Chronic stress exacerbates neuronal loss associated with secondary neurodegeneration and suppresses microglial-like cells following focal motor cortex ischemia in the mouse.
Post-stroke patients describe suffering from persistent and unremitting levels of distress. Using an experimental model of focal cortical ischemia in adult male C57BL/6 mice, we examined whether exposure to chronic stress could modify the development of secondary thalamic neurodegeneration (STND), which is commonly reported to be associated with impaired functional recovery. We were particularly focused on the modulatory role of microglia-like cells, as several clinical studies have linked microglial activation to the development of STND. One month following the induction of cortical ischemia we identified that numbers of microglial-like cells, as well as putative markers of microglial structural reorganization (Iba-1), complement processing (CD11b), phagocytosis (CD68), and antigen presentation (MHC-II) were all significantly elevated in response to occlusion. We further identified that these changes co-occurred with a decrease in the numbers of mature neurons within the thalamus. Occluded animals that were also exposed to chronic stress exhibited significantly lower levels of Iba-1 positive cells and a reduced expression of Iba-1 and CD11b compared to the 'occlusion-alone' group. Interestingly, the dampened expression of microglial/monocyte markers observed in stressed animals was associated with significant additional loss of neurons. These findings indicate that the process of STND can be negatively modified, potentially in a microglial dependent manner, by exposure to chronic stress.
School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia; Centre for Translational Neuroscience and Mental Health Research, Australia; Hunter Medical Research Institute, Newcastle, NSW, Australia.
Kimberley A
KA
Jones
School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia; Centre for Translational Neuroscience and Mental Health Research, Australia; Hunter Medical Research Institute, Newcastle, NSW, Australia.
Ihssane
I
Zouikr
School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia; Centre for Translational Neuroscience and Mental Health Research, Australia; Hunter Medical Research Institute, Newcastle, NSW, Australia.
Madeleine
M
Patience
Department of Anatomy and the Brain Health Research Center, Dunedin 9054, New Zealand; Centre for Translational Physiology, University of Otago Wellington, Dunedin 9054, New Zealand; Department of Psychology, University of Otago, Dunedin 9054, New Zealand.
Andrew N
AN
Clarkson
University of Newcastle, Australia; Laboratory of Experimental Endocrinology, Department of Internal Medicine, Sahlgrenska Academy at the University of Gothenburg, SE-413 45 Gothenburg, Sweden.
Jörgen
J
Isgaard
School of Electrical Engineering and Computer Science, University of Newcastle, Callaghan, NSW, Australia.
Sarah J
SJ
Johnson
School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia; Centre for Translational Neuroscience and Mental Health Research, Australia; Hunter Medical Research Institute, Newcastle, NSW, Australia.
Neil
N
Spratt
University of Newcastle, Australia; Hunter Medical Research Institute, Newcastle, NSW, Australia.
Michael
M
Nilsson
School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia; Centre for Translational Neuroscience and Mental Health Research, Australia; Hunter Medical Research Institute, Newcastle, NSW, Australia. Electronic address: rohan.walker@newcastle.edu.au.
Frederick R
FR
Walker
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology*; D039481:CD11b Antigen / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002452:Cell Count; D004195:Disease Models, Animal; D005802:Genes, MHC Class II; D008262:Macrophage Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000378:metabolism / Q000473:pathology*; D009044:Motor Cortex / Q000378:metabolism / Q000473:pathology*; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D020127:Recovery of Function / Q000502:physiology; D013312:Stress, Physiological / Q000502:physiology*; D013315:Stress, Psychological / Q000378:metabolism / Q000473:pathology*; D013788:Thalamus / Q000378:metabolism / Q000473:pathology*; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D039481:CD11b Antigen; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; C491049:Aif1 protein, mouse; C067980:CD68 antigen, human; D000097382:CD68 Molecule
Chronic stress; Microglia; Secondary neurodegeneration; Stroke; Thalamus