarinic antagonist atropine. As has been described elsewhere, EGR1 induction was dependent on activation of p42/44 MAP kinase, as it was blocked by the MEK inhibitor U0126. However, CREB phosphorylation by carbachol was largely unaffected by MAP kinase blockade. As both CREB phosphorylation and EGR1 induction have been linked to long-term potentiation and some forms of memory consolidation, these results may implicate CREB and EGR1 in independent or partially independent cholinergic signalling pathways involved in memory processes.

Atropine↗