Reduced Amygdala Microglial Expression of Brain-Derived Neurotrophic Factor and Tyrosine Kinase Receptor B (TrkB) in a Rat Model of Poststroke Depression.

Abstract

BACKGROUND Previous studies have implicated reduced brain-derived neurotrophic factor (BDNF) expression and BDNF-TrkB receptor signaling as well as microglial activation and neuroinflammation in poststroke depression (PSD). However, the contributions of microglial BDNF-TrkB signaling to PSD pathogenesis are unclear. MATERIAL AND METHODS We compared depression-like behaviors as well as neuronal and microglial BDNF and TrkB expression levels in the amygdala, a critical mood-relating limbic structure, in rat models of stroke, depression, and PSD. Depression-like behaviors were assessed using the sucrose preference test, open-field test, and weight measurements, while immunofluorescence double staining was employed to estimate BDNF and TrkB expression by CD11b-positive amygdala microglia and NeuN-positive amygdala neuron. Another group of PSD model rats were examined following daily intracerebroventricular injection of proBDNF, tissue plasminogen activator (t-PA), or normal saline (NS) for 7 days starting 4 weeks after chronic unpredictable mild stress (CUMS). RESULTS The numbers of BDNF/CD11b- and TrkB/CD11b-immunofluorescence-positive cells were lowest in the PSD group at 4 and 8 weeks after CUMS (P0.05). Injection of t-PA increased BDNF/CD11b- and TrkB/CD11b-positive cells in the amygdala of PSD rats and normalized behavior compared with NS or proBDNF injection (P<0.05). In contrast, proBDNF injection reduced BDNF and TrkB expression compared with NS (P<0.05). CONCLUSIONS These results suggest that decreased BDNF and TrkB expression by amygdala microglia may contribute to PSD pathogenesis and depression-like behaviors.

• Authors: Han-Xiao Zhu, Li-Jing Cheng, Ri-Wei Ou Yang, Yang-Yang Li, Jian Liu, Dan Dai, Wei Wang, Ning Yang, Yun Li
• Journal: Medical science monitor : international medical journal of experimental and clinical research (Med Sci Monit) Vol. 26 Pg. e926323 (Nov 18 2020) ISSN: 1643-3750 [Electronic] United States
• PMID: 33206632 (Publication Type: Journal Article)

Chemical References

• Brain-Derived Neurotrophic Factor
• CD11b Antigen
• Receptor, trkB
• Neuraminidase
• Tissue Plasminogen Activator

Topics

• Amygdala (metabolism)
• Animals
• Behavior, Animal
• Brain-Derived Neurotrophic Factor (metabolism)
• CD11b Antigen (metabolism)
• Depression (etiology, metabolism)
• Disease Models, Animal
• Injections, Intraventricular
• Microglia (metabolism)
• Motor Activity
• Neuraminidase (metabolism)
• Rats, Sprague-Dawley
• Receptor, trkB (metabolism)
• Stroke (complications)
• Tissue Plasminogen Activator (metabolism)