Revealing the cerebral regions and networks mediating vulnerability to depression: Oxidative metabolism mapping of rat brain

• Published in: Behavioural brain research Vol. 267; pp. 83 - 94
• Main Authors: Harro, Jaanus, Kanarik, Margus, Kaart, Tanel, Matrov, Denis, Kõiv, Kadri, Mällo, Tanel, Del Río, Joaquin, Tordera, Rosa M., Ramirez, Maria J.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 01.07.2014; Elsevier
• Subjects: Adult and adolescent clinical studies; Animal model; Animals; Behavior, Animal - physiology; Biological and medical sciences; Brain - physiopathology; Chronic Disease; Chronic stress; Depression; Depressive Disorder - etiology; Depressive Disorder - physiopathology; Disease Models, Animal; Dominance-Subordination; Electron Transport Complex IV - metabolism; Fundamental and applied biological sciences. Psychology; Male; Maternal Deprivation; Medical sciences; Mood disorders; Neural Pathways - physiopathology; Oxidative metabolism; Phenotype; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Rats; Resilience; Resilience, Psychological; Serotonin Agents; Stress, Psychological - complications; Stress, Psychological - physiopathology; Vertebrates: nervous system and sense organs; Vulnerability; Animal model; Depression; Chronic stress; Vulnerability; Oxidative metabolism; Resilience; Mood disorder; Rat; Rodentia; Central nervous system; Metabolism; Stress; Encephalon; Vertebrata; Chronic; Mammalia; Animal
• ISSN: 0166-4328; 1872-7549; 1872-7549
• DOI: 10.1016/j.bbr.2014.03.019

•Findings on neurobiology of depression in different animal models are hard to compare.•We analyzed data on brain oxidative metabolism across five rat models of depression.•Brain areas universally involved in stress response and vulnerability were revealed.•Diathesis-stress approach suggests brain regions mediating adaptation to stress.•Connectivity patterns in conditions of resilience and vulnerability are distinct. The large variety of available animal models has revealed much on the neurobiology of depression, but each model appears as specific to a significant extent, and distinction between stress response, pathogenesis of depression and underlying vulnerability is difficult to make. Evidence from epidemiological studies suggests that depression occurs in biologically predisposed subjects under impact of adverse life events. We applied the diathesis-stress concept to reveal brain regions and functional networks that mediate vulnerability to depression and response to chronic stress by collapsing data on cerebral long term neuronal activity as measured by cytochrome c oxidase histochemistry in distinct animal models. Rats were rendered vulnerable to depression either by partial serotonergic lesion or by maternal deprivation, or selected for a vulnerable phenotype (low positive affect, low novelty-related activity or high hedonic response). Environmental adversity was brought about by applying chronic variable stress or chronic social defeat. Several brain regions, most significantly median raphe, habenula, retrosplenial cortex and reticular thalamus, were universally implicated in long-term metabolic stress response, vulnerability to depression, or both. Vulnerability was associated with higher oxidative metabolism levels as compared to resilience to chronic stress. Chronic stress, in contrast, had three distinct patterns of effect on oxidative metabolism in vulnerable vs. resilient animals. In general, associations between regional activities in several brain circuits were strongest in vulnerable animals, and chronic stress disrupted this interrelatedness. These findings highlight networks that underlie resilience to stress, and the distinct response to stress that occurs in vulnerable subjects.