Role of Neurotoxicity in Depression

  • Irena Smaga
  • Weronika Krzyżanowska
  • Bartosz Pomierny
  • Bogusława Budziszewska
  • Andrzej Pilc
  • Gabriel Nowak
Reference work entry
First Online:

Abstract

Despite years of research, the pathophysiology of depression and the mechanism of action in antidepressant drugs largely remain unknown. The subsequent hypotheses examining depression witnessed attention being paid to the decrease of the serotonin and noradrenaline synaptic concentrations, adaptive changes in the neurotransmitters receptor, activation of the immune system, hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, and enhanced glutamatergic activity. Current research suggests that disturbed neuronal plasticity and the degeneration of neurons and glia cells may be involved in the pathogenesis of depression. In fact, in depressed patients, structural changes are observed in several brain regions, mainly in the hippocampus. Also, in various animal models of depression, morphological alteration in neurons and glial cells is present besides depression-like behavioral changes. A lot of evidence indicates that an increased amount or activity of glucocorticoids, glutamate, and proinflammatory cytokines is the reason for these changes. In both animal models of depression and postmortem studies, a reduced neurogenesis in the dentate gyrus of the hippocampus; a decrease in the total number of neurons and astrocytes; a reduction of the dendritic length, branching density, or the number of synapses; and a decrease in the brain-derived neurotrophic factor were observed. Moreover, activation of microglia, a source of proinflammatory cytokines and reactive oxygen species, has a disadvantageous effect on neurons and astrocytes. However, it should be noted that not all of the studies demonstrate neurodegenerative changes in depression, or the glucocorticoids’ detrimental action, so further studies are needed in order to clearly determine the contribution of neurotoxic agents in the pathogenesis of depression and also the importance of the neuroprotective properties of some antidepressant drugs in their therapeutic effect.

Keywords

Animal models of depression Antidepressant Depression Neurotoxicity 

List of Abbreviations

5HT

Serotonin

ACTH

Adrenocorticotropic hormone

BDNF

Brain-derived neurotrophic factor

CMS

Chronic mild stress

CREB

Cyclic AMP response element-binding protein

CRF

Corticotropin-releasing factor

CRP

C-reactive protein

CUS

Chronic unpredictable stress

GFAP

Glial fibrillary acidic protein

HPA

Hypothalamic-pituitary-adrenal

LPS

Lipopolysaccharide

mPFC

Medial prefrontal cortex

NA

Noradrenaline

NMDA

n-methyl-d-aspartate

NOS

Nitric oxide synthase

PFC

Prefrontal cortex

ROS

Reactive oxygen species

SSRI

Selective serotonin reuptake inhibitors

TCA

Tricyclic antidepressant

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Irena Smaga
    • 1
  • Weronika Krzyżanowska
    • 1
  • Bartosz Pomierny
    • 1
  • Bogusława Budziszewska
    • 1
    • 3
  • Andrzej Pilc
    • 3
    • 4
  • Gabriel Nowak
    • 2
    • 3
  1. 1.Department of ToxicologyJagiellonian University Medical CollegeKrakówPoland
  2. 2.Department of PharmacobiologyJagiellonian University Medical CollegeKrakówPoland
  3. 3.Institute of PharmacologyPolish Academy of Sciences and Center of Excellence in NeuropsychopharmacologyKrakówPoland
  4. 4.Jagiellonian University Medical CollegeKrakówPoland

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