The long-term but not short-term use of benzodiazepine impairs motoric function and upregulates amyloid β in part through the suppression of translocator protein

Publication date: Available online 24 February 2020Source: Pharmacology Biochemistry and BehaviorAuthor(s): Marianna E. Jung, Daniel B. Metzger, James HallAbstractMany elderly American women use CNS depressant benzodiazepine (BZD) to ameliorate anxiety or insomnia. However, the chronic use of BZD (cBZD) is prevalent, causing adverse effects of BZD that include movement deficit. We previously reported that cBZD upregulates neurotoxic amyloid β42 (Aβ42) and downregulates neuroprotective translocator protein (TSPO) in the cerebellum, the brain area of movement and balance. The aim of the current study is two-fold: 1) to determine a direct effect of TSPO (inhibition) on cBZD-induced Aβ42 and Aβ-associated molecules; Aβ-producing-protein presenilin-1 (PS1) and Aβ-degrading-enzyme neprilysin and 2) to determine whether Aβ42 upregulation and motoric deficit occur upon a long-term (cBZD) rather than a short-term BZD (sBZD) treatment. Old female mice received BZD (lorazepam) for 20 days (cBZD) or 3 days (sBZD) with or without prototype TSPO ligand PK11195 and were tested for motoric performance for 3 days using Rotarod. ELISA was conducted to measure Aβ42 level and neprilysin activity in cerebellum. RT-PCR and immunoblot were conducted to measure the mRNA and protein levels of TSPO, PS1, and neprilysin. cBZD treatment decreased TSPO and neprilysin but increased Aβ42 accompanied by motoric deficit. Chronic PK11195 treatment acted as a TSPO inhibitor by suppressing TSPO e...
Source: Pharmacology Biochemistry and Behavior - Category: Biochemistry Source Type: research