PMID- 31939008
OWN - NLM
STAT- MEDLINE
DCOM- 20210122
LR  - 20240329
IS  - 1573-6830 (Electronic)
IS  - 0272-4340 (Print)
IS  - 0272-4340 (Linking)
VI  - 40
IP  - 6
DP  - 2020 Aug
TI  - Unraveling the Role of Astrocytes in Subthalamic Nucleus Deep Brain Stimulation 
      in a Parkinson's Disease Rat Model.
PG  - 939-954
LID - 10.1007/s10571-019-00784-3 [doi]
AB  - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective 
      therapeutic strategy for motor symptoms of Parkinson's disease (PD) when L-DOPA 
      therapy induces disabling side effects. Classical inflammatory activation of 
      glial cells is well established in PD, contributing to the progressive 
      neurodegenerative state; however, the role of DBS in regulating the inflammatory 
      response remains largely unknown. To understand the involvement of astrocytes in 
      the mechanisms of action of DBS, we evaluated the effect of STN-DBS in regulating 
      motor symptoms, astrocyte reactivity, and cytokine expression in a 6-OHDA-induced 
      PD rat model. To mimic in vivo DBS, we investigate the effect of high-frequency 
      stimulation (HFS) in cultured astrocytes regulating cytokine induction and NF-kappaB 
      activation. We found that STN-DBS improved motor impairment, induced astrocytic 
      hyperplasia, and reversed increased IFN-gamma and IL-10 levels in the globus pallidus 
      (GP) of lesioned rats. Moreover, HFS activated astrocytes and prevented 
      TNF-alpha-induced increase of monocyte chemoattractant protein-1 (MCP-1) and NF-kappaB 
      activation in vitro. Our results indicate that DBS/HFS may act as a regulator of 
      the inflammatory response in PD states, attenuating classical activation of 
      astrocytes and cytokine induction, potentially through its ability to regulate 
      NF-kappaB activation. These findings may help us understand the role of astrocyte 
      signaling in HFS, highlighting its possible relationship with the effectiveness 
      of DBS in neurodegenerative disorders.
FAU - Campos, Ana Carolina Pinheiro
AU  - Campos ACP
AD  - Division of Neuroscience, Hospital Sirio-Libanes, Sao Paulo, SP, 01308-060, 
      Brazil.
FAU - Kikuchi, Daniel Seicho
AU  - Kikuchi DS
AD  - Department of Medicine, Emory University, Atlanta, GA, 30322, USA.
FAU - Paschoa, Amanda Faure Nardini
AU  - Paschoa AFN
AD  - Division of Neuroscience, Hospital Sirio-Libanes, Sao Paulo, SP, 01308-060, 
      Brazil.
FAU - Kuroki, Mayra Akemi
AU  - Kuroki MA
AD  - Division of Neuroscience, Hospital Sirio-Libanes, Sao Paulo, SP, 01308-060, 
      Brazil.
FAU - Fonoff, Erich Talamoni
AU  - Fonoff ET
AD  - Division of Neurosurgery, Department of Neurology, University of Sao Paulo 
      Medical School, Sao Paulo, 01246-903, Brazil.
FAU - Hamani, Clement
AU  - Hamani C
AD  - Sunnybrook Health Research Institute, Harquail Centre for Neuromodulation, 
      Toronto, ON, M4N 3M5, Canada.
FAU - Pagano, Rosana Lima
AU  - Pagano RL
AUID- ORCID: 0000-0002-5351-6575
AD  - Division of Neuroscience, Hospital Sirio-Libanes, Sao Paulo, SP, 01308-060, 
      Brazil. rosana.lpagano@hsl.org.br.
FAU - Hernandes, Marina Sorrentino
AU  - Hernandes MS
AD  - Department of Medicine, Emory University, Atlanta, GA, 30322, USA.
LA  - eng
GR  - 2016/07168-2/Sao Paulo Research Foundation/
GR  - 2017/14020-4/Sao Paulo Research Foundation/
GR  - 17SDG33410777/American Heart Association/
PT  - Journal Article
DEP - 20200114
PL  - United States
TA  - Cell Mol Neurobiol
JT  - Cellular and molecular neurobiology
JID - 8200709
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Astrocytes/*pathology
MH  - *Deep Brain Stimulation
MH  - Disease Models, Animal
MH  - Electric Stimulation
MH  - Globus Pallidus/pathology
MH  - Hyperplasia
MH  - Inflammation/pathology
MH  - Male
MH  - Mice
MH  - Motor Activity
MH  - NF-kappa B/metabolism
MH  - Parkinson Disease/*pathology
MH  - Rats, Wistar
MH  - Signal Transduction
MH  - Subthalamic Nucleus/*pathology
MH  - Tumor Necrosis Factor-alpha/pharmacology
PMC - PMC7295825
OTO - NOTNLM
OT  - Astrocytes
OT  - Deep brain stimulation
OT  - High-frequency stimulation
OT  - Inflammation
OT  - NF-kappaB
OT  - Parkinson's disease
COIS- The authors declare that they have no competing interests.
EDAT- 2020/01/16 06:00
MHDA- 2021/01/23 06:00
PMCR- 2020/01/14
CRDT- 2020/01/16 06:00
PHST- 2019/10/15 00:00 [received]
PHST- 2019/12/31 00:00 [accepted]
PHST- 2020/01/16 06:00 [pubmed]
PHST- 2021/01/23 06:00 [medline]
PHST- 2020/01/16 06:00 [entrez]
PHST- 2020/01/14 00:00 [pmc-release]
AID - 10.1007/s10571-019-00784-3 [pii]
AID - 784 [pii]
AID - 10.1007/s10571-019-00784-3 [doi]
PST - ppublish
SO  - Cell Mol Neurobiol. 2020 Aug;40(6):939-954. doi: 10.1007/s10571-019-00784-3. Epub 
      2020 Jan 14.