T. Madsen

Glutamatergic system and the structural plasticity hypothesis are principal components for rapid and sustained antidepressant effects of novel antidepressant therapeutics. This study represents the first investigation of the structural plasticity of the hippocampus as one of the main contributed mechanisms to the sustained anti-depressive effect of ketamine. Flinders Sensitive Line (FSL) and Flinders Resistant Line (FRL) rats were given a single intraperitoneal injection of ketamine (15 mg/kg) or saline 7 days before perfusion-fixed. The optical fractionator method was used to estimate the total number of neurons in the granular cell layer. Microvessel length in the molecular layer of DG was evaluated with global spatial sampling method. By use of the physical disector method, the number of synapses was estimated. The volume of the hippocampus was larger in the FRL-vehicle rats compared with FSL-vehicle group and in FSL-ketamine versus FSL-vehicle rats (P < 0.05). The number of non-perforated synapses was significantly higher in the FSL-ketamine versus FSL-vehicle group, (P = 0.01). A significant effect of ketamine on enhancement of the number of neurons in DG in FSL rats was observed (P = 0.01). The total length of the microvessels 1 week after ketamine treatment in the FSL rats significantly increased (P  < 0.05). Our results indicate that neurovascular changes of hippocampus could be one of the possible mechanisms underlying the sustained antidepressant effect of ketamine by reversing alteration of the number of the excitatory synapses, neuronal number and length of the microvessels in the hippocampus.

Ardalan, M., Wegener, G., Polsinelli, B., Madsen, T. M., & Nyengaard, J. R. (2016). Neurovascular Plasticity of the Hippocampus One Week after a Single Dose of Ketamine in Genetic Rat Model of Depression. Hippocampus. http://dx.doi.org/10.1002/hipo.22617
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