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The entire shellfish farming sector is negatively affected by heat waves. Predictive models show that while heat waves are not predicted to exceed 28 °C in the northern Adriatic Sea over the coming decades, their duration will increase to periods of up to 30 days. Knowledge regarding the effects of heat waves on bivalves at physiological and molecular level is still limited. This study attempted to simulate what will happen in the future in Pacific oysters exposed to prolonged heat waves, assessing morphometric and physiological indices, and investigating the expression level of a number of genes, including the chaperone heat shock proteins HSP70, HSP72 and HSP90, and the factor P53. A state of stress in the heat wave-exposed animals was found, with loss of body weight and energy resources: despite showing a higher clearance rate, these animals were unable to absorb the nutrients required to maintain homeostasis, as well as demonstrating an alteration in hemolymphatic AST activity, total calcium and magnesium concentration. mRNA levels of all examined genes increased in response to thermal stress, with long-term overexpression, activating cell stress defense mechanisms and modulating the cycle cell. The results of this study indicate that heat waves affect oyster welfare, with consequences for the productivity of the sector due to the lack of salable products.

Neurogenesis impairment is considered a major determinant of the intellectual disability that characterizes Down syndrome (DS), a genetic condition caused by triplication of chromosome 21. Previous evidence obtained in the Ts65Dn mouse model of DS showed that the triplicated gene APP (amyloid precursor protein) is critically involved in neurogenesis alterations. In particular, excessive levels of AICD (amyloid precursor protein intracellular domain) resulting from APP cleavage by gamma-secretase increase the transcription of Ptch1, a Sonic Hedgehog (Shh) receptor that keeps the mitogenic Shh pathway repressed. Previous evidence showed that neonatal treatment with ELND006, an inhibitor of gamma-secretase, reinstates the Shh pathway and fully restores neurogenesis in Ts65Dn pups. In the framework of potential therapies for DS, it is extremely important to establish whether the positive effects of early intervention are retained after treatment cessation. Therefore, the goal of the current study was to establish whether early treatment with ELND006 leaves an enduring trace in the brain of Ts65Dn mice. Ts65Dn and euploid pups were treated with ELND006 in the postnatal period P3-P15 and the outcome of treatment was examined at ~ one month after treatment cessation. We found that in treated Ts65Dn mice the pool of proliferating cells in the hippocampal dentate gyrus (DG) and total number of granule neurons were still restored as was the number of pre- and postsynaptic terminals in the stratum lucidum of CA3, the site of termination of the mossy fibers from the DG. Accordingly, patch-clamp recording from field CA3 showed functional normalization of the input to CA3. Unlike in field CA3, the number of pre- and postsynaptic terminals in the DG of treated Ts65Dn mice was no longer fully restored. The finding that many of the positive effects of neonatal treatment were retained after treatment cessation provides proof of principle demonstration of the efficacy of early inhibition of gamma-secretase for the improvement of brain development in DS., Highlights • Neonatal inhibition of gamma-secretase has long-term effects in a Down syndrome model. • Treatment induces long-term restoration of hippocampal neurogenesis and cellularity. • Treatment induces long-term restoration of functional connectivity. • Treatments with gamma-secretase inhibitors may be exploited for Down syndrome.

Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been identified in a neurodevelopmental disorder characterized by early-onset intractable seizures, severe developmental delay, intellectual disability, and Rett's syndrome-like features. Since the physiological functions of CDKL5 still need to be elucidated, in the current study we took advantage of a new Cdkl5 knockout (KO) mouse model in order to shed light on the role of this gene in brain development. We mainly focused on the hippocampal dentate gyrus, a region that largely develops postnatally and plays a key role in learning and memory. Looking at the process of neurogenesis, we found a higher proliferation rate of neural precursors in Cdkl5 KO mice in comparison with wild type mice. However, there was an increase in apoptotic cell death of postmitotic granule neuron precursors, with a reduction in total number of granule cells. Looking at dendritic development, we found that in Cdkl5 KO mice the newly-generated granule cells exhibited a severe dendritic hypotrophy. In parallel, these neurodevelopmental defects were associated with impairment of hippocampus-dependent memory. Looking at the mechanisms whereby CDKL5 exerts its functions, we identified a central role of the AKT/GSK-3β signaling pathway. Overall our findings highlight a critical role of CDKL5 in the fundamental processes of brain development, namely neuronal precursor proliferation, survival and maturation. This evidence lays the basis for a better understanding of the neurological phenotype in patients carrying mutations in the CDKL5 gene., Highlights • Loss of Cdkl5 decreases survival of postmitotic granule cells. • Loss of Cdkl5 results in dendritic hypotrophy of newborn granule cells. • Loss of Cdkl5 impairs hippocampus-dependent behavior. • Loss of Cdkl5 alters the AKT/GSK-3β pathway.

