BDNF Driven Coupling Between KCC2 Downregulation and Fyn-Dependent Phosphorylation of GluN2B NMDA Receptors in Human Spinal Pain Processing

It appears your Web browser is not configured to display PDF files. Download adobe Acrobat or click here to download the PDF file.

Click here to download the PDF file.

Creator: 

Kandegedara, Chaya

Date: 

2019

Abstract: 

Hyperexcitation of neurons in the dorsal horn of the spinal cord leads to chronic pain. In rodent pain models, the neurotrophic factor BDNF mediates loss of inhibitory signalling. This permits enhancement of excitatory GluN2B-NMDAR currents in lamina I neuronal synapses. However, whether this pathway is conserved between rodents and humans as well as between sexes is unknown. We developed a human ex vivo BDNF model of pathological pain using postmortem human spinal tissue. We found that ex vivo BDNF downregulates KCC2 and active STEP61 and upregulates active Fyn and phosphorylated GluN2B at the superficial dorsal horn in both human and rodent males. We also show that BDNF increases intracellular KCC2 of superficial dorsal horn neurons. Thus, our human model may connect the vast translational divide between rodent and human chronic pain mechanisms to identify and validate new therapeutic targets for human chronic pain.

Subject: 

Neuroscience

Language: 

English

Publisher: 

Carleton University

Thesis Degree Name: 

Master of Science: 
M.Sc.

Thesis Degree Level: 

Master's

Thesis Degree Discipline: 

Neuroscience

Parent Collection: 

Theses and Dissertations

Items in CURVE are protected by copyright, with all rights reserved, unless otherwise indicated. They are made available with permission from the author(s).