title: Functional connectivity in prenatally stressed rats with and without maternal treatment with ladostigil, a brain-selective monoamine oxidase inhibitor.
abstract: Stress during pregnancy in humans is known to be a risk factor for neuropsychiatric disorders in the offspring. Prenatal stress in rats caused depressive-like behavior that was restored to that of controls by maternal treatment with ladostigil (8.5 mg/kg per day), a brain-selective monoamine oxidase (MAO) inhibitor that prevented increased anxiety-like behavior in stressed mothers. Ladostigil inhibited maternal striatal MAO-A and -B by 45-50% at the time the pups were weaned. Using resting state-functional connectivity magnetic resonance imaging on rat male offspring of control mothers, and mothers stressed during gestation with and without ladostigil treatment, we identified neuronal connections that differed between these groups. The percentage of significant connections within a predefined predominantly limbic network in control rats was 23.3 within the right and 22.0 within the left hemisphere. Prenatal stress disturbed hemispheric symmetry, resulting in 30.2 and 21.6%, significant connections in the right and left hemispheres, respectively, but this was fully restored in the maternal ladostigil group to 24.6% in both hemispheres. All connections that were modified in prenatally stressed rats and restored by maternal drug treatment were associated with the dopaminergic system. Specifically, we observed that restoration of the connections of the right nucleus accumbens shell with frontal areas, the cingulate, septum and motor and sensory cortices, and those of the right globus pallidus with the infra-limbic and the dentate gyrus, were most important for prevention of depressive-like behavior.
authors.affiliation: MRI Lab, The Human Biology Research Center, Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University Medical Center, Ein Karem, PO Box 12000, Jerusalem 91120, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Goelman
authors.forename: R
authors.initials: R
authors.lastname: Ilinca
authors.forename: I
authors.initials: I
authors.lastname: Zohar
authors.forename: M
authors.initials: M
authors.lastname: Weinstock
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000503:physiopathology; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000254:growth & development / Q000503:physiopathology*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D007189:Indans / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008425:Maternal Behavior / Q000187:drug effects / Q000502:physiology; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000627:therapeutic use*; D009434:Neural Pathways / Q000254:growth & development / Q000503:physiopathology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy* / Q000503:physiopathology; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D017208:Rats, Wistar; D012146:Rest; D013315:Stress, Psychological / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: C423264:(N-propargyl-(3R) aminoindan-5-yl)-ethyl methyl carbamate; D007189:Indans; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase
keywords: dopaminergic transmission; forced swim test; hemispheric symmetry; nucleus accumbens; resting state-functional connectivity