Long-Term Stress Degenerates, But Imipramine Regenerates, Noradrenergic Axons in the Rat Cerebral Cortex

Kitayama, Isao; Yaga, Takatoshi; Kayahara, Tetsuro; Nakano, Kenji; Murase, Sumio; Otani, Masato; Nomura, Junichi

doi:10.1016/s0006-3223(96)00502-1

Cited by 74 publications

(58 citation statements)

References 23 publications

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“…In animal models of neurodegenerative disorders, the shrinkage of TH-IR cells in the LC has often been described (German et al, 2005;Polak et al, 2011). Other microstructural changes in the LC and degeneration of noradrenergic axons have also been demonstrated in the frontal cortex in rats subjected to long-term stress (Kitayama et al, 1997;Kitayama et al, 2008). Together and waiting for additional morphological studies, these observations suggest that CCI exacerbates the neuronal damage induced by stress.…”

Section: Discussionmentioning

confidence: 99%

Pain exacerbates chronic mild stress-induced changes in noradrenergic transmission in rats

Bravo

Torres-Sánchez

Alba-Delgado

et al. 2014

European Neuropsychopharmacology

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Depression can influence pain and vice versa, yet the biological mechanisms underlying how one influences the pathophysiology of the other remains unclear. Dysregulation of locus coeruleusnoradrenergic transmission is implicated in both conditions, although it is not known whether this effect is exacerbated in cases of co-morbid depression and chronic pain. We studied locus coeruleus activity using immunofluorescence and electrophysiological approaches in rats subjected to unpredictable chronic mild stress (CMS, an experimental model of depression) and/or chronic constriction injury (CCI, a model of chronic neuropathic pain) for 2 weeks. CCI alone had no effect on any of the locus coeruleus parameters studied, while CMS led to a slight reduction in the electrophysiological activity of the locus coeruleus. Furthermore, CMS was associated with an increase in the number of tyrosine hydroxylase-positive cells in the locus coeruleus, although they were smaller in size. Interestingly, these effects of CMS were exacerbated when combined with CCI, even though no changes in the α2-adrenoreceptors or the noradrenaline transporter were observed in any group. Together, these findings suggest that CMS triggers several modifications in locus coeruleus-noradrenergic transmission that are exacerbated by co-morbid chronic pain. & 2014 Elsevier B.V. and ECNP. All rights reserved. E-mail address: esther.berrocoso@uca.es (E. Berrocoso). European Neuropsychopharmacology (]]]]) ], ]]]-]]]Please cite this article as: Bravo, L., et al., Pain exacerbates chronic mild stress-induced changes in noradrenergic transmission in rats. European Neuropsychopharmacology (2014), http://dx

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Section: Discussionmentioning

confidence: 99%

Pain exacerbates chronic mild stress-induced changes in noradrenergic transmission in rats

Bravo

Torres-Sánchez

Alba-Delgado

et al. 2014

European Neuropsychopharmacology

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“…In animal studies, changes in central serotonin levels influence axonal morphology, suggesting emotions, such as stress and depression, have a negative effect on the axonal morphology (29,30). Although few human experiments focus on the influence of emotions on axonal morphology, several studies have demonstrated that emotions and stress can change white matter integrity (31, 32).…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of white matter changes induced by meditation

