Depression and antidepressants: molecular and cellular aspects

Abstract

Clinical depression is viewed as a physical and psychic disease process having a neuropathological basis, although a clear understanding of its ethiopathology is still missing. The observation that depressive symptoms are influenced by pharmacological manipulation of monoamines led to the hypothesis that depression results from reduced availability or functional deficiency of monoaminergic transmitters in some cerebral regions. However, there are limitations to current monoamine theories related to mood disorders. Recently, a growing body of experimental data has showed that other classes of endogenous compounds, such as neuropeptides and amino acids, may play a significant role in the pathophysiology of affective disorders. With the development of neuroscience, neuronal networks and intracellular pathways have been identified and characterized, describing the existence of the interaction between monoamines and receptors in turn able to modulate the expression of intracellular proteins and neurotrophic factors, suggesting that depression/antidepressants may be intermingled with neurogenesis/neurodegenerative processes.

Insulin resistance in brain alters dopamine turnover and causes behavioral disorders

“…The monoamine hypothesis of depression postulates that the deficiency of neurotransmitters, such as dopamine, serotonin, and catecholamines, in the brain is responsible for the manifestations of depression (42). Assessment of the levels of serotonin and catecholamines, as well as their degradation products, in the brains of 17-mo-old NIRKO mice revealed no differences from control ( Fig.…”

CRTH2, a prostaglandin D2 receptor, mediates depression-related behavior in mice

“…Previous studies found that depression primarily results from impaired monoaminergic neurotransmission systems [1,2]. The glutamatergic and GABAergic systems as well as several neuropeptide systems have also been the focus of pathophysiological studies on depression [1,2].…”

“…The glutamatergic and GABAergic systems as well as several neuropeptide systems have also been the focus of pathophysiological studies on depression [1,2]. Inflammatory cytokines and molecular intermediates are also suggested to be involved in depression, presumably by regulating neurotransmitter metabolism, neuroendocrine function, and synaptic function [4].…”

“…Approximately, 15% of the population will experience depression at some point during their lifetime, and depression is associated with high morbidity and mortality [2]. Despite its high prevalence and socioeconomic burden, little is known about the etiology of depression.…”

Compensatory Neurogenesis in the Injured Adult Brain

“…Performing physical exercise and environmental enrichment have also been shown to enhance hippocampal neurogenesis, potentially through increased expression of a range of mitogenic factors such as BDNF, FGF2, NGF, IGF-1 and VEGF as well as phosphorylation of cAMP-response binding protein (CREB) (Nithianantharajah, et al, 2006, Van Praag, 2008, Llorens-Martín, et al, 2009, Lafenetre, et al, 2011 and may provide an appealing noninvasive therapeutic approach for the treatment of chronic TLE (Dhanushkodi, et al, 2008, Arida, et al, 2009. Antidepressant therapy in chronic TLE is another interesting approach for increasing neurogenesis and reducing cognitive impairments, as antidepressant therapy enhances hippocampal neurogenesis probably via increases in levels of serotonin, noradrenaline, BDNF, CREB and a range of other mitogenic factors (Sahay, et al, 2007, Thomas, et al, 2008, Lanni, et al, 2009. In particular, a recent study demonstrated that repeated administration of the antidepressant agent citalopram counteracted kainic acidinduced neuronal loss and dispersion of PSA-NCAM-positive cells within the granule cell layer of the hippocampus (Jaako, et al, 2011).…”