Search

Recent hypotheses suggest that changes in neuronal structure and connectivity may underlie the etiology of depression. The medial prefrontal cortex (mPFC) is affected by depression and shows neuronal remodeling during adulthood. This plasticity may be mediated by the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), which is intensely expressed in the adult mPFC. As the expression of PSA-NCAM is increased by serotonin in other cerebral regions, antidepressants acting on serotonin reuptake may influence PSA-NCAM expression and thus counteract the effects of depression by modulating neuronal structural plasticity. Using immunohistochemistry, we have studied the relationship between serotoninergic fibers and PSA-NCAM expressing neurons in the adult rat mPFC and the expression of serotonin receptors in these cells. The effects of fluoxetine treatment for 14 days on mPFC PSA-NCAM expression have also been analyzed. Although serotoninergic fibers usually do not contact PSA-NCAM immunoreactive neurons, most of these cells express 5-HT3 receptors. In general, chronic fluoxetine treatment induces significant increases in the number of PSA-NCAM immunoreactive neurons and in neuropil immunostaining and coadministration of the 5-HT3 antagonist ondansetron blocks the effects of fluoxetine on PSA-NCAM expression. These results indicate that fluoxetine, acting through 5-HT3 receptors, can modulate PSA-NCAM expression in the mPFC. This modulation may mediate the structural plasticity of this cortical region and opens new perspectives on the study of the molecular bases of depression.Neuropsychopharmacology (2007) 32, 803–812. doi:10.1038/sj.npp.1301183; published online 9 August 2006 [ABSTRACT FROM AUTHOR]

Complete removal of synaptic zinc by the chelator dietyldithiocarbamate (DEDTC; 500 mg/kg i.p.) in rat was followed by convulsive behaviour including wet dog shakes alternating immobility. Histological analysis 1 day after DEDTC administration detected expression of heat shock protein in the hippocampus restricted to hilar cells. These cells colocalize the marker for neurons and the glutamate receptor GluR2/3 showing that they are excitatory neurons. Additionally, they projected to the contralateral dentate gyrus. Therefore, they correspond to hilar mossy cells. These data show that the synaptic zinc has a role in normal hippocampus avoiding overexcitation, that would impair functionality even in absence of pathological or exoexcitotoxic phenomena. [Copyright &y& Elsevier]

In the olfactory glomeruli of the rat olfactory bulb, there is a population of periglomerular cells (PG) that contains the neuronal isoform of the nitric oxide synthase (nNOS). To date, these PG have not been characterized neurochemically and it has not been determined whether they are type 1 (GABAergic PG that receive synaptic contacts from the olfactory axons) or type 2 PG (non-GABAergic PG that do not receive synapses from the olfactory axons). Combining pre-embedding NADPH-diaphorase histochemistry and post-embedding immunoperoxidase detection of GABA, we demonstrate that nNOS-containing PG are GABAergic and therefore, belong to the type 1 PG. The possible actions of nitric oxide in the olfactory glomeruli are discussed. [Copyright &y& Elsevier]

There is a dramatic increase in the number of lightly immunoreactive calretinin cells in the granular layer of the dentate gyrus of the mouse hippocampus 1 day after excitotoxic injury using kainic acid combined with the zinc chelator diethyldithiocarbamate. At 7 days after treatment, these cells are strongly immunoreactive for calretinin and for the polysialated form of the glycoprotein neural cell adhesion molecule (PSA-NCAM). The reexpression of calretinin and PSA-NCAM after treatment corresponds well with the loss of input from the damaged hilar mossy cells. These cells could be considered immature granule cells since they are immunoreactive to markers for immature cells such as PSA-NCAM, and are not immunoreactive to calbindin D28k and neuronal nuclear specific protein NeuN (present in mature granule cells), or GABA (present in interneurons). Ultrastructural analysis of these cells indicates that they are immature. Labelling of cell proliferation with 5-bromo-2'-deoxyuridine (BrdU) shows that by day 1 no calretinin immunoreactive cell of the dentate gyrus corresponds to newly generated cells. By day 7 only 6% of the calretinin immunoreactive cells in the dentate gyrus are marked for BrdU. Our data indicate that the CR/PSA-NCAM immunoreactive cells of the dentate gyrus, in spite of their immature characteristics, are not the products of reactive neurogenesis. These cells could represent a reservoir of pre-existing not completely differentiated granule cells that react to damage.

The distribution of vasoactive intestinal polypeptide (VIP)-immunopositive elements was analyzed in the olfactory bulb (OB) of the Western European hedgehog (Erinaceus europaeus) under light and electron microscopy. The immunoreactivity appeared in an abundant population of periglomerular cells of the glomerular layer, in interneurons of the external plexiform layer, and in a restricted group of deep short-axon cells of the internal plexiform layer, the granule cell layer and the white matter. In the glomerular layer, VIP-containing periglomerular cells constituted a population of non-GABAergic neurons and did not receive synapses from olfactory axons. In the EPL, VIP-immunoreactivity appeared in a morphologically heterogeneous population of GABAergic interneurons, most of them identified as satellite cells and Van Gehuchten cells. These interneurons exerted an abundant and selective innervation of the somata, primary and secondary dendrites of the principal mitral and tufted cells, but did not contact granule cells. Perisomatic innervation of the principal cells followed two different patterns. The first included 'normal' basket-like arrangements of VIP-containing varicosities surrounding the somata of mitral and tufted cells. In the second, a set of satellite cells gave rise to short dendritic shafts that embraced the somata of principal cells in an 'exuberant' basket-like arrangement. These two morphological patterns of perisomatic innervation of principal cells were correlated with a neurochemical specificity of the target. In this sense, the 'exuberant' basket-like structures were always found surrounding a subpopulation of principal cells that did not contain the calcium-binding protein parvalbumin (PV). By contrast, they were never found surrounding the subpopulation of PV-containing principal cells, which only showed 'normal' basket-like structures. This study provides new data on the connectivity and neurochemical features of the hedgehog olfactory bulb and suggests that the olfactory circuits in this species are more complex than those described in other mammals.