Tang

Fan³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

301

233

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Using diffusion tensor imaging, several recent studies have shown that training results in changes in white matter efficiency as measured by fractional anisotropy (FA). In our work, we found that a form of mindfulness meditation, integrative body-mind training (IBMT), improved FA in areas surrounding the anterior cingulate cortex after 4-wk training more than controls given relaxation training. Reductions in radial diffusivity (RD) have been interpreted as improved myelin but reductions in axial diffusivity (AD) involve other mechanisms, such as axonal density. We now report that after 4-wk training with IBMT, both RD and AD decrease accompanied by increased FA, indicating improved efficiency of white matter involves increased myelin as well as other axonal changes. However, 2-wk IBMT reduced AD, but not RD or FA, and improved moods. Our results demonstrate the time-course of white matter neuroplasticity in short-term meditation. This dynamic pattern of white matter change involving the anterior cingulate cortex, a part of the brain network related to self-regulation, could provide a means for intervention to improve or prevent mental disorders.attention network test | anterior corona radiata | profile of mood states D iffusion tensor imaging (DTI) is a noninvasive MRI-based technique that can delineate white matter fibers in vivo. DTI is capable of measuring white matter's structural plasticity. Studies indicate that training or learning alters brain white matter (1-5). Fractional anisotropy (FA) is an important index for measuring the integrity of white matter fibers. In general, a higher FA value has been related to improved performance, and reduced FA has been found in normal aging and in neurological or psychiatric disorders (1,(6)(7)(8).FA alterations originate from several factors, such as changes in myelination, axon density, axonal membrane integrity, axon diameter, and intravoxel coherence of fiber orientation and others changes (1, 9). To understand the mechanisms of FA change, several DTI studies have examined axial diffusivity (AD) and radial diffusivity (RD), the most important indices associated with FA (6-8). Usually, alterations in AD are associated with axon morphological changes, such as changes in axonal density or caliber (10, 11). In contrast to AD, which signifies axonal morphology, RD implicates the character of the myelin. Decrease in RD implies increased myelination, and increase represents demyelination (2,3,8). This evidence in human neuroimaging studies is consistent with animal studies examining axons and myelination histologically and comparing them directly with DTI results (12, 13).To examine RD and AD it is best to have a significant change in FA (14). Thus, in our study we investigated AD and RD alteration patterns only where integrity of white matter fibers are enhanced (identified by FA increase). Numerous studies have used AD and RD changes in the location where FA changes are found to determine whether the FA changes are a result of axonic morphology or myelin (1-3, 6, 8, 1...

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“…Additionally, at the neuronal level, chronic stress has been associated with a retraction or atrophy of NE axonal projections, consistent with a reduced NE transmission. [39,40] Genetic vulnerabilities also play a role in response to chronic stress. [41] When subjected to chronic stress caused by intermittent cold exposure (7 days, 4 hr/day, 41C), inbred Wistar-Kyoto rats showed greater sensitization of both the brain NE system and the HPA axis, when compared with the outbred Sprague-Dawley rats.…”

Section: Chronic Stress and Ne Activitymentioning

confidence: 99%

Current perspectives of the roles of the central norepinephrine system in anxiety and depression

et al. 2010

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Norepinephrine (NE) is a major monoamine neurotransmitter that has widespread effects across multiple brain areas to regulate arousal and stress responses. The underlying function of the NE cortical system is to balance vigilance/scanning behavior with focused attention on novel environmental stimuli and the state of arousal. The central NE system is involved intrinsically with the stress response system, and dysregulation within the NE system has been implicated in the pathogenesis of anxiety and depressive disorders. Central NE activity paradoxically has either anxiogenic or anxiolytic effects, depending on whether the time course of the stress is acute or chronic, whether the stress is predictable or unpredictable, and which underlying brain regions are affected. Under conditions of chronic stress, NE system activity dysregulation of the hypothalamic-pituitary-adrenal system may turn a homeostatic stress response into a pathological stress response. Data suggest that the NE interplay with the serotonin system may exert neurobiological normalization of the pathophysiological state of anxious depression. Accordingly, pharmacological interventions targeting the NE system can result in anxiolytic, rather than anxiogenic, outcomes when used to treat patients with anxiety and depression. Depression and Anxiety 27:339-350, 2010. r r

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Long-Term Stress Degenerates, But Imipramine Regenerates, Noradrenergic Axons in the Rat Cerebral Cortex

Cited by 74 publications

References 23 publications

Pain exacerbates chronic mild stress-induced changes in noradrenergic transmission in rats

Pain exacerbates chronic mild stress-induced changes in noradrenergic transmission in rats

Mechanisms of white matter changes induced by meditation

Current perspectives of the roles of the central norepinephrine system in anxiety and depression

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