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Volume 9
Journal of Neurology and Neuroscience
ISSN: 2171-6625
Page 49
JOINT EVENT
July 23-24, 2018 Birmingham, UK
&
24
th
International Conference on
Neuroscience and Neurochemistry
26
th
Edition of International Conference on
Clinical Psychology and Neuroscience
A quest to model
in vivo
mild mitochondrial dysfunction in mice
Serena Asslih
1
, O Damri
1
, A Daraushe
1
, H Einat
2
, N Kara
1, 2
and
G Agam
1
1
Ben-Gurion University of the Negev, Israel
2
Tel Aviv-Yaffo Academic College, Israel
D
espite the high prevalence (~1% of the adult population) of bipolar-disorder its pathophysiology or the mechanism
by which effective medications exert their therapeutic effect has not yet been unraveled but data from other groups
and ours indicate brain mitochondrial dysfunction in the patients and beneficial effects of mood stabilizers (anti-bipolar
drugs) on mitochondrial function. We therefore aim to model mild mitochondrial dysfunction in mice using the oxidative
phosphorylation (OxPhos) complex I inhibitor, rotenone, to induce affective-like behavior. Adult ICR mice were treated daily
with 0.25, 0.5, 0.75, 1.2 and1.5 mg/kg/day rotenone for four, six and eight weeks following which the mice were subjected to a
battery of behavioral tests [open field, elevated plus maze (EPM), sweet-solution (saccharin) preference (SSP), rotarod, forced-
swim test (FST) and amphetamine-induced hyperactivity] and neurochemical assays. Chronic administration of all rotenone
doses for four weeks did not affect spontaneous activity or time spent in the center of the open field, SSP or behavior in the
EPM. 0.5 mg/kg/day for four weeks induced a trend for attenuation of amphetamine-induced hyperactivity. 0.75 mg/kg/day
for four or six weeks reduced the immobility time in the FST and protein levels of all mitochondrial respiration complexes
except for complex IV in the hippocampus with an inverse effect in the frontal-cortex. As for mitochondrial-respiration –
there was a trend for upregulation in the hippocampus and down regulation in the frontal-cortex. Eight weeks of treatment
significantly increased the immobility-time and reduced mitochondrial -respiration without affecting protein levels of LC-3II
and mitochondrial-respiration complexes. In conclusion, 0.75 mg/kg/day rotenone exhibited dichotomial effect on depressive-
like behavior reminiscent of bipolarity. We are currently investigating whether Reactive Oxygen-Species (ROS)-scavengers
and/or autophagy enhancers rescue the bipolar-like behavior and neurochemical markers.
Recent Publications
1. Cataldo A M, et al. (2010) Abnormalities in mitochondrial structure in cells from patients with bipolar disorder. Am
JPathol 177:575-585.
2. Betarbet R, et al. (2000) Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nature
Neuroscience 3:1301-1306.
3. Fattal O, et al. (2006) Review of the literature on major mental disorders in adult patients with mitochondrial diseases.
Psychosomatics 47:1-7.
4. Grover S, et al. (2006) Mania as a first presentation in mitochondrial myopathy. Psych Clin Neurosci 60:774-775.
5. Kato T, et al. (1997) Increased levels of a mitochondrial DNA deletion in the brain of patients with bipolar disorder.
Biol Psych 42:871-875.
Biography
Serena Asslih is an MSc student at Ben-Gurion University, Israel. She carries out a behavioral and molecular research project aiming at mimicking mitochondrial
dysfunction robustly reported in bipolar disorder under Prof Galila Agam's mentorship. In parallel, to achieve knowledge and practice in the preclinical world, which
is her central interest, she took upon herself shift duties in hospital laboratories.
Serenaa@post.bgu.ac.ilSerena Asslih et al., J Neurol Neurosci 2018, Volume 9
DOI: 10.21767/2171-6625-C2-012