Platelet Depletion is Effective in Ameliorating Anxiety-Like Behavior and Reducing the Pro-Inflammatory Environment in the Hippocampus in Murine Experimental Autoimmune Encephalomyelitis

Abstract

The neuropsychiatric symptoms of multiple sclerosis (MS), such as anxiety and depression, can result from disease activity itself as well as psychological reaction to an unfavorable diagnosis. Accordingly, the literature reports evidence of increased anxiety-like behavior in experimental autoimmune encephalomyelitis (EAE), an accepted MS model. Due to the recently described critical role of platelets in inflammation and autoimmune disease, we examined the relationship between platelets, inflammation, and anxiety-like behavior in EAE. In the elevated plus maze, EAE-induced C57BL/6J mice showed decreased time spent in the open arms relative to vehicle-only controls, demonstrating an increase in anxiety-like behavior. This effect occurred in the presence of platelet–neuron association, but absence of lymphocytic infiltration, in the hippocampal parenchyma. Platelet depletion at the pre-clinical disease stage, using antibody-mediated lysis prevented the EAE-induced increase in anxiety-like behavior, while no significant difference in distance moved was recorded. Furthermore, platelet depletion was also associated with reduction of the pro-inflammatory environment to control levels in the hippocampus and prevention of EAE disease symptomology. These studies demonstrate the high efficacy of a platelet-targeting approach in preventing anxiety-like symptoms and clinical manifestations of EAE and have implications for the treatment of neuropsychiatric symptoms in MS.

Caffeine Modulates Cadmium-Induced Oxidative Stress, Neuroinflammation, and Cognitive Impairments by Regulating Nrf-2/HO-1 In Vivo and In Vitro

“…Immunofluorescence was performed as described previously with some modification [32,33]. Slides with brain sections were washed twice with 1% PBS for 10 min, then proteinase-k was added, followed by incubation for 5 min at room temperature.…”

Platelets as Mediators of Neuroinflammation and Thrombosis

“…Addressing neuropsychiatric symptoms of MS, such as anxiety and depression, it has recently been shown that GPIb antibody-mediated platelet depletion prevented the EAE-induced increase in anxiety-like behavior which was associated with reduction of the pro-inflammatory environment to control levels in the hippocampus of mice ( 166 ).…”

Platelets in Neurodegenerative Conditions—Friend or Foe?

“…Recent work investigating the brains of EAE-induced mice demonstrated that platelets were also present in the parenchyma of the hippocampus, including in the fimbria and in close proximity to neuronal cell bodies in the dentate gyrus and CA1 region (14). This phenotype was associated with the formation of a neuroinflammatory environment, supposedly due to plateletneuron associations (14).…”

“…This phenotype was associated with the formation of a neuroinflammatory environment, supposedly due to plateletneuron associations (14). However, this occurred in the absence of inflammatory cell infiltration, further highlighting the role of platelets in the initiation of EAE (14). In the same study, the pro-inflammatory environment in the hippocampus of EAEinduced mice, as well as their increased anxiety-like behavior, were improved following platelet depletion with polyclonal antiplatelet glycoprotein Ib α chain antibodies, suggesting that platelets could serve as a potential target for the amelioration of the symptoms of MS (14).…”

“…In conditions where the vascular integrity is altered or disturbed direct interactions with neural cells are possible. Platelet activity has been observed within the brain parenchyma following lesion (12) and stroke (13), as well as in the brain of experimental autoimmune encephalomyelitis (EAE)-induced mice (14). Furthermore, a direct interaction between platelets and neuronal cells has been reported, as they can bind central nervous system-specific glycolipid structures that are present in the lipid rafts of neuronal processes (15).…”