ABSTRACTS – ORAL PRESENTATIONS - AMCA, spol. s r.o.

P38. EVIDENCE OF ABNORMAL PERIPHERAL CYTOKINE PROFILE IN PORCINE MODEL
OF HUNTINGTON’S DISEASE
Ivona Valekova 1,3 , Jiri Klima 1 , Helena Kupcova Skalnikova 2 , Karla Jarkovska 2 ,
Stefan Juhas 1 , Jan Motlik 1
1
Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and
Genetics, v.v.i., AS CR, Libechov, Czech Republic;
2
Laboratory of Biochemistry and Molecular Biology of Germ Cells, Institute of Animal
Physiology and Genetics, v.v.i., AS CR, Libechov, Czech Republic;
3
Department of Cell Biology, Faculty of Science, Charles University in Prague, Prague,
Czech Republic
valekova@iag.cas.cz
Huntington´s disease (HD) is a devastating monogenic neurodegenerative disorder with
detrimental effects of abnormal expansion of the CAG trinucleotide repeat within the
coding region of the huntingtin gene. HD is characterized by brain neurodegeneration
with a loss of brain neurons located predominantly in the striatum. The disease onset
is in the middle age and is generally marked by progressive cognitive, psychiatric and
motor impairment. Currently, there is no HD treatment available.
Although HD causes widespread changes in CNS, there is a parallel immune activation in
the periphery. The pro-inflammatory cytokine levels are increased earliest in the disease
course, long before the onset of motor dysfunction. This phenomenon can be observed
many years before the predicted onset of neurological symptoms (Björkvist et al., 2008),
which designates immune activation as a potential biomarker of HD progression.
The early disease progression is monitored on unique minipig model. In our lab we have
recently generated a biomedical model of HD - a miniature pig transgenic for N-terminal
part of the mutated human huntingtin (mt HTT, 548aa, 124Q) (Baxa et al., 2013). Agematched
control and HD transgenic minipigs with the same genetic background were
included in this study.
The principal aims of this study are (i) to characterize the activation of innate immune
system in control and HD transgenic animals, (ii) to monitor the levels of cytokines
during ageing and disease course, (iii) to detect monocyte activation as a possible source
of peripheral cytokines.
The expression of selected thirteen cytokines, chemokines and growth factors were
examined by targeted proteomic profiling using cytometric approaches. Isolated
non-mature CD14+ monocytes were activated and analyzed using porcine Luminex
immunoassay.
Our data indicate significant changes between control and HD transgenic miniature
pigs mainly in the level of IL-8, both in blood serum and monocytes in the age of 13-
15 months. The cytokine profiling together with monitoring of monocyte activation is
regularly continuing in three month intervals.
Early changes identified in HD transgenic pigs may help to clarify the pathological
mechanisms underlying the disease development, and thus could offer an obtainment
of accessible non-invasive bioindicators of disease progress.
132 Analytical Cytometry VII