Proteolysis of proBDNF Is a Key Regulator in the Formation of Memory

It is essential to understand the molecular processes underlying long-term memory to provide therapeutic targets of aberrant memory that produce pathological behaviour in humans. Under conditions of recall, fully-consolidated memories can undergo reconsolidation or extinction. These retrieval-mediated memory processes may rely on distinct molecular processes. The cellular mechanisms initiating the signature molecular events are not known. Using infusions of protein synthesis inhibitors, antisense oligonucleotide targeting brain-derived neurotrophic factor (BDNF) mRNA or tPA-STOP (an inhibitor of the proteolysis of BDNF protein) into the hippocampus of the awake rat, we show that acquisition and extinction of contextual fear memory depended on the increased and decreased proteolysis of proBDNF (precursor BDNF) in the hippocampus, respectively. Conditions of retrieval that are known to initiate the reconsolidation of contextual fear memory, a BDNF-independent memory process, were not correlated with altered proBDNF cleavage. Thus, the processing of BDNF was associated with the acquisition of new information and the updating of information about a salient stimulus. Furthermore, the differential requirement for the processing of proBDNF by tPA in distinct memory processes suggest that the molecular events actively engaged to support the storage and/or the successful retrieval of memory depends on the integration of ongoing experience with past learning

The history of anatomy in Persia

The study of human anatomy can be found throughout the rich history of Persia. For thousands of years, morphological descriptions derived from this part of the world have contributed to and have helped form our current anatomical knowledge base. In this article we review the major influential Persian periods and the individuals who have contributed to the development of anatomy. We have divided the history of Persia into five eras: (1) the period of the Elamites, Medes, early Persians and Babylonians (10th millennium to 6th century BC); (2) following the establishment of the Persian Empire (6th century BC) to the 7th century AD; (3) after the Islamic conquest of Persia to the ascendency of Baghdad (7th to 13th century AD); (4) from the Mongol invasion of Persia to the foundations of modern anatomy (13th to 18th century AD); and (5) modern Persia/Iran (18th century AD to present). Evidence indicates that human dissection was commonplace in the first era, which led to a disciplined practice of surgery in the centuries leading to the foundation of the Persian Empire. By the emergence of Zoroastrianism in the Persian Empire, the microcosm theory was widely used to understand internal anatomy in relation to the external universe. The world's first cosmopolitan university and hospital were built in Gondishapur, south-western Persia, in the third century AD. Greek and Syriac knowledge influenced the second era. With the gradual ruin of Gondishapur and the foundation of Baghdad following the Islamic conquest of Persia (637–651 AD), a great movement took place, which led to the flourishing of the so-called Middle Age or Islamic Golden Age. Of the influential anatomists of this period, Mesue (777–857 AD), Tabbari (838–870 AD), Rhazes (865–925 AD), Joveini (?−983 AD), Ali ibn Abbas (930–994 AD), Avicenna (980–1037 AD) and Jorjani (1042–1137 AD) all hailed from Persia. There is evidence in the Persian literature as to the direct involvement of these scholars in human dissection. Syro-Indian, Byzantine, Greek, Chinese and Arabic knowledge all influenced the third era. In the fourth period, the first colour illustrated anatomical text (by Mansur, 14th century AD) was compiled. Chinese and Indian anatomical styles were embraced, though there was a strong religious siege of anatomy late in this era. By the 19th century, Persia had entered a new era of modernizing movements and academic contact with the West through the reforms of Mirza Tagi Khan Amir Kabir. Knowledge of anatomy for this region in the 20th century was greatly influenced by Europe and America

Spatial monitoring of toxicity in HMOX-LacZ transgenic mice

Chantier qualité GATransgenic reporter mice can contribute in the development of less toxic and more selective drugs to treat disease. In this brief communication we describe the generation and initial validation of transgenic mice that provide a visual spatial readout of oxidative stress. These mice carry a LacZ reporter transgene driven by the human haem oxygenase 1 promoter. The induction of LacZ staining by a range of compounds indicated differences in the haem oxygenase 1 spatial response within a tissue. Thus this transgene allows for the spatial monitoring of differences in toxic insult and indicates that this type of transgenic system could have use in toxicity screens

Schwann cell myelination requires Dynein function

<p>Abstract</p> <p>Background</p> <p>Interaction of Schwann cells with axons triggers signal transduction that drives expression of Pou3f1 and Egr2 transcription factors, which in turn promote myelination. Signal transduction appears to be mediated, at least in part, by cyclic adenosine monophosphate (cAMP) because elevation of cAMP levels can stimulate myelination in the absence of axon contact. The mechanisms by which the myelinating signal is conveyed remain unclear.</p> <p>Results</p> <p>By analyzing mutations that disrupt myelination in zebrafish, we learned that Dynein cytoplasmic 1 heavy chain 1 (Dync1h1), which functions as a motor for intracellular molecular trafficking, is required for peripheral myelination. In <it>dync1h1</it> mutants, Schwann cell progenitors migrated to peripheral nerves but then failed to express Pou3f1 and Egr2 or make myelin membrane. Genetic mosaic experiments revealed that robust Myelin Basic Protein expression required Dync1h1 function within both Schwann cells and axons. Finally, treatment of <it>dync1h1</it> mutants with a drug to elevate cAMP levels stimulated myelin gene expression.</p> <p>Conclusion</p> <p>Dync1h1 is required for retrograde transport in axons and mutations of Dync1h1 have been implicated in axon disease. Our data now provide evidence that Dync1h1 is also required for efficient myelination of peripheral axons by Schwann cells, perhaps by facilitating signal transduction necessary for myelination.</p