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Sex-Dependent Affective and Cognitive Outcomes of Spinal Cord Injury: The Role of the Hippocampus and Effects of Systemically Administered Insulin-Like Growth Factor 1
Abstract
Depression and cognitive deficits among people with spinal cord injury (SCI) present at higher rates compared to the general population, yet these SCI comorbidities are poorly addressed. Sex and age appear to play roles in depression incidence, but consensus on the direction of their effects is limited. Systemic and cortical inflammation and disruptions in hippocampal neurogenesis have been identified as potential treatment targets, but a comprehensive understanding of these mechanisms remains elusive.
Presently, I used a rodent SCI model to interrogate previously identified post-injury depression-like behavior and cognitive deficits, in young and middle-aged male and female subjects, and their association through hippocampal neurogenesis. I investigated chronic systemic and hippocampal inflammation and their effects on hippocampal neurogenesis, affect, and cognition. Depression-like behavior manifested in male and female subsets of SCI rats irrespective of age, at rates commensurate with clinical depression incidence. Changes in components of behavior were driven by sex and age, and affective outcomes were independent of common postinjury pathophysiological outcomes including locomotor functional deficits and spinal lesion severity. However, only male depression-like SCI rats exhibited deficits in hippocampal associated spatial cognition and in hippocampal neurogenesis, which coincided with increases in neuroinflammation among middle-aged subjects.
I attempted to address these disruptions in affect, cognition, and neurogenesis with i.p. administration of IGF-1 within 24 hours of injury. IGF-1 administered i.c.v. has shown promise in recovering affect and cognition in SCI subjects. Although i.p. IGF-1 did not attenuate the manifestation of depression-like behavior in a subset of SCI rats or improve hippocampal neurogenesis responsible for affect, depression-like SCI subjects did exhibit cognitive function similar to non-depression-like SCI rats and improved hippocampal neurogenesis driving aspects of cognitive function. IGF-1 also robustly improved locomotor and weight recovery after injury, highlighting the pleiotropic effects of systemically administered IGF-1.
Overall, the present data suggest that post-SCI depression and cognition may in part be sex-differentially associated by hippocampal neurogenic and inflammatory processes, and that growth factors, administered judiciously, may play a beneficial role in the context of therapeutic strategies addressing psychological wellbeing after SCI.
Subject
Spinal cord injurydepression
cognition
neurogenesis
inflammation
insulin-like growth factor 1
Collections
Citation
Stefanov, Alexander V. (2023). Sex-Dependent Affective and Cognitive Outcomes of Spinal Cord Injury: The Role of the Hippocampus and Effects of Systemically Administered Insulin-Like Growth Factor 1. Doctoral dissertation, Texas A&M University. Available electronically from https : / /hdl .handle .net /1969 .1 /203054.