TY - JOUR
T1 - Chronic benzodiazepine suppresses translocator protein and elevates amyloid β in mice
AU - Tan, Sabrina
AU - Metzger, Daniel B.
AU - Jung, Marianna E.
N1 - Funding Information:
This study was supported by the National Institutes of Health /National Institutes on Aging grant ( AG053974 ).
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/9
Y1 - 2018/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85050550118&partnerID=8YFLogxK
U2 - 10.1016/j.pbb.2018.07.005
DO - 10.1016/j.pbb.2018.07.005
M3 - Article
C2 - 30030126
AN - SCOPUS:85050550118
SN - 0091-3057
VL - 172
SP - 59
EP - 67
JO - Pharmacology, Biochemistry and Behavior
JF - Pharmacology, Biochemistry and Behavior
ER -