In addition to regulation of neurogenesis, the complexity of the dendritic arbour of neurons is altered by stress and antidepressant treatments. The formation of spine synapses or synaptogenesis is a key form of neuroplasticity, and represents a fundamental characteristic of neurons. Synaptogenesis is a structural change at a subcellular level that takes place in response to synaptic activity, and provides a mechanism for processing and incorporating new information that can be used to make the appropriate, future adaptive response (). Cellular models of learning and memory, such as long-term potentiation (LTP), have been used to study the mechanisms underlying synaptogenesis. Increased neuronal activity leads to insertion of glutamate receptors and maturation of spine synapses [29
Figure 2. Model for activity-dependent stimulation of synaptogenesis and spine formation. Synaptic activity and increased glutamate transmission can lead to increased synapse formation and spine density. This occurs through insertion of glutamate-AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (more ...)
The dendrite branches of neurons can be visualized by using a number of approaches, including Golgi impregnation or by filling cells with a dye that diffuses throughout the processes. These approaches allow for analysis of the number and length of dendrite branch points, and even the number of spines, the points of synaptic contact between neuronal processes.
The complexity of neuronal dendrites and number of spine synapses is markedly decreased by chronic stress exposure. This includes decreased number and length of apical dendrites in the CA3 pyramidal cell layer of the hippocampus and layer V pyramidal neurons of the PFC [30
]. Reductions of dendrites and spines are observed in the PFC after as little as 7 days of restraint stress [32
], and have been associated with depressive behaviours after exposure to chronic unpredictable stress (CUS) [33
]. These studies support the possibility that decreased dendrite complexity contributes to the reduced volume of hippocampus and PFC reported in depressed patients.
The role of BDNF in the regulation of dendrite complexity and spine formation has also been examined in mutant mice. A knockin of the BDNF Met polymorphism has been developed, and studies show that expression of even a single copy of this human variant decreases the number and length of apical dendrites of CA3 pyramidal neurons, similar to the effects of chronic stress on dendrites [23
]. BDNF heterozygous deletion mutant mice also have reduced CA3 apical dendrites [23
]. Further studies will be required to determine whether reduced BDNF is responsible for the dendritic atrophy caused by chronic stress, but the current findings are consistent with this hypothesis.
Although antidepressant medications increase the expression of BDNF, there is little evidence that these agents reverse the dendrite atrophy caused by chronic stress. There is one study demonstrating that an atypical antidepressant, tianeptine, reverses the effects of chronic stress on atrophy of CA3 pyramidal neurons [34
]. The lack of evidence for antidepressant reversal could reflect the technical challenges and time commitment required to conduct these difficult studies. In addition, it is possible that although BDNF expression is increased, typical antidepressant treatments do not increase BDNF release, which is required for increased synaptogenesis [23