A medial temporal lobe division of labor: Insights from memory in aging and early Alzheimer disease

Dual process theories of recognition memory posit that recollection and familiarity represent dissociable processes. Animal studies and human functional imaging experiments support an anatomic dissociation of these processes in the medial temporal lobes (MTL). By this hypothesis, recollection may be dependent on the hippocampus, while familiarity appears to rely on extrahippocampal MTL (ehMTL) structures, particularly perirhinal and lateral entorhinal cortices. Despite these findings, the dual process model and these anatomic mappings remain controversial, in part because the study of patients with lesions to the MTL has been limited and has revealed predominantly single dissociations. We examined measures of recollection and familiarity in three groups (normal older adults, amnesic‐mild cognitive impairment, Alzheimer's disease) in which these memory measures and the relative integrity of MTL structures are variable, thus enhancing our power to detect MTL‐memory relationships. Recollection and familiarity and volumes of hippocampus and ehMTL, defined as a region including entorhinal/perirhinal cortices and parahippocampus, were measured. Regression analyses revealed a stronger relationship of recollection with the hippocampus compared to ehMTL, while familiarity was more highly related to ehMTL compared to hippocampus. These results are consistent with a division of labor in the MTL and the dual process model. © 2010 Wiley‐Liss, Inc.     

Editorial Commentary: An Alternative to Opioids? Adhesive Drapes and Chlorhexidine Skin Preparation May Reduce Propionibacterium acnes–Related Pain After Shoulder Surgery

Propionibacterium acnes has long been known to play a detrimental role in shoulder surgery. This thoughtful and revealing study found significant evidence of lower rates of P. acnes cultured during arthroscopic rotator cuff repair with the use of an adhesive drape and chlorhexidine skin preparation.     

Activation of the p53 pathway by small-molecule-induced MDM2 and MDMX dimerization

Activation of p53 tumor suppressor by antagonizing its negative regulator murine double minute (MDM)2 has been considered an attractive strategy for cancer therapy and several classes of p53-MDM2 binding inhibitors have been developed. However, these compounds do not inhibit the p53-MDMX interaction, and their effectiveness can be compromised in tumors overexpressing MDMX. Here, we identify small molecules that potently block p53 binding with both MDM2 and MDMX by inhibitor-driven homo- and/or heterodimerization of MDM2 and MDMX proteins. Structural studies revealed that the inhibitors bind into and occlude the p53 pockets of MDM2 and MDMX by inducing the formation of dimeric protein complexes kept together by a dimeric small-molecule core. This mode of action effectively stabilized p53 and activated p53 signaling in cancer cells, leading to cell cycle arrest and apoptosis. Dual MDM2/MDMX antagonists restored p53 apoptotic activity in the presence of high levels of MDMX and may offer a more effective therapeutic modality for MDMX-overexpressing cancers.     

Membrane-bound choline acetyltransferase is a cell surface marker of the differentiated NS-20Y cholinergic cell line

When differentiated cells of the cholinergic NS-20Y type were incubated with an antiserum to choline acetyltransferase (ChAT), in the presence of complement, immunolysis occurred as demonstrated by release of 20% of total lactate dehydrogenase and 70% of total ChAT. No significant immunolytic effects were observed when either undifferentiated (dividing or non-dividing) or partially differentiated cells were incubated under identical conditions. When the Triton X-114 phase separation technique was employed using membranes from differentiated cells, a small but significant proportion of choline acetyltransferase was recovered in the detergent-rich phase. These results suggest that a membrane-bound form of ChAT is a surface marker of the NS-20Y cell line.     

Anticonvulsant action of amino acid antagonists against kindled hippocampal seizures

Single unit recordings were made from neurons of the subfornical organ (SFO) in hemispherectomized cats following electrical stimulation in the paraventricular nucleus (PVN) of the hypothalamus. Of 132 neurons tested, 48 (36%) were inhibited, 3 (2.3%) excited and two (1.5%) antidromically activated. In separate experiments the wall of the third ventricle near the PVN was locally perfused with glutamate solution using a concentric push-pull cannula. Of 35 SFO neurons tested, 6 were inhibited, 5 were facilitated and 24 unaffected. The results indicate that one-third of SFO neurons receive synaptic inputs from cells in or near the PVN.