Peripheral inflammation preceeding ischemia impairs neuronal survival through mechanisms involving miR-127 in aged animals

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Loppi , S , Korhonen , P , Bouvy-Liivrand , M , Caligola , S , Turunen , T A , Turunen , M P , de Sande , A H , Kolosowska , N , Scoyni , F , Rosell , A , Garcia-Berrocoso , T , Lemarchant , S , Dhungana , H , Montaner , J , Koistinaho , J , Kanninen , K M , Kaikkonen , M U , Giugno , R , Heinäniemi , M & Malm , T 2021 , ' Peripheral inflammation preceeding ischemia impairs neuronal survival through mechanisms involving miR-127 in aged animals ' , Aging Cell , vol. 20 , no. 1 , 13287 . https://doi.org/10.1111/acel.13287

Title: Peripheral inflammation preceeding ischemia impairs neuronal survival through mechanisms involving miR-127 in aged animals
Author: Loppi, Sanna; Korhonen, Paula; Bouvy-Liivrand, Maria; Caligola, Simone; Turunen, Tiia A.; Turunen, Mikko P.; de Sande, Ana Hernandez; Kolosowska, Natalia; Scoyni, Flavia; Rosell, Anna; Garcia-Berrocoso, Teresa; Lemarchant, Sighild; Dhungana, Hiramani; Montaner, Joan; Koistinaho, Jari; Kanninen, Katja M.; Kaikkonen, Minna U.; Giugno, Rosalba; Heinäniemi, Merja; Malm, Tarja
Other contributor: University of Helsinki, Neuroscience Center
University of Helsinki, Neuroscience Center
Date: 2021-01
Language: eng
Number of pages: 13
Belongs to series: Aging Cell
ISSN: 1474-9718
DOI: https://doi.org/10.1111/acel.13287
URI: http://hdl.handle.net/10138/332998
Abstract: Ischemic stroke, the third leading cause of death in the Western world, affects mainly the elderly and is strongly associated with comorbid conditions such as atherosclerosis or diabetes, which are pathologically characterized by increased inflammation and are known to influence the outcome of stroke. Stroke incidence peaks during influenza seasons, and patients suffering from infections such as pneumonia prior to stroke exhibit a worse stroke outcome. Earlier studies have shown that comorbidities aggravate the outcome of stroke, yet the mediators of this phenomenon remain obscure. Here, we show that acute peripheral inflammation aggravates stroke-induced neuronal damage and motor deficits specifically in aged mice. This is associated with increased levels of plasma proinflammatory cytokines, rather than with an increase of inflammatory mediators in the affected brain parenchyma. Nascent transcriptomics data with mature microRNA sequencing were used to identify the neuron-specific miRNome, in order to decipher dysregulated miRNAs in the brains of aged animals with stroke and co-existing inflammation. We pinpoint a previously uninvestigated miRNA in the brain, miR-127, that is highly neuronal, to be associated with increased cell death in the aged, LPS-injected ischemic mice. Target prediction tools indicate that miR-127 interacts with several basally expressed neuronal genes, and of these we verify miR-127 binding to Psmd3. Finally, we report reduced expression of miR-127 in human stroke brains. Our results underline the impact of peripheral inflammation on the outcome of stroke in aged subjects and pinpoint molecular targets for restoring endogenous neuronal capacity to combat ischemic stroke.
Subject: aging
inflammation
microRNA
proteasome
sequencing
stroke
FACTOR-KAPPA-B
BRAIN-DAMAGE
26S PROTEASOME
EXPRESSION
ASTROCYTES
REDUCTION
DISEASE
STROKE
INJURY
MICE
3112 Neurosciences
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