Orientation of myelin proteolipid protein in the oligodendrocyte cell membrane

The orientation of proteins within a cell membrane can often be difficult to determine. A number of models have been proposed for the orientation of the myelin protein, proteolipid protein (PLP), each of which includes exposed domains on the intracellular and extracellular membrane faces. Immunolabeling experiments have localized the C-terminus and the region spanning amino acids 103-116 to the cytoplasmic face of the membrane, but no well characterized antibodies have been available that label extracellular PLP domains. In this report, we describe the generation and characterization of mouse monoclonal antibodies (mAb) against putative extramembrane domains. Three of the mAb, specific for PLP peptides 40-59, 178-191, or: 215-232, immunostain!ive oligodendrocytes, indicating that these regions of the molecule are exposed on the external surface of the cell. In addition, we have used these mAb to study the time-course of incorporation of PLP into the oligodendrocyte membrane. These studies increase our knowledge of the orientation of PLP in the lipid bilayer and are relevant for understanding myelin function

Antidepressant Use and Orthostatic Hypotension in Older Adults Living with Mild-to-Moderate Alzheimer Disease

Objectives: Antidepressant use is often reported as a risk factor for Orthostatic Hypotension (OH), however this relationship has never been explored in those with mild/moderate Alzheimer Disease (AD), who may represent a particularly vulnerable cohort. Methods: We performed a cross-sectional analysis of baseline data from the NILVAD study. Participants with mild-moderate AD were recruited from 23 centres in 9 countries. Systolic and Diastolic Blood Pressure (SBP/DBP) was recorded in the seated position and after both 1 & 5 minutes of standing. OH was defined as a drop of 6520 mmHg SBP/ 65 10 mmHg DBP. We examined the relationship between antidepressant use, orthostatic BP drop and the presence of OH, controlling for important covariates. Results: Of 509 participants (72.9 \ub1 8.3 years, 61.9% female), two-fifths (39.1%; 199/509) were prescribed a regular antidepressant. Antidepressant use was associated with a significantly greater SBP and DBP drop at 5 minutes (\u3b2: 1.83, 0.16-3.50, P = 0.03 for SBP; \u3b2: 1.13, 0.02-2.25, P < 0.05 for DBP). Selective Serotonin Reuptake Inhibitor (SSRI) use was associated with a significantly greater likelihood of OH (OR 2.0, 1.1-3.6, P = 0.02). Both findings persisted following robust covariate adjustment. Conclusions: In older adults with AD, antidepressants were associated with a significantly greater SBP/DBP drop at 5 minutes. SSRI use in particular may be a risk factor for OH. This emphasises the need to screen older antidepressant users, and particularly those with AD, for ongoing orthostatic symptoms in order to reduce the risk of falls in this vulnerable cohort. This article is protected by copyright. All rights reserved