Inflammation modulates anxiety in an animal model of multiple sclerosis.
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by inflammation, but also degenerative changes. Besides neurological deficits, the rate of affective disorders such as depression and anxiety is at least six fold increased. Many aspects of MS can be mimicked in the animal model of myelin oligodendrocyte glycoprotein experimental autoimmune encephalomyelitis (MOG-EAE). Here we investigate behavioral changes in C57BL/6 mice suffering from mild MOG-EAE. In the later phase of the disease, mice were subjected to behavioral tests including the light-dark-box (LD Box), the acoustic startle response (SR) with a pre-pulse inhibition protocol as well as the learned helplessness (LH) paradigm. Behavioral data were correlated with the motor performance in an open field and rotarod test (RR). In the RR and open field, there was no significant difference in the motor performance between controls and mice suffering from mild MOG-EAE. Yet EAE mice displayed an increased anxiety-like behavior with a 23% reduction of the time spent in the bright compartment of the LD Box as well as an increased SR. In the LH paradigm, mice suffering from MOG-EAE were twice as much prone to depressive-like behavior. These changes correlate with an increase of hippocampal tissue tumor necrosis factor alpha levels and neuronal loss in the hippocampus. Modulation of monoaminergic transmission by chronic application of the antidepressant amitriptyline resulted in a decreased startle reaction and increased hippocampal norepinephrine levels. These data imply that chronic inflammation in the CNS may impact on emotional responses in rodent models of anxiety.
Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, 44791 Bochum, Germany.
Isabella
I
Peruga
Silvia
S
Hartwig
Jan
J
Thöne
Bernhard
B
Hovemann
Ralf
R
Gold
Georg
G
Juckel
Ralf A
RA
Linker
D000161:Acoustic Stimulation / Q000009:adverse effects; D000639:Amitriptyline / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D002490:Central Nervous System / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D016207:Cytokines / Q000378:metabolism; D003623:Dark Adaptation / Q000187:drug effects / Q000502:physiology; D003711:Demyelinating Diseases / Q000209:etiology; D003863:Depression / Q000209:etiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000009:adverse effects; D006380:Helplessness, Learned; D007249:Inflammation / Q000150:complications* / Q000209:etiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009103:Multiple Sclerosis / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000009:adverse effects; D037342:Pertussis Toxin / Q000009:adverse effects; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011571:Psychoacoustics; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D045442:Rotarod Performance Test / Q000379:methods; D013238:Stereotaxic Techniques; D013997:Time Factors
D000929:Antidepressive Agents, Tricyclic; D016207:Cytokines; D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D000639:Amitriptyline; D037342:Pertussis Toxin; D010751:Phosphopyruvate Hydratase