Journal Article

LOTUS overexpression accelerates neuronal plasticity after focal brain ischemia in mice

Takase, Hajime, Takei, Kohtaro, Kurihara, Yuji, Kawahara, Nobutaka, Yokoyama, Taka-akira

2017

Overview

Nogo receptor-1 (NgR1) and its ligands inhibit neuronal plasticity and limit functional recovery after brain damage such as ischemic stroke. We have previously shown that lateral olfactory tract usher substance (LOTUS) antagonizes NgR1-mediated signaling. Here, we investigated whether LOTUS enhances neuronal plasticity and functional recovery after brain focal ischemia in adult mice. Focal ischemic infarcts were induced in wild-type and LOTUS-overexpressing transgenic mice via middle cerebral artery occlusion. Endogenous LOTUS expression was increased in brain and cervical spinal cord of the contralateral side of ischemia in the chronic phase after brain ischemia. LOTUS overexpression accelerated midline-crossing axonal sprouting from the contralateral side to the ipsilateral side of ischemia in the medullar reticular formation and gray matter of denervated cervical spinal cord. Importantly, LOTUS overexpression improved neurological score highly correlated with laterality ratio of corticoreticular fibers of the medulla oblongata, indicating that LOTUS overexpression may overcome the inhibitory environment induced by NgR1 signaling for damaged motor pathway reconstruction after ischemic stroke. Thus, our data suggest that LOTUS overexpression accelerates neuronal plasticity in the brainstem and cervical spinal cord after stroke and LOTUS administration is useful for future therapeutic strategies.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animal cognition / Animals / Axon sprouting / Axonal plasticity / Biology and Life Sciences / Brain / Brain - metabolism / Brain - pathology / Brain damage / Brain Injuries - metabolism / Brain Injuries - pathology / Brain injury / Brain Ischemia - genetics / Brain Ischemia - metabolism / Brain stem / Calcium-Binding Proteins - genetics / Calcium-Binding Proteins - metabolism / Care and treatment / Cell receptors / Cellular signal transduction / Cerebral blood flow / Cerebral ischemia / Cervical Cord - metabolism / Correlation analysis / Development and progression / Disease Models, Animal / Functional plasticity / Genetic aspects / Health aspects / Immunoblotting / Infarction, Middle Cerebral Artery - genetics / Infarction, Middle Cerebral Artery - metabolism / Ischemia / Laboratory animals / Ligands / Male / Medicine and Health Sciences / Medulla oblongata / Mice / Mice, Inbred C57BL / Mice, Transgenic / Neuronal Plasticity - genetics / Neuronal Plasticity - physiology / Neurons / Neuroplasticity / Neurosciences / Neurosurgery / Nogo protein / Nogo Proteins - genetics / Nogo Proteins - metabolism / Nogo Receptor 1 - genetics / Nogo Receptor 1 - metabolism / Occlusion / Plasticity (neural) / Recovery / Recovery of function / Reticular formation / Spinal cord / Spinal plasticity / Stroke / Stroke - genetics / Stroke - metabolism / Substantia grisea / Transgenic animals / Transgenic mice / University graduates