TY - JOUR
T1 - Traumatic brain injury alters the effects of class II invariant peptide (CLIP) antagonism on chronic meningeal CLIP + B cells, neuropathology, and neurobehavioral impairment in 5xFAD mice
AU - Iannucci, Jaclyn
AU - Dominy, Reagan
AU - Bandopadhyay, Shreya
AU - Arthur, E. Madison
AU - Noarbe, Brenda
AU - Jullienne, Amandine
AU - Krkasharyan, Margret
AU - Tobin, Richard P.
AU - Pereverzev, Aleksandr
AU - Beevers, Samantha
AU - Venkatasamy, Lavanya
AU - Souza, Karienn A.
AU - Jupiter, Daniel C.
AU - Dabney, Alan
AU - Obenaus, Andre
AU - Newell-Rogers, M. Karen
AU - Shapiro, Lee A.
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/6/27
Y1 - 2024/6/27
N2 - Background: Traumatic brain injury (TBI) is a significant risk factor for Alzheimer’s disease (AD), and accumulating evidence supports a role for adaptive immune B and T cells in both TBI and AD pathogenesis. We previously identified B cell and major histocompatibility complex class II (MHCII)-associated invariant chain peptide (CLIP)-positive B cell expansion after TBI. We also showed that antagonizing CLIP binding to the antigen presenting groove of MHCII after TBI acutely reduced CLIP + splenic B cells and was neuroprotective. The current study investigated the chronic effects of antagonizing CLIP in the 5xFAD Alzheimer’s mouse model, with and without TBI. Methods: 12-week-old male wild type (WT) and 5xFAD mice were administered either CLIP antagonist peptide (CAP) or vehicle, once at 30 min after either sham or a lateral fluid percussion injury (FPI). Analyses included flow cytometric analysis of immune cells in dural meninges and spleen, histopathological analysis of the brain, magnetic resonance diffusion tensor imaging, cerebrovascular analysis, and assessment of motor and neurobehavioral function over the ensuing 6 months. Results: 9-month-old 5xFAD mice had significantly more CLIP + B cells in the meninges compared to age-matched WT mice. A one-time treatment with CAP significantly reduced this population in 5xFAD mice. Importantly, CAP also improved some of the immune, histopathological, and neurobehavioral impairments in 5xFAD mice over the ensuing six months. Although FPI did not further elevate meningeal CLIP + B cells, it did negate the ability of CAP to reduce meningeal CLIP + B cells in the 5xFAD mice. FPI at 3 months of age exacerbated some aspects of AD pathology in 5xFAD mice, including further reducing hippocampal neurogenesis, increasing plaque deposition in CA3, altering microgliosis, and disrupting the cerebrovascular structure. CAP treatment after injury ameliorated some but not all of these FPI effects.
AB - Background: Traumatic brain injury (TBI) is a significant risk factor for Alzheimer’s disease (AD), and accumulating evidence supports a role for adaptive immune B and T cells in both TBI and AD pathogenesis. We previously identified B cell and major histocompatibility complex class II (MHCII)-associated invariant chain peptide (CLIP)-positive B cell expansion after TBI. We also showed that antagonizing CLIP binding to the antigen presenting groove of MHCII after TBI acutely reduced CLIP + splenic B cells and was neuroprotective. The current study investigated the chronic effects of antagonizing CLIP in the 5xFAD Alzheimer’s mouse model, with and without TBI. Methods: 12-week-old male wild type (WT) and 5xFAD mice were administered either CLIP antagonist peptide (CAP) or vehicle, once at 30 min after either sham or a lateral fluid percussion injury (FPI). Analyses included flow cytometric analysis of immune cells in dural meninges and spleen, histopathological analysis of the brain, magnetic resonance diffusion tensor imaging, cerebrovascular analysis, and assessment of motor and neurobehavioral function over the ensuing 6 months. Results: 9-month-old 5xFAD mice had significantly more CLIP + B cells in the meninges compared to age-matched WT mice. A one-time treatment with CAP significantly reduced this population in 5xFAD mice. Importantly, CAP also improved some of the immune, histopathological, and neurobehavioral impairments in 5xFAD mice over the ensuing six months. Although FPI did not further elevate meningeal CLIP + B cells, it did negate the ability of CAP to reduce meningeal CLIP + B cells in the 5xFAD mice. FPI at 3 months of age exacerbated some aspects of AD pathology in 5xFAD mice, including further reducing hippocampal neurogenesis, increasing plaque deposition in CA3, altering microgliosis, and disrupting the cerebrovascular structure. CAP treatment after injury ameliorated some but not all of these FPI effects.
KW - Adaptive immune
KW - Alzheimer’s disease
KW - CD74
KW - Cerebrovascular
KW - Depression
KW - Fluid percussion injury
KW - Innate immune
KW - MHCII
KW - Neurobehavior
KW - Neuroinflammation
UR - http://www.scopus.com/inward/record.url?scp=85197105039&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85197105039&partnerID=8YFLogxK
U2 - 10.1186/s12974-024-03146-z
DO - 10.1186/s12974-024-03146-z
M3 - Article
C2 - 38937750
AN - SCOPUS:85197105039
SN - 1742-2094
VL - 21
SP - 165
JO - Journal of neuroinflammation
JF - Journal of neuroinflammation
IS - 1
M1 - 165
ER -