RT Journal Article
SR Electronic
T1 L7 Laquinimod in the R6/2 mouse model of huntington’s disease
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP A92
OP A92
DO 10.1136/jnnp-2016-314597.262
VO 87
IS Suppl 1
A1 Gisa Ellrichmann
A1 Alina Blusch
A1 Oluwaseun Fatoba
A1 Janine Brunner
A1 Kalliopi Pitarokoili
A1 Liat Hayardeny
A1 Carsten Saft
A1 Ralf Gold
YR 2016
UL http://jnnp.bmj.com/content/87/Suppl_1/A92.2.abstract
AB Introduction The transgenic mouse model R6/2 (141–157 CAG repeats) of Huntington’s disease (HD) recapitulates basic pathophysiological similarities of HD and some of its clinical symptoms.Laquinimod as an immunomodulatory orally substance has shown to downregulate astrocytic and microglial activation which are common pathways in neurodegenerative diseases. Methods We investigated the therapeutic efficacy of laquinimod in the R6/2 mouse model treating the animals with different concentrations of laquinimod (0.5/1.5/5/25 mg/kg body weight (bw)) by oral gavage. We explore the neuroprotective potential of laquinimod analysing behaviour (rotarod), weight, survival and histopathological changes after treatment. Results Oral treatment with laquinimod (especially 0.5 mg/kg bw) not only improved motor impairment but also weight course and extended survival in R6/2 mice. R6/2 mice that were treated with 0.5 mg laquinimod showed longer life spans, as determined by Kaplan Meier analysis (p-value = 0.1). Upon analysis of motor performance, latency-to-fall values during rotarod testing in R6/2 mice were significantly different at the age of 12 weeks in the 0.5 and 25 mg/kg bw treated group (p*<0.05).In the histological analysis, laquinimod treatment resulted in preservation of morphologically intact neurons in the motor cortex and striatum as revealed by neuronal marker NeuN and medium spiny neuron’s (MSN’s) marker DARPP-32. Biochemical analysis also showed significant increase in brain derived neurotrophic factor (BDNF) level in the cortical (*p < 0.05) but not in striatal neurons. These effects seem to be mainly based on BDNF-pathways, influence on oxidative stress, and possibly reduction of neuroinflammatory influences. Conclusion Together, these findings suggest that treatment with laquinimod could provide a potential therapy for the up-regulation or modulation of neuroprotective pathways in HD.