Chronic benzodiazepine suppresses translocator protein and elevates amyloid β in mice

Sabrina Tan, Daniel B. Metzger, Marianna E. Jung

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Benzodiazepine (BZD) is a commonly prescribed anxiolytic and sedation aid medication, especially in elderly women. However, long-term use of BZD provokes adverse nontherapeutic effects that include movement deficit. Here, we investigated motoric deficit and molecular changes in cerebellum associated with the chronic use of BZD (cBZD) in female mice. We measured neuroprotective translocator protein (TSPO), neurotoxic amyloid β (Aβ), Aβ-producing presenilin-1 (PS1), and Aβ-degrading neprilysin. We also tested whether cBZD treatment damages mitochondrial membranes by measuring mitochondrial membrane swelling and mitochondrial respiration. Young and old mice received BZD (lorazepam) for 20 days, were tested for motoric function using Rotarod, and then euthanized to collect cerebellum. The major methods were immunoblot and RT-PCR for TSPO, PS1, and neprilysin expressions; ELISA for Aβ level; spectrometry for mitochondrial membrane swelling; XF-respirometry for mitochondrial respiration. cBZD-treated old mice showed poorer motoric function than old control or young cBZD-treated mice. Old mice treated with cBZD showed a decrease in TSPO and neprilysin and an increase in Aβ and PS1 production compared to old control mice. Old cBZD-mice also showed an increase in mitochondrial membrane swelling and a decrease in mitochondrial respiration. These data suggest that cBZD exacerbates motoric aging in a manner that involves diminished TSPO, elevated Aβ and mitochondrial damage.

Original languageEnglish
Pages (from-to)59-67
Number of pages9
JournalPharmacology Biochemistry and Behavior
Volume172
DOIs
StatePublished - Sep 2018

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