Wnt Pathway – Long Term Memory and Autism

Scripps Florida Scientists Pinpoint Proteins Vital to Long-Term Memory

http://www.scripps.edu/news/press/2013/20130912davis.html

JUPITER, FL – September 12, 2013 – Scientists from the Florida campus of The Scripps Research Institute (TSRI) have found a group of proteins essential to the formation of long-term memories.

The study, published online ahead of print on September 12, 2013 by the journal Cell Reports, focuses on a family of proteins called Wnts. These proteins send signals from the outside to the inside of a cell, inducing a cellular response crucial for many aspects of embryonic development, including stem cell differentiation, as well as for normal functioning of the adult brain.

“By removing the function of three proteins in the Wnt signaling pathway, we produced a deficit in long-term but not short-term memory,” said Ron Davis, chair of the TSRI Department of Neuroscience. “The pathway is clearly part of the conversion of short-term memory to the long-term stable form, which occurs through changes in gene expression.”

The findings stem from experiments probing the role of Wnt signaling components in olfactory memory formation in Drosophila, the common fruit fly—a widely used doppelgänger for human memory studies. In the new study, the scientists inactivated the expression of several Wnt signaling proteins in the mushroom bodies of adult flies—part of the fly brain that plays a role in learning and memory.

The resulting memory disruption, Davis said, suggests that Wnt signaling participates actively in the formation of long-term memory, rather than having some general, non-specific effect on behavior.

“What is interesting is that the molecular mechanisms of adult memory use the same processes that guide the early development of the organism, except that they are repurposed for memory formation,” he said. “One difference, however, is that during early development the signals are intrinsic, while in adults they require an outside stimulus to create a memory.”

The first author of the study, “Wnt signaling is required for long-term memory formation,” is Ying Tan of the Baylor College of Medicine. Other authors include Germain U. Busto of TSRI and Curtis Wilson of Baylor College of Medicine.

The study was supported by the National Institutes of Health (NS19904).

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Wnt Pathways and Autism

A review of the evidence for the canonical Wnt pathway in autism spectrum disorders

http://www.molecularautism.com/content/3/1/10

Microdeletion and microduplication copy number variations are found in patients with autism spectrum disorder and in a number of cases they include genes that are involved in the canonical Wnt signaling pathway (for example, FZD9, BCL9 or CDH8).

Association studies investigating WNT2, DISC1, MET, DOCK4 or AHI1 also provide evidence that the canonical Wnt pathway might be affected in autism.

Prenatal medication with sodium-valproate or antidepressant drugs increases autism risk. In animal studies, it has been found that these medications promote Wnt signaling, including among others an increase in Wnt2 gene expression.

Notably, the available genetic information indicates that not only canonical Wnt pathway activation, but also inhibition seems to increase autism risk.

The canonical Wnt pathway plays a role in dendrite growth and suboptimal activity negatively affects the dendritic arbor. In principle, this provides a logical explanation as to why both hypo- and hyperactivity may generate a similar set of behavioral and cognitive symptoms.

However, without a validated biomarker to stratify for deviant canonical Wnt pathway activity, it is probably too dangerous to treat patients with compounds that modify pathway activity.

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Wnt Pathway and Influenza

A physical and regulatory map of host-influenza interactions reveals pathways in H1N1 infection

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892837/

During the course of a viral infection, viral proteins interact with an array of host proteins and pathways.

Here we present a systematic strategy to elucidate the dynamic interactions between H1N1 influenza and its human host. A combination of yeast two hybrid analysis and genome-wide expression profiling implicated hundreds of human factors in mediating viral-host interactions. These factors were then examined functionally through depletion analyses in primary lung cells.

The resulting data point to potential roles for some unanticipated host and viral proteins in viral infection and the host response, including a network of RNA binding proteins, components of WNT signaling and viral polymerase subunits. This multilayered approach provides a comprehensive and unbiased physical and regulatory model of influenza-host interactions, and demonstrates a general strategy for uncovering complex host-pathogen relationships.

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