Accelerated long-term forgetting reveals everyday memory deficits in early-stage multiple sclerosis.

BACKGROUND: Patients with multiple sclerosis (MS) patients report subjective memory impairment (SMI) escaping routine neuropsychological testing. Accelerated long-term forgetting (ALF) refers to above average loss of information over an extended period of time (e.g., 7 days). This study investigates ALF in mildly affected MS patients and relates long-term memory performance to SMI. METHODS: This prospective study included 30 patients with early MS (mean EDSS ± SD = 1.1 ± 0.9) and 30 healthy controls (HC) matched for age and education. Participants underwent ALF testing [word list (RAVLT), geometric figure (RCF), logical memory (WMS)] at three time points (baseline, 30 min, 7 days). Cognition (Montreal Cognitive Assessment), depression, SMI and fatigue were assessed. The primary outcome (PO) was defined as the quotient of the 7-day score and the 30-min memory score for the verbal (RAVLT, WMS) and figural (RCF) memory tests. The study was approved by the local ethics committee and is registered in the German Register of Clinical Studies (DRKS00025791). RESULTS: MS patients showed impairments in PORAVLT (MS 0.66 ± 0.13 vs HC 0.82 ± 0.16; p < 0.001), whereas POWMS (MS 0.88 ± 0.15 vs HC 1.01 ± 0.12; p = 0.02) showed only a tendency. Regression analysis revealed significant associations for PORAVLT and fatigue (p = 0.034), and PORAVLT and SMI (p = 0.01) in patients but not in HC. CONCLUSION: The ALF test quantifies SMI in MS-patients. With fatigue as a relevant associated factor, this fills the gap in objectifying SMI in MS for diagnostic purposes.

Characterization of the pharmacology, signal transduction and internalization of the fluorescent PACAP ligand, fluor-PACAP, on NIH/3T3 cells expressing PAC1.

Fluor-PACAP, a fluorescent derivative of PACAP-27, has been confirmed to share a high affinity for PAC1 receptors transfected into NIH/3T3 cells and to have comparable pharmacological characteristics to the unconjugated, native form. Through competitive binding with 125I-PACAP-27, the two ligands exhibited similar dose- dependent inhibition. Additional examination of the efficacy of activating adenylyl cyclase revealed that both ligands analogously stimulated the production of cyclic AMP. Furthermore, PAC1 internalization visualized by our Fluor-PACAP, is compareable to that performed with the radioligand, 125I-PACAP-27, with maximal internalization achieved within thirty minutes. Thus, Fluor-PACAP exhibits intracellular signaling abilities homologous to the native ligand.