Microglial cell hyper-ramification and neuronal dendritic spine loss in the hippocampus and medial prefrontal cortex in a mouse model of PTSD
| Autor: | David J. Clarke, Mustafa S. Kassem, Miguel A. Bedoya-Pérez, Jonathon C. Arnold, Michael Kuligowski, Stephanie M. Todd, Max R. Bennett, Jim Lagopoulos, Kristie Leigh Smith |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Reflex Startle Dendritic spine Dendritic Spines Immunology Hippocampus Prefrontal Cortex Grey matter Biology Amygdala Stress Disorders Post-Traumatic 03 medical and health sciences Behavioral Neuroscience Mice 0302 clinical medicine medicine Animals Prefrontal cortex Neuroinflammation Neurons Microglia Endocrine and Autonomic Systems Pyramidal Cells Brain Fear Temporal Lobe Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure Facilitation Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Brain, behavior, and immunity. 80 |
| ISSN: | 1090-2139 |
| Popis: | Few animal models exist that successfully reproduce several core associative and non-associative behaviours relevant to post-traumatic stress disorder (PTSD), such as long-lasting fear reactions, hyperarousal, and subtle attentional and cognitive dysfunction. As such, these models may lack the face validity required to adequately model pathophysiological features of PTSD such as CNS grey matter loss and neuroinflammation. Here we aimed to investigate in a mouse model of PTSD whether contextual fear conditioning associated with a relatively high intensity footshock exposure induces loss of neuronal dendritic spines in various corticolimbic brain regions, as their regression may help explain grey matter reductions in PTSD patients. Further, we aimed to observe whether these changes were accompanied by alterations in microglial cell number and morphology, and increased expression of complement factors implicated in the mediation of microglial cell-mediated engulfment of dendritic spines. Adult male C57Bl6J mice were exposed to a single electric footshock and subsequently underwent phenotyping of various PTSD-relevant behaviours in the short (day 2-4) and longer-term (day 29-31). 32 days post-exposure the brains of these animals were subjected to Golgi staining of dendritic spines, microglial cell Iba-1 immunohistochemistry and immunofluorescent staining of the complement factors C1q and C4. Shock exposure promoted a lasting contextual fear response, decreased locomotor activity, exaggerated acoustic startle responses indicative of hyperarousal, and a short-term facilitation of sensorimotor gating function. The shock triggered loss of dendritic spines on pyramidal neurons was accompanied by increased microglial cell number and complexity in the medial prefrontal cortex and dorsal hippocampus, but not in the amygdala. Shock also increased expression of C1q in the pyramidal layer of the CA1 region of the hippocampus but not in other brain regions. The present study further elaborates on the face and construct validity of a mouse model of PTSD and provides a good foundation to explore potential molecular interactions between microglia and dendritic spines. |
| Databáze: | OpenAIRE |
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