PMID- 31130845
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1662-5102 (Print)
IS  - 1662-5102 (Electronic)
IS  - 1662-5102 (Linking)
VI  - 13
DP  - 2019
TI  - 5-HT1A Receptor Agonist Promotes Retinal Ganglion Cell Function by Inhibiting 
      OFF-Type Presynaptic Glutamatergic Activity in a Chronic Glaucoma Model.
PG  - 167
LID - 10.3389/fncel.2019.00167 [doi]
LID - 167
AB  - Serotonin receptors are potential neuroprotective agents in degenerative diseases 
      of the central nervous system. The protective effects of serotonin receptor 
      (5-HT1A) agonists on the survival and function of retinal ganglion cells (RGCs) 
      by regulating the release of the presynaptic neurotransmitter gamma-aminobutyric acid 
      (GABA) were confirmed in our previous study of a chronic glaucoma rat model. 
      However, the roles of excitatory amino acids and their interactions with the 
      5-HT1A receptor in glaucoma remain unknown. Here, we found that ocular 
      hypertension increased glutamine synthetase (GS) and excitatory amino acid 
      transporter 2 (EAAT2) expression in rat retinas. In addition, the high expression 
      of GS and EAAT2 induced by glaucoma was downregulated by the 5-HT1A receptor 
      agonist 8-OH-DPAT and the 5-HT1A receptor antagonist WAY-100635, respectively. 
      Patch-clamp techniques were used to record glutamate receptor-mediated 
      spontaneous and miniature glutamatergic excitatory post-synaptic currents (sEPSCs 
      and mEPSCs) as well as L-glutamate-induced current in OFF-type and ON-type RGCs 
      in rat retinal slices. Although there were no significant differences in the 
      frequency and amplitude of sEPSC and mEPSC release between normal and glaucoma 
      OFF- and ON-type RGCs, exogenous 8-OH-DPAT administration specifically reduced 
      the frequency, but not the amplitude, of sEPSC and mEPSC release in glaucoma 
      OFF-type rather than ON-type RGCs; these effects were completely blocked by 
      WAY-100635. In summary, 8-OH-DPAT decreases and increases GS and EAAT2 expression 
      of glaucomatous retina, respectively, while decreasing sEPSC and mEPSC frequency. 
      In contrast, WAY-100635 increases and decreases GS and EAAT2 expression of 
      glaucomatous retina, respectively, while increasing sEPSC and mEPSC frequency. 
      The reduction of glutamatergic presynaptic transmission by 8-OH-DPAT deactivates 
      RGCs at the neural network level and reduces the excitotoxic damage in the 
      pathological process of chronic glaucoma.
FAU - Zhou, Xujiao
AU  - Zhou X
AD  - Eye Institute, Eye and ENT Hospital, State Key Laboratory of Medical 
      Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for 
      Brain Science, Shanghai Medical College, Fudan University, Shanghai, China.
AD  - Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China.
AD  - NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, 
      Chinese Academy of Medical Sciences (Fudan University), Shanghai, China.
FAU - Li, Gang
AU  - Li G
AD  - Eye Institute, Eye and ENT Hospital, State Key Laboratory of Medical 
      Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for 
      Brain Science, Shanghai Medical College, Fudan University, Shanghai, China.
AD  - Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China.
AD  - NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, 
      Chinese Academy of Medical Sciences (Fudan University), Shanghai, China.
FAU - Zhang, Shenghai
AU  - Zhang S
AD  - Eye Institute, Eye and ENT Hospital, State Key Laboratory of Medical 
      Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for 
      Brain Science, Shanghai Medical College, Fudan University, Shanghai, China.
AD  - Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China.
AD  - NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, 
      Chinese Academy of Medical Sciences (Fudan University), Shanghai, China.
FAU - Wu, Jihong
AU  - Wu J
AD  - Eye Institute, Eye and ENT Hospital, State Key Laboratory of Medical 
      Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for 
      Brain Science, Shanghai Medical College, Fudan University, Shanghai, China.
AD  - Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China.
AD  - NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, 
      Chinese Academy of Medical Sciences (Fudan University), Shanghai, China.
AD  - Department of Ophthalmology and Vision Science, Eye and ENT Hospital, Fudan 
      University, Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20190503
PL  - Switzerland
TA  - Front Cell Neurosci
JT  - Frontiers in cellular neuroscience
JID - 101477935
PMC - PMC6509153
OTO - NOTNLM
OT  - 5-HT1A receptor
OT  - OFF-type RGCs
OT  - glaucoma
OT  - glutamate release
OT  - neuroprotection
EDAT- 2019/05/28 06:00
MHDA- 2019/05/28 06:01
PMCR- 2019/01/01
CRDT- 2019/05/28 06:00
PHST- 2019/01/17 00:00 [received]
PHST- 2019/04/08 00:00 [accepted]
PHST- 2019/05/28 06:00 [entrez]
PHST- 2019/05/28 06:00 [pubmed]
PHST- 2019/05/28 06:01 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fncel.2019.00167 [doi]
PST - epublish
SO  - Front Cell Neurosci. 2019 May 3;13:167. doi: 10.3389/fncel.2019.00167. 
      eCollection 2019.