Biomedical subjects

Pedro Bekinschtein

Publications and source records attributed to Pedro Bekinschtein.

3 recordsLinked to original sources

PubMed2004

One-trial aversive learning induces late changes in hippocampal CaMKIIalpha, Homer 1a, Syntaxin 1a and ERK2 protein levels.

Most studies regarding altered gene expression after learning are performed using multi-trial tasks, which do not allow a clear discrimination of memory acquisition, consolidation and retrieval. We screened for candidate memory-modulated genes in the hippocampus at 3 and 24 h after one-trial inhibitory avoidance (IA) training, using a cDNA array containing 1176 genes. While 33 genes were modulated by training (respect to shocked-only animals), most of them were upregulated (27 genes) and only 6 were downregulated. To confirm and extend these findings, we performed RT-PCRs and analyzed differences in protein levels in rat hippocampus using immunoblot assays. We found several proteins upregulated 24 h after training: extracellular signal-regulated kinase ERK2, Ca2+/calmodulin-dependent protein kinase II alpha (CaMKIIalpha), Syntaxin 1a, c-fos and Homer 1a. The total level of none of these proteins were found to be altered when measured 3-h post-training. Several of the mRNAs corresponding to the upregulated proteins were changed at 3 h but not 24 h. Additionally, a number of other candidates were identified for the first time as modulated by learning. The results presented here suggest that single-trial tasks can expose previously unseen differences in dynamic regulation of gene expression after behavioral manipulations, both at the transcriptional and translational levels, and reveal a diversity of gene products modulated by this task, allowing deeper understanding of the molecular basis of memory formation.

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PubMed2004

Gene expression during memory formation.

For several decades, neuroscientists have provided many clues that point out the involvement of de novo gene expression during the formation of long-lasting forms of memory. However, information regarding the transcriptional response networks involved in memory formation has been scarce and fragmented. With the advent of genome-based technologies, combined with more classical approaches (i.e., pharmacology and biochemistry), it is now feasible to address those relevant questions--which gene products are modulated, and when that processes are necessary for the proper storage of memories--with unprecedented resolution and scale. Using one-trial inhibitory (passive) avoidance training of rats, one of the most studied tasks so far, we found two time windows of sensitivity to transcriptional and translational inhibitors infused into the hippocampus: around the time of training and 3-6 h after training. Remarkably, these periods perfectly overlap with the involvement of hippocampal cAMP/PKA (protein kinase A) signaling pathways in memory consolidation. Given the complexity of transcriptional responses in the brain, particularly those related to processing of behavioral information, it was clearly necessary to address this issue with a multi-variable, parallel-oriented approach. We used cDNA arrays to screen for candidate inhibitory avoidance learning-related genes and analyze the dynamic pattern of gene expression that emerges during memory consolidation. These include genes involved in intracellular kinase networks, synaptic function, DNA-binding and chromatin modification, transcriptional activation and repression, translation, membrane receptors, and oncogenes, among others. Our findings suggest that differential and orchestrated hippocampal gene expression is necessary in both early and late periods of long-term memory consolidation. Additionally, this kind of studies may lead to the identification and characterization of genes that are relevant for the pathogenesis of complex psychiatric disorders involving learning and memory impairments, and may allow the development of new methods for the diagnosis and treatment of these diseases.

Amanitins↗

PubMed2002

Neonatal infection with a milk-borne virus is independent of beta7 integrin- and L-selectin-expressing lymphocytes.

Mouse mammary tumor virus (MMTV) is acquired by neonates through milk and first infects lymphocytes in Peyer's patches. We show here that newborn mice lacking beta7 integrin or L-selectin were infected with MMTV at wild-type levels in both their lymphoid and mammary tissues. Superantigen-mediated activation and cognate T cell deletion were also unimpaired in both types of null mice. A large proportion of neonatal Peyer's patch lymphocytes in wild-type mice were beta7 and beta1 integrin low and both populations increased in response to MMTV infection. These results suggest that adhesion molecules other than beta7 integrin or L-selectin play a role in lymphocyte homing in the gut, peripheral lymph nodes and mammary gland in response to MMTV infection.

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