Highlights d Central amygdala NPY neurons control feeding d Stress combined with a high-caloric diet increases NPY expression in the central amygdala d Insulin controls NPY expression in central amygdala neurons d Stress combined with a high-caloric diet causes insulin resistance in central amygdala
layer of the superior colliculus; uCT, micro-computed tomography; VCO 2 , carbon dioxide production; VDB, nucleus of the vertical limb of the diagonal band; VO 2 , oxygen consumption; WT, wildtype.
Multiple sclerosis (MS) is a neurodegenerative autoimmune disease, where chronic inflammation plays an essential role in its pathology. A feature of MS is the production of autoantibodies stimulated by an altered-peptide-ligand response and epitope spreading, resulting in loss of tolerance for self-proteins. The involvement of autoantibodies in MS pathogenesis has been suggested to initiate and drive progression of inflammation; however, the etiology of MS remains unknown. The effect of etomoxir and interferon-β (IFN-β) was examined in an experimental-autoimmune-encephalomyelitis (EAE) model of MS. Moreover, the impact of etomoxir and IFN-β on recognition of brain proteins in serum from EAE rats was examined with the purpose of identifying the autoantibody reactivities involved in MS. Animals treated with etomoxir on day 1 exhibited a statistically significantly lower disease score than animals treated with IFN-β (on day 1 or 5) or placebo. Etomoxir treatment on day 5 resulted in a significantly lower disease score than IFN-β treatment on day 1. After disease induction antibodies was induced to a broad pallet of antigens in the brain. Surprisingly, by blocking CPT1 and therewith lipid metabolism several alterations in the antibody response was observed suggesting that autoantibodies play a role in the EAE animal model.
21 22 23 Following neurotrauma, secondary degeneration of neurons and glia adjacent to the injury 24 leads to further functional loss. A combination of ion channel inhibitors (lomerizine + oxATP 25 + YM872) has been shown to be effective at limiting structural and functional loss due to 26 secondary degeneration. Here we assess efficacy of the combination where oxATP is 27 replaced with Brilliant Blue G (BBG), a more clinically applicable P2X7 receptor inhibitor.
28Partial optic nerve transection was used to model secondary degeneration in adult female rats. 29 Animals were treated with combinations of lomerizine + YM872 + oxATP or lomerizine + 30 YM872 + BBG, delivered via osmotic mini pump directly to the injury site. Outcomes 31 assessed were Iba1+ and ED1+ microglia and macrophages, oligodendroglial cell numbers, 32 node/paranode structure and visual function using the optokinetic nystagmus test. The 33 lomerizine + BBG + YM872 combination was at least as effective at the tested 34 concentrations as the lomerizine + oxATP + YM872 combination at preserving 35 node/paranode structure and visual function when delivered locally. However, neither ion 36 channel inhibitor combination significantly improved microglial/macrophage nor 37 oligodendroglial numbers compared to vehicle treated controls. In conclusion, a locally 38 delivered combination of ion channel inhibitors incorporating lomerizine + BBG + YM872 is 39 at least as effective at limiting secondary degeneration following partial injury to the optic 40 nerve as the combination incorporating oxATP. 41 42 43 Keywords: secondary degeneration; neurotrauma; ion channel inhibitor; myelin; visual 44 function 45 46 47 Following neurotrauma, a series of metabolic and structural changes are propagated in 48 initially undamaged tissue, associated with increased intracellular Ca 2+ , oxidative stress and 49 apoptotic cell death of neurons and glia (Dong et al. 2009). Since the initial insult is often 50 unavoidable, treatments for functional recovery after neurotrauma focus heavily on limiting 51 this secondary damage (Doan et al. 2016). However, despite extensive research, effective 52 pharmacotherapeutic treatments for secondary degeneration following neurotrauma are 53 limited (Kwon et al. 2011). In order to successfully limit secondary degeneration following 54 neurotrauma, it is important to test efficacy of treatments in appropriate animal models of 55 injury. Partial optic nerve transection is an established and useful model for investigating 56 secondary degeneration, where the dorsal optic nerve of adult rats is partially transected, 57 allowing for spatial separation between the primary and subsequent secondary degeneration 58 (Levkovitch-Verbin et al. 2003; Blair et al. 2005). The model has been further characterised 59 and employed to assess efficacy of pharmacotherapeutics for secondary degeneration, 60 delivered directly to the injury site using osmotic mini-pumps (Fitzgerald et al. 2009a; 61 Fitzgerald et al. 2009b; Savigni et al. 2013; O'Hare Doig ...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.