scholarly journals Abnormal Ca2+ Signals in Reactive Astrocytes as a Common Cause of Brain Diseases

2021 ◽  
Vol 23 (1) ◽  
pp. 149
Author(s):  
Schuichi Koizumi ◽  
Eiji Shigetomi ◽  
Fumikazu Sano ◽  
Kozo Saito ◽  
Sun Kwang Kim ◽  
...  

In pathological brain conditions, glial cells become reactive and show a variety of responses. We examined Ca2+ signals in pathological brains and found that reactive astrocytes share abnormal Ca2+ signals, even in different types of diseases. In a neuropathic pain model, astrocytes in the primary sensory cortex became reactive and showed frequent Ca2+ signals, resulting in the production of synaptogenic molecules, which led to misconnections of tactile and pain networks in the sensory cortex, thus causing neuropathic pain. In an epileptogenic model, hippocampal astrocytes also became reactive and showed frequent Ca2+ signals. In an Alexander disease (AxD) model, hGFAP-R239H knock-in mice showed accumulation of Rosenthal fibers, a typical pathological marker of AxD, and excessively large Ca2+ signals. Because the abnormal astrocytic Ca2+ signals observed in the above three disease models are dependent on type II inositol 1,4,5-trisphosphate receptors (IP3RII), we reanalyzed these pathological events using IP3RII-deficient mice and found that all abnormal Ca2+ signals and pathologies were markedly reduced. These findings indicate that abnormal Ca2+ signaling is not only a consequence but may also be greatly involved in the cause of these diseases. Abnormal Ca2+ signals in reactive astrocytes may represent an underlying pathology common to multiple diseases.

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Yan Dong ◽  
Chong-Yang Li ◽  
Xiao-Min Zhang ◽  
Ya-Nan Liu ◽  
Shuang Yang ◽  
...  

AbstractOur previous research has shown that galanin plays an antinociceptive effect via binding to galanin receptors (GalRs) in nucleus accumbens (NAc). This study focused on the involvement of GalR2 in galanin-induced antinociceptive effect in NAc of neuropathic pain rats. The chronic constriction injury of sciatic nerve (CCI) was used to mimic neuropathic pain model. The hind paw withdrawal latency (HWL) to thermal stimulation and hind paw withdrawal threshold (HWT) to mechanical stimulation were measured as the indicators of pain threshold. The results showed that 14 and 28 days after CCI, the expression of GalR2 was up-regulated in bilateral NAc of rats, and intra-NAc injection of GalR2 antagonist M871 reversed galanin-induced increases in HWL and HWT of CCI rats. Furthermore, intra-NAc injection of GalR2 agonist M1145 induced increases in HWL and HWT at day 14 and day 28 after CCI, which could also be reversed by M871. Finally, we found that M1145-induced antinociceptive effect in NAc of CCI rats was stronger than that in intact rats. These results imply that the GalR2 is activated in the NAc from day 14 to day 28 after CCI and GalR2 is involved in the galanin-induced antinociceptive effect in NAc of CCI rats.


2021 ◽  
Vol 22 (5) ◽  
pp. 2479
Author(s):  
Amir Mohammadzadeh ◽  
Péter P. Lakatos ◽  
Mihály Balogh ◽  
Ferenc Zádor ◽  
Dávid Árpád Karádi ◽  
...  

The limited effect of current medications on neuropathic pain (NP) has initiated large efforts to develop effective treatments. Animal studies showed that glycine transporter (GlyT) inhibitors are promising analgesics in NP, though concerns regarding adverse effects were raised. We aimed to study NFPS and Org-25543, GlyT-1 and GlyT-2 inhibitors, respectively and their combination in rat mononeuropathic pain evoked by partial sciatic nerve ligation. Cerebrospinal fluid (CSF) glycine content was also determined by capillary electrophoresis. Subcutaneous (s.c.) 4 mg/kg NFPS or Org-25543 showed analgesia following acute administration (30–60 min). Small doses of each compound failed to produce antiallodynia up to 180 min after the acute administration. However, NFPS (1 mg/kg) produced antiallodynia after four days of treatment. Co-treatment with subanalgesic doses of NFPS (1 mg/kg) and Org-25543 (2 mg/kg) produced analgesia at 60 min and thereafter meanwhile increased significantly the CSF glycine content. This combination alleviated NP without affecting motor function. Test compounds failed to activate G-proteins in spinal cord. To the best of our knowledge for the first time we demonstrated augmented analgesia by combining GlyT-1 and 2 inhibitors. Increased CSF glycine content supports involvement of glycinergic system. Combining selective GlyT inhibitors or developing non-selective GlyT inhibitors might have therapeutic value in NP.


Neuroreport ◽  
2008 ◽  
Vol 19 (8) ◽  
pp. 825-829 ◽  
Author(s):  
Richard Hulse ◽  
David Wynick ◽  
Lucy F. Donaldson

2018 ◽  
Vol 97 ◽  
pp. 870-879 ◽  
Author(s):  
Carlos Demócedes Luís de França Almeida Moreira ◽  
Jonas Gabriel de Oliveira Pinheiro ◽  
Walter Ferreira da Silva-Júnior ◽  
Euzébio Guimarães Barbosa ◽  
Zênia Maria Maciel Lavra ◽  
...  

Pain ◽  
2017 ◽  
Vol 158 (12) ◽  
pp. 2452-2460 ◽  
Author(s):  
Sherelle L. Casey ◽  
Nicholas Atwal ◽  
Christopher W. Vaughan

Sign in / Sign up

Export Citation Format

Share Document