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The anti-asthmatic drug, montelukast, modifies the neurogenic potential in the young healthy and irradiated brain

Journal article
Authors Yohanna Eriksson
Martina Boström
Åsa P Sandelius
Kaj Blennow
Henrik Zetterberg
Hans-Georg Kuhn
Marie Kalm
Published in Cell Death & Disease
Volume 9
Issue 7
ISSN 2041-4889
Publication year 2018
Published at Institute of Neuroscience and Physiology
Institute of Clinical Sciences, Department of Oncology
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
Institute of Neuroscience and Physiology, Department of Pharmacology
Language en
Links dx.doi.org/10.1038/s41419-018-0783-...
Keywords hippocampal neurogenesis, cognitive impairment, cns, sensitivity, dysfunction, inhibition, activation, disorders, microglia, ischemia, Cell Biology
Subject categories Cancer and Oncology, Neurology

Abstract

Brain tumors are the most common form of solid tumors in children. Due to the increasing number of survivors, it is of importance to prevent long-term treatment-induced side effects. Montelukast, a leukotriene receptor antagonist, may have the desired neuroprotective properties. The aim of the study was to determine whether montelukast could reduce adverse effects of cranial irradiation (CIR) to the young brain. Daily injections of montelukast or vehicle was given to young mice for 4 or 14 days in combination with CIR or under normal conditions. Montelukast treatment for 4 days protected against cell death with 90% more cell death in the vehicle group compared to the montelukast group 24 h after CIR. It also resulted in less microglia activation 6 h after CIR, where montelukast lowered the levels of CD68 compared to the vehicle groups. Interestingly, the animals that received montelukast for 14 days had 50% less proliferating cells in the hippocampus irrespective of receiving CIR or not. Further, the total number of neurons in the granule cell layer was altered during the sub-acute phase. The number of neurons was decreased by montelukast treatment in control animals (15%), but the opposite was seen after CIR, where montelukast treatment increased the number of neurons (15%). The results show beneficial effects by montelukast treatment after CIR in some investigated parameters during both the acute phase and with longer drug treatment. However, it also resulted in lower proliferation in the hippocampus under normal conditions, indicating that the effects of montelukast can be either beneficial or unfavorable, depending on the circumstances.

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