PMID- 28806500
OWN - NLM
STAT- MEDLINE
DCOM- 20180619
LR  - 20180620
IS  - 1932-8494 (Electronic)
IS  - 1932-8486 (Linking)
VI  - 300
IP  - 12
DP  - 2017 Dec
TI  - Doxepin Mitigates Noise-induced Neuronal Damage in Primary Auditory Cortex of 
      Mice via Suppression of Acid Sphingomyelinase/Ceramide Pathway.
PG  - 2220-2232
LID - 10.1002/ar.23677 [doi]
AB  - Neuronal damage in primary auditory cortex (A1) underlies complex manifestations 
      of noise exposure, prevention of which is critical for health maintenance. Acid 
      sphingomyelinase (ASM) catalyzes generation of ceramide (Cer) which if 
      over-activated mediates neuronal disorders in various diseases. Tricyclic 
      antidepressants (TCAs), by restraining ASM/Cer, benefits multiple neuronal 
      anomalies, so we aimed to elucidate the effect of TCA on noise induced hearing 
      loss and auditory cortex derangement, unraveling mechanism involved. The mice 
      were exposed to noise with frequencies of 20-20 KHz and intensity of 95 dB. 
      Doxepin hydrochloride (DOX), a kind of TCAs, was given intragastrically by 5 
      mg kg(-1)  days(-1) . Morphology of neurons was examined using hematoxylin-eosin 
      (HE) and Nissl staining. Apoptosis was assayed through transferase-mediated dUTP 
      nick end labeling (TUNEL). The content of ASM, Cer or acid ceramidase (AC) was 
      detected by western blot and immunohistochemistry analysis. We demonstrated 
      intense, broad band noise caused upward shift of auditory brainstem response 
      (ABR) threshold to sound over frequencies 4-32 KHz, with prominent morphologic 
      changes and enhanced apoptosis in neurons of primary auditory cortex (A1) 
      (P < 0.05). DOX partly restored noise-caused hearing loss alleviating morphologic 
      changes or apoptosis remarkably (P < 0.05). Both ASM and Cer abundance were 
      elevated significantly by noise which was reversed upon DOX treatment (P < 0.05), 
      but neither noise nor DOX altered AC content. DOX had no influence on hearing, 
      neuronal morphology or ASM/Cer in control mice. Our result suggests DOX palliates 
      noise induced hearing loss and neuronal damage in auditory cortex by correcting 
      over-activation of ASM/Cer without hampering intrinsic behavior of it. Anat Rec, 
      300:2220-2232, 2017. (c) 2017 Wiley Periodicals, Inc.
CI  - (c) 2017 Wiley Periodicals, Inc.
FAU - Su, Yu-Ting
AU  - Su YT
AD  - Department of Aerospace Hygiene, Fourth Military Medical University, Xi'an 
      710032, People's Republic of China.
FAU - Meng, Xing-Xing
AU  - Meng XX
AD  - Department of Aerospace Hygiene, Fourth Military Medical University, Xi'an 
      710032, People's Republic of China.
FAU - Zhang, Xi
AU  - Zhang X
AD  - Department of Aerospace Hygiene, Fourth Military Medical University, Xi'an 
      710032, People's Republic of China.
FAU - Guo, Yi-Bin
AU  - Guo YB
AD  - Department of Aerospace Hygiene, Fourth Military Medical University, Xi'an 
      710032, People's Republic of China.
FAU - Zhang, Hai-Jun
AU  - Zhang HJ
AD  - Department of Aerospace Hygiene, Fourth Military Medical University, Xi'an 
      710032, People's Republic of China.
FAU - Cheng, Yao-Ping
AU  - Cheng YP
AD  - Department of Aerospace Hygiene, Fourth Military Medical University, Xi'an 
      710032, People's Republic of China.
FAU - Xie, Xiao-Ping
AU  - Xie XP
AD  - Department of Aerospace Hygiene, Fourth Military Medical University, Xi'an 
      710032, People's Republic of China.
FAU - Chang, Yao-Ming
AU  - Chang YM
AD  - Department of Aerospace Hygiene, Fourth Military Medical University, Xi'an 
      710032, People's Republic of China.
FAU - Bao, Jun-Xiang
AU  - Bao JX
AUID- ORCID: 0000-0001-5805-0543
AD  - Department of Aerospace Hygiene, Fourth Military Medical University, Xi'an 
      710032, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20170828
PL  - United States
TA  - Anat Rec (Hoboken)
JT  - Anatomical record (Hoboken, N.J. : 2007)
JID - 101292775
RN  - 0 (Antidepressive Agents, Tricyclic)
RN  - 0 (Ceramides)
RN  - 1668-19-5 (Doxepin)
RN  - EC 3.1.4.12 (Sphingomyelin Phosphodiesterase)
SB  - IM
MH  - Acoustic Stimulation/adverse effects
MH  - Animals
MH  - Antidepressive Agents, Tricyclic/pharmacology/therapeutic use
MH  - Auditory Cortex/drug effects/*metabolism/pathology
MH  - Ceramides/antagonists & inhibitors/*metabolism
MH  - Doxepin/*pharmacology/therapeutic use
MH  - Hearing Loss, Noise-Induced/drug therapy/*metabolism/pathology
MH  - Male
MH  - Mice
MH  - Neurons/drug effects/metabolism/pathology
MH  - Noise/*adverse effects
MH  - Signal Transduction/drug effects/physiology
MH  - Sphingomyelin Phosphodiesterase/antagonists & inhibitors/*metabolism
OTO - NOTNLM
OT  - acid sphingomyelinase
OT  - apoptosis
OT  - ceramide
OT  - noise
OT  - primary auditory cortex
EDAT- 2017/08/15 06:00
MHDA- 2018/06/21 06:00
CRDT- 2017/08/15 06:00
PHST- 2017/03/12 00:00 [received]
PHST- 2017/06/15 00:00 [revised]
PHST- 2017/06/26 00:00 [accepted]
PHST- 2017/08/15 06:00 [pubmed]
PHST- 2018/06/21 06:00 [medline]
PHST- 2017/08/15 06:00 [entrez]
AID - 10.1002/ar.23677 [doi]
PST - ppublish
SO  - Anat Rec (Hoboken). 2017 Dec;300(12):2220-2232. doi: 10.1002/ar.23677. Epub 2017 
      Aug 28.