The dendritic tree and brain disorders.

Dendrite morphogenesis is a complex but well-orchestrated process and includes the development of dendritic branches, forming characteristic dendrite arbors, and dendritic spines, allowing neurons to communicate with each other. Various studies report that many neuropsychiatric disorders are characterized by dendritic and synaptic pathology, including abnormal spine density and morphology, synapse loss, and aberrant synaptic signaling and plasticity. In this review, we discuss dendrite development and branching, and in specific, morphology, cytoskeletal architecture, and how the complexity of the dendrite tree and its functional capabilities are altered in various brain disorders. Identifying and understanding these changes in dendrite morphology are essential for understanding brain function in normal and disease states.

Antidepressant treatments regulate matrix metalloproteinases-2 and -9 (MMP-2/MMP-9) and tissue inhibitors of the metalloproteinases (TIMPS 1-4) in the adult rat hippocampus.

Antidepressants induce structural remodeling in the adult hippocampus, including changes in dendritic arbors, axonal sprouting, neurogenesis, and endothelial cell proliferation. Such forms of structural plasticity take place in the context of the extracellular matrix environment and are known to be regulated by matrix metalloproteinases (MMPs), in particular MMP-2/9, and their endogenous regulators, the tissue inhibitors of the metalloproteinases (TIMPs 1-4). Given the hippocampal structural remodeling associated with antidepressant treatments, we hypothesized that antidepressants may regulate the expression and activity of MMP-2/9 and TIMPs 1-4. The influence of distinct classes of antidepressants, namely, electroconvulsive seizure, fluoxetine, tranylcypromine, and desipramine, on the gene expression of MMP-2, MMP-9, and TIMPs 1-4 in the hippocampus was determined using radioactive in situ hybridization. In addition, zymography studies addressed the regulation of the gelatinase activity of MMP-2/9 following acute and chronic antidepressant administration. We observed that acute and chronic ECS differentially regulate the transcript levels of MMP-2/9 and TIMPs 1-4 and also increase gelatinase activity in the hippocampus. Acute and chronic pharmacological antidepressants on the other hand differentially alter the expression of the TIMPs without any observed effect on hippocampal MMP-2/9 expression or activity. These findings raise the possibility that extracellular matrix modifying enzymes and their endogenous regulators may serve as targets for antidepressant treatments and suggests the possibility that they may contribute to antidepressant-mediated structural plasticity in the hippocampus.

Depletion of norepinephrine decreases the proliferation, but does not influence the survival and differentiation, of granule cell progenitors in the adult rat hippocampus.

The dentate gyrus region retains the ability to generate neurons throughout adulthood. A few studies have examined the neurotransmitter regulation of adult hippocampal neurogenesis and have shown that this process is regulated by serotonin and glutamate. Given the strong noradrenergic innervation of the adult hippocampus and the ability of norepinephrine to influence proliferation during development, we examined the influence of norepinephrine on adult hippocampal neurogenesis. Our study indicates that depletion of norepinephrine by the selective noradrenergic neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromo benzylamine hydrochloride (DSP-4), results in a 63% reduction in the proliferation of dentate gyrus progenitor cells identified through 5-bromo-2'-deoxyuridine (BrdU) labelling. In contrast, the survival of BrdU-positive cells labelled prior to treatment with DSP-4 is not influenced by norepinephrine depletion. The differentiation of BrdU labelled progenitors into neurons or glia was also not sensitive to noradrenergic depletion. These results indicate that the proliferation, but not the survival or differentiation, of adult hippocampal granule cell progenitors is affected by norepinephrine depletion.