CHF5074 is a nonsteroidal anti-inflammatory derivative that has been shown to inhibit β-amyloid plaque deposition and to reverse memory deficit in vivo in transgenic mouse models of Alzheimer's disease (AD). In the present in vivo study we used pre-plaque Tg2576 mice showing cognitive impairments to investigate the effects of a sub-acute treatment with CHF5074 on prefrontal cortex dialysate glutamate levels. Furthermore, the effects of CHF5074 have been compared with those induced, under the same experimental conditions, by LY450139, a potent γ-secretase inhibitor, that has been shown to inhibit brain β-amyloid production. No differences in prefrontal cortex dialysate glutamate levels were observed between control Tg2576 and wild-type animals. A sub-acute (8days) treatment with CHF5074 (30mg/kg, s.c.), LY450139 (3mg/kg, s.c.) or their respective vehicles did not modify prefrontal cortex dialysate glutamate levels. After these treatments, the injection of CHF5074 reduced, while LY450139 increased, prefrontal cortex dialysate glutamate levels in Tg2576 mice, but not in wild-type animals. These results suggest that at the dose tested CHF5074 and LY450139 differently affect cortical glutamate transmission in pre-plaque Tg2576 mice. This different neurochemical profile could be involved in the different ability of the two drugs in improving early cognitive performance in this animal model of AD.

Eicosapentaenoic acid (EPA), a fatty acid present in high amount in fish, modulates immune response and stimulates myelin gene expression. In the present paper, we investigated the effects of EPA in an established animal model for multiple sclerosis (MS): experimental autoimmune encephalomyelitis (EAE) induced in dark agouti rats. Diets supplemented either with 0.2% or 0.4% of EPA were administrated daily from the day of induction until the end of experiment. One group of rats received diet supplemented with 0.2% of EPA 10 days before induction. The control group (immunized rats) was fed with chow diet. The animals were analyzed at two different stages of the disease: during the acute phase (14 d.p.i.) and during the recovery phase (32 d.p.i.). We showed a delayed onset of clinical severity of disease in all groups of rats fed EPA-supplemented diets. This effect was associated to an increased expression of myelin proteins and an improved integrity of the myelin sheath as well as an up-regulation of FoxP3 expression in the central nervous system during the acute phase of EAE. No significant changes in T cell subsets were noted at the periphery. On the contrary, during the recovery phase of EAE, in animals assuming EPA-supplemented diet, an increase of CD4(+)CD25(+) and CD4(+)CD25(+)FoxP3(+) in peripheral lymphocytes was noted. Our results indicate that EPA-supplemented diets may provide benefits to MS patients.

Microdevices dedicated to monitor metabolite levels have recently enabled many applications in the field of cell analysis, to monitor cell growth and development of numerous cell lines. By combining the traditional technology used for electrochemical biosensors with nanoscale materials, it is possible to develop miniaturized metabolite biosensors with unique properties of sensitivity and detection limit. In particular, enzymes tend to adsorb onto carbon nanotubes and their optical or electrical activity can perturb the electronic properties. In the present work we propose multi-walled carbon nanotube-based biosensors to monitor a cell line highly sensitive to metabolic alterations, in order to evaluate lactate production and glucose uptake during different cell states. We achieve sensors for both lactate and glucose, with sensitivities of 40.1 mu A mM(-1) cm(-2) and 27.7 mu A mM(-1) cm(