In vivo regulation of precursor cells in the subventricular zone of adult rat brain by thyroid hormone and retinoids.

The mature central nervous system contains precursor cells in the subventricular zone of the lateral ventricle. In this study we examined the possibility to affect fate of precursor cells through exogenous manipulations. The results indicate that administration of thyroid hormone and retinoic acid increases the expression of Ki67, a nuclear antigen associated with cell proliferation, and of nestin, a marker protein for precursor cells in the subventricular zone of adult male rats. Moreover, retinoic acid increases polysialated-neural cell adhesion molecules (PSA-NCAM)-immunoreactivity. These data suggest that nuclear receptor ligands are potential candidates for fate determination of precursor cells in the subventricular zone also in the adult brain.

Further evidence for a role of nitric oxide in experimental allergic encephalomyelitis: aminoguanidine treatment modifies its clinical evolution.

The role of nitric oxide (NO) in inflammatory/demyelinating diseases is undergoing extensive investigation as a potential target for therapeutic intervention. However, interference with NO production has resulted in contrasting effects on the development of experimental allergic encephalomyelitis (EAE), the most widely used experimental model for multiple sclerosis (MS). Purpose of this paper was both the analysis of the individual clinical evolution of EAE induced in Lewis female rats by active immunisation and the evaluation of the effect of treatment with aminoguanidine, a selective inhibitor for the inducible isoform of nitric oxide synthase (iNOS). In our experimental model, relapse occurred in 66% of animals. Aminoguanidine treatment, started 3 days before immunisation, guaranteed a complete recovery from the acute phase and a delayed, milder relapse. Moreover, 79 days after immunisation inflammatory cellular infiltrates in the spinal cord were reduced. These data further support the involvement of NO in EAE evolution.

Regulation of CCK mRNA expression in the rat brain by stress and treatment with sertraline, a selective serotonin re-uptake inhibitor.

In this paper, we have investigated the regulation of CCK mRNA expression in the brain after restraint stress with and without long-term treatment with the selective serotonin reuptake inhibitor sertraline. Stress alone increases CCK mRNA levels in the hippocampus, whereas no changes were found in the cerebral cortex, amygdaloid complex and thalamus. CCK mRNA expression decreases in the hippocampus, increases in the thalamus and was not modified in the cerebral cortex and amygdaloid complex after sertraline alone. CCK mRNA content was unchanged in all investigated areas after stress plus sertraline compared to control rats.

Is neuronal nitric oxide involved in adjuvant-induced joint inflammation?

Several reports have described a role of macrophagic, endothelial and synoviocytal nitric oxide (NO) in inflammation, immunity and sensory processes in joint diseases. In view of the role of the peripheral nervous system in arthritis and owing to the presence of NO-producing neurons in primary sensory neurons, we have investigated the possible role of neuronal NO during adjuvant-induced joint inflammation in rats. Neural nitric oxide synthase production in sensory ganglia and the spinal cord was investigated by in situ hybridization and immunocytochemistry. Neuronal NO synthase mRNA expression and neuronal NO synthase immunoreactivity increased in lumbar dorsal root ganglia in arthritic rats compared to those of normal rats, whereas neuronal NO synthase mRNA expression decreased in lamina X and lamina I-II of the lumbar spinal cord. The administration of the selective neuronal NO synthase inhibitor 7-nitro indazole, reduced the joint inflammation, whereas the administration of the inducible NO synthase selective inhibitor, aminoguanidine, had no effect on inflammation when administered daily from the third day after adjuvant. These findings could indicate a role for neural NO in adjuvant arthritis.

Dopamine receptors in the striatum of rats exposed to repeated restraint stress and alprazolam treatment.

Stress-related behaviors are accompanied by modification of a large number of neurotransmitters in the brain. Moreover, the binding to GABA(A) receptors does not account for all the effects of benzodiazepines. In this study we investigated the effect of repeated restraint stress and alprazolam treatment (1 mg/day os) on dopamine receptors (Bmax and Kd) in the striatum of adult rats by means of quantitative receptor autoradiography. After chronic restraint stress dopamine D1 receptors (Bmax value) decreased in the accumbens nucleus, whereas dopamine D2 receptors were not modified in any investigated area. After alprazolam treatment, a considerable increase in both dopamine D1 and D2 receptors in the striatum was observed. Chronic immobilization stress together with alprazolam treatment re-established dopamine D1 receptor density to control values in the accumbens nucleus and olfactory tubercle, whereas it resulted in an increase in dopamine D2 receptors comparable to that elicited by alprazolam treatment alone.

Proliferation and phenotype regulation in the subventricular zone during experimental allergic encephalomyelitis: in vivo evidence of a role for nerve growth factor.

Proliferating cells in the subventricular zone (SVZ) of adult rat brain could provide a source of cells for repair attempts during degenerative diseases. However, very few reports dealt with the spontaneous regulation of this cell population during experimental conditions. In this paper, we describe an increase in the proliferation activity in the SVZ during experimental allergic encephalomyelitis, a demyelinating disease widely used as an experimental model for human multiple sclerosis. Moreover, p75(LNGFR)-immunoreactive elements in the SVZ were larger in experimental allergic encephalomyelitis compared with control groups, and they also showed multiple and branched elongations. Finally, a selective uptake of 125I-nerve growth factor was observed in the SVZ in neonatal rats, and positive elements migrated in the corpus callosum within a few days. These data indicate that cell populations in the SVZ are regulated during inflammatory conditions and degenerative diseases involving oligodendrocytes and neurotrophins, including nerve growth factor, could participate in these phenomena.

Regulation of glutamic acid decarboxylase mRNA expression in rat brain after sertraline treatment.

We now investigated the effect of chronic treatment with sertraline on glutamic acid decarboxylase mRNA expression in different rat brain areas by means of in situ hybridization. We found a reduced glutamic acid decarboxylase mRNA expression in the prefrontal cortex, accumbens nucleus, olfactory tubercle and reticular nucleus of the thalamus. The involvement of presynaptic modulation of gamma-amino-butyric acid transmission in the anxiolytic effect of sertraline is discussed.