PMID- 38178142
OWN - NLM
STAT- MEDLINE
DCOM- 20240108
LR  - 20240116
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 21
IP  - 1
DP  - 2024 Jan 4
TI  - Oxidative stress and inflammation cause auditory system damage via glial cell 
      activation and dysregulated expression of gap junction proteins in an 
      experimental model of styrene-induced oto/neurotoxicity.
PG  - 4
LID - 10.1186/s12974-023-02996-3 [doi]
LID - 4
AB  - BACKGROUND: Redox imbalance and inflammation have been proposed as the principal 
      mechanisms of damage in the auditory system, resulting in functional alterations 
      and hearing loss. Microglia and astrocytes play a crucial role in mediating 
      oxidative/inflammatory injury in the central nervous system; however, the role of 
      glial cells in the auditory damage is still elusive. OBJECTIVES: Here we 
      investigated glial-mediated responses to toxic injury in peripheral and central 
      structures of the auditory pathway, i.e., the cochlea and the auditory cortex 
      (ACx), in rats exposed to styrene, a volatile compound with well-known 
      oto/neurotoxic properties. METHODS: Male adult Wistar rats were treated with 
      styrene (400 mg/kg daily for 3 weeks, 5/days a week). Electrophysiological, 
      morphological, immunofluorescence and molecular analyses were performed in both 
      the cochlea and the ACx to evaluate the mechanisms underlying styrene-induced 
      oto/neurotoxicity in the auditory system. RESULTS: We showed that the 
      oto/neurotoxic insult induced by styrene increases oxidative stress in both 
      cochlea and ACx. This was associated with macrophages and glial cell activation, 
      increased expression of inflammatory markers (i.e., pro-inflammatory cytokines 
      and chemokine receptors) and alterations in connexin (Cxs) and pannexin (Panx) 
      expression, likely responsible for dysregulation of the microglia/astrocyte 
      network. Specifically, we found downregulation of Cx26 and Cx30 in the cochlea, 
      and high level of Cx43 and Panx1 in the ACx. CONCLUSIONS: Collectively, our 
      results provide novel evidence on the role of immune and glial cell activation in 
      the oxidative/inflammatory damage induced by styrene in the auditory system at 
      both peripheral and central levels, also involving alterations of gap junction 
      networks. Our data suggest that targeting glial cells and connexin/pannexin 
      expression might be useful to attenuate oxidative/inflammatory damage in the 
      auditory system.
CI  - (c) 2023. The Author(s).
FAU - Paciello, Fabiola
AU  - Paciello F
AD  - Department of Neuroscience, Universita Cattolica del Sacro Cuore, 00168, Rome, 
      Italy.
AD  - Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168, Rome, Italy.
FAU - Pisani, Anna
AU  - Pisani A
AD  - Department of Head and Neck Surgery, Universita Cattolica del Sacro Cuore, Rome, 
      Italy.
FAU - Rolesi, Rolando
AU  - Rolesi R
AD  - Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168, Rome, Italy.
AD  - Department of Head and Neck Surgery, Universita Cattolica del Sacro Cuore, Rome, 
      Italy.
FAU - Montuoro, Raffaele
AU  - Montuoro R
AD  - Department of Head and Neck Surgery, Universita Cattolica del Sacro Cuore, Rome, 
      Italy.
FAU - Mohamed-Hizam, Veronica
AU  - Mohamed-Hizam V
AD  - Department of Head and Neck Surgery, Universita Cattolica del Sacro Cuore, Rome, 
      Italy.
FAU - Boni, Giammarco
AU  - Boni G
AD  - Department of Neuroscience, Universita Cattolica del Sacro Cuore, 00168, Rome, 
      Italy.
FAU - Ripoli, Cristian
AU  - Ripoli C
AD  - Department of Neuroscience, Universita Cattolica del Sacro Cuore, 00168, Rome, 
      Italy.
AD  - Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168, Rome, Italy.
FAU - Galli, Jacopo
AU  - Galli J
AD  - Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168, Rome, Italy.
AD  - Department of Head and Neck Surgery, Universita Cattolica del Sacro Cuore, Rome, 
      Italy.
FAU - Sisto, Renata
AU  - Sisto R
AD  - Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, 
      Italian Workers' Compensation Authority (INAIL), Monte Porzio Catone, Rome, 
      Italy.
FAU - Fetoni, Anna Rita
AU  - Fetoni AR
AD  - Department of Neuroscience, Unit of Audiology, Universita Degli Studi di Napoli 
      Federico II, Naples, Italy. annarita.fetoni@unina.it.
FAU - Grassi, Claudio
AU  - Grassi C
AD  - Department of Neuroscience, Universita Cattolica del Sacro Cuore, 00168, Rome, 
      Italy.
AD  - Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168, Rome, Italy.
LA  - eng
PT  - Journal Article
DEP - 20240104
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
RN  - 0 (Connexins)
RN  - 44LJ2U959V (Styrene)
SB  - IM
MH  - Rats
MH  - Male
MH  - Animals
MH  - *Connexins/metabolism
MH  - *Styrene/toxicity/metabolism
MH  - Rats, Wistar
MH  - Gap Junctions/metabolism
MH  - Neuroglia/metabolism
MH  - Inflammation/chemically induced/metabolism
MH  - Oxidative Stress
MH  - Models, Theoretical
PMC - PMC10765700
OTO - NOTNLM
OT  - Astrogliosis
OT  - Auditory cortex
OT  - Cochlea
OT  - Gap junctions
OT  - Macrophages
OT  - Microglia morphology
OT  - Pro-inflammatory cytokines
OT  - ROS
COIS- The authors declare that they have no known competing financial interests or 
      personal relationships that could have appeared to influence the work reported in 
      this paper.
EDAT- 2024/01/05 00:43
MHDA- 2024/01/08 06:42
PMCR- 2024/01/04
CRDT- 2024/01/04 23:47
PHST- 2023/08/04 00:00 [received]
PHST- 2023/12/13 00:00 [accepted]
PHST- 2024/01/08 06:42 [medline]
PHST- 2024/01/05 00:43 [pubmed]
PHST- 2024/01/04 23:47 [entrez]
PHST- 2024/01/04 00:00 [pmc-release]
AID - 10.1186/s12974-023-02996-3 [pii]
AID - 2996 [pii]
AID - 10.1186/s12974-023-02996-3 [doi]
PST - epublish
SO  - J Neuroinflammation. 2024 Jan 4;21(1):4. doi: 10.1186/s12974-023-02996-3.