Degeneration of locus coeruleus axons in stress-induced depression model.
Antidepressants such as desipramine induce axonal regeneration of brain noradrenergic neurons. This novel action of antidepressants suggests the involvement of degeneration or retraction of brain noradrenergic axons in the pathophysiology of clinical depression. The present study was designed to further confirm this view in an animal model of stress-induced depression. The depression model was produced by exposing rats to prolonged forced walking stress. To see if axonal degeneration of noradrenergic neurons occurred in the depression model, the density of noradrenergic axons in the cerebral cortex was assessed by three different methods, antidromic stimulation technique, retrograde tracing with horseradish peroxidase and immunohistochemical staining with dopamine-beta-hydroxylase antiserum. These methods all assured of degenerative changes of noradrenergic axon terminals in the depression model. Furthermore, it was found that repeated treatments of the depression-model rats with imipramine could cause regeneration of cortical noradrenergic axons. These findings support the view that degeneration or retraction of noradrenergic axons is involved in the pathophysiology of depression.
Kitayama
I
I
Department of Psychiatry, Mie University School of Medicine, Tsu, Japan.
Nakamura
S
S
Yaga
T
T
Murase
S
S
Nomura
J
J
Kayahara
T
T
Nakano
K
K
D000818:Animals; D001369:Axons / Q000502:physiology*; D003866:Depressive Disorder / Q000209:etiology / Q000473:pathology*; D004594:Electrophysiology; D005260:Female; D006735:Horseradish Peroxidase; D007099:Imipramine / Q000494:pharmacology; D007150:Immunohistochemistry; D008125:Locus Coeruleus / Q000473:pathology*; D008297:Male; D009410:Nerve Degeneration / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000150:complications / Q000473:pathology*; D018998:Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate; D014909:Wheat Germ Agglutinins
D018998:Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate; D014909:Wheat Germ Agglutinins; D006735:Horseradish Peroxidase; D007099:Imipramine; D009638:Norepinephrine