Dendritic Spines in Depression: What We Learned from Animal Models

Abstract

Depression, a severe psychiatric disorder, has been studied for decades, but the underlying mechanisms still remain largely unknown. Depression is closely associated with alterations in dendritic spine morphology and spine density. Therefore, understanding dendritic spines is vital for uncovering the mechanisms underlying depression. Several chronic stress models, including chronic restraint stress (CRS), chronic unpredictable mild stress (CUMS), and chronic social defeat stress (CSDS), have been used to recapitulate depression-like behaviors in rodents and study the underlying mechanisms. In comparison with CRS, CUMS overcomes the stress habituation and has been widely used to model depression-like behaviors. CSDS is one of the most frequently used models for depression, but it is limited to the study of male mice. Generally, chronic stress causes dendritic atrophy and spine loss in the neurons of the hippocampus and prefrontal cortex. Meanwhile, neurons of the amygdala and nucleus accumbens exhibit an increase in spine density. These alterations induced by chronic stress are often accompanied by depression-like behaviors. However, the underlying mechanisms are poorly understood. This review summarizes our current understanding of the chronic stress-induced remodeling of dendritic spines in the hippocampus, prefrontal cortex, orbitofrontal cortex, amygdala, and nucleus accumbens and also discusses the putative underlying mechanisms.

Electroacupuncture Regulates Hippocampal Synaptic Plasticity via miR-134-Mediated LIMK1 Function in Rats with Ischemic Stroke

“…Moreover, EA promoted synaptic-dendritic spine regeneration. Dendritic spine is the tiny protrusions with multi-dense body and ion channels on the surface of various types of neurons, which serve as cellular substrates of brain connectivity and the major sites of information processing in the brain [38, 39]. Evidence is increasing that synaptic-dendritic plasticity enables the encoding of memory [40].…”

Orbitofrontal cortex 5-HT2A receptor mediates chronic stress-induced depressive-like behaviors and alterations of spine density and Kalirin7

“…Many studies report that rats or mice exposed to CUMS exhibit depression-like behaviors such as anhedonia (Willner, 2005, Yalcin et al, 2008, Qiao et al, 2016. Therefore, CUMS is widely used as an experimental model of depression.…”

Relationships between affiliative social behavior and hair cortisol concentrations in semi-free ranging rhesus monkeys

“…The health benefits of affiliative social relationships are also likely related to reduced levels of circulating glucocorticoids (GCs), hormones that participate in the physiological stress response, that result from affiliative social interactions (Heinrichs et al, 2003; Shutt et al, 2007). Indeed, chronic high levels of circulating GCs can result in cardiovascular impairments, reproductive inhibition, immunosuppression (Sapolsky, 2005), and neurobiological changes such as dendritic atrophy, which is a risk factor for depression (Qiao et al, 2016). Moreover, loneliness, or perceived social isolation, is a risk factor for mental and physical health issues (Hawkley and Cacioppo, 2013).…”