Procollagen alpha2 mRNA is significantly different from procollagen alpha1(I) mRNA in size or secondary structure.

The fractionation of fetal calf tendon messenger RNA in 85 percent formamide sucrose gradients shows a separation of the mRNAs coding for pro α1(I) and pro α2 chains of type I collagen. This difference in sedimentation in denaturing gradients suggests that pro α2 mRNA is approxmately 1000 bases shorter than pro α1(I) mRNA. However, such a size difference is significantly greater than would be predicted from consideration of the size of the polypeptide chains coded for by these mRNAs, and thus, residual secondary structure in the mRNAs may contribute to these apparent size differences.     

β-Amyloid (Aβ) Oligomers Impair Brain-derived Neurotrophic Factor Retrograde Trafficking by Down-regulating Ubiquitin C-terminal Hydrolase,UCH-L1

We previously found that BDNF-dependent retrograde trafficking is impaired in AD transgenic mouse neurons. Utilizing a novel microfluidic culture chamber, we demonstrate that Aβ oligomers compromise BDNF-mediated retrograde transport by impairing endosomal vesicle velocities, resulting in impaired downstream signaling driven by BDNF/TrkB, including ERK5 activation, and CREB-dependent gene regulation. Our data suggest that a key mechanism mediating the deficit involves ubiquitin C-terminal hydrolase L1 (UCH-L1), a deubiquitinating enzyme that functions to regulate cellular ubiquitin. Aβ-induced deficits in BDNF trafficking and signaling are mimicked by LDN (an inhibitor of UCH-L1) and can be reversed by increasing cellular UCH-L1 levels, demonstrated here using a transducible TAT-UCH-L1 strategy. Finally, our data reveal that UCH-L1 mRNA levels are decreased in the hippocampi of AD brains. Taken together, our data implicate that UCH-L1 is important for regulating neurotrophin receptor sorting to signaling endosomes and supporting retrograde transport. Further, our results support the idea that in AD, Aβ may down-regulate UCH-L1 in the AD brain, which in turn impairs BDNF/TrkB-mediated retrograde signaling, compromising synaptic plasticity and neuronal survival.     

Validation of a rodent model of source memory

Source memory represents the origin (source) of information. Recently, we proposed that rats (Rattus norvegicus) remember the source of information. However, an alternative to source memory is the possibility that rats selectively encoded some, but not all, information rather than retrieving an episodic memory. We directly tested this ‘encoding failure’ hypothesis. Here, we show that rats remember the source of information, under conditions that cannot be attributed to encoding failure. Moreover, source memory lasted at least seven days but was no longer present 14 days after studying. Our findings suggest that long-lasting source memory may be modelled in non-humans. Our model should facilitate attempts to elucidate the biological underpinnings of source memory impairments in human memory disorders such as Alzheimer''s disease.