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Motoneuron phenotype in the spinal cord is regulated by an intrinsic genetic program, extrinsic environmental signals and target-derived molecules. Axonal lesions trigger a phenotype switch to foster repair phenomena and axonal re-growth. We have investigated the influence of the long-term treatment with thyroid hormone and all trans retinol palmitate (RA) on motoneuron phenotype and spinal cord reaction to axotomy in adult male rats. Neurochemical markers, investigated by in situ hybridization and immunocytochemistry, included choline acetyltransferase (ChAT), calcitonin gene-related peptide (CGRP) and neurotrophin low affinity receptor p75. Treatment was administered for 56 days and then mid-thigh sciatic axotomy was performed on a number of animals from each experimental groups; the rats were examined 9 days after surgery. The results indicate that: (1) Number and size of ChAT-immunoreactive neurons in the lumbar tract of the spinal cord was reduced in hypothyroid compared to control rats, whereas steady-state level of ChAT mRNA in labelled motoneurons failed to be modified by hypo and hyperthyroidism, but was increased by RA administration; (2) none of the administered treatments did alter CGRP mRNA level, whereas all of them influenced the axotomy-induced changes of motoneuron phenotype; (3) in hyperthyroid rats ChAT mRNA level of lumbar motoneurons not reduced homolateral to lesion while the number of ChAT-IR profiles was pronouncedly reduced; (4) up-regulation of p75 induced by peripheral nerve lesion was reduced in RA-treated rats. These data indicate that the motoneuron phenotype is regulated by transcription factors, which also play a role in phenotype switch regulation after axotomy.

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., (Copyright 1999 Published by Elsevier Science B.V.)

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.

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.

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.

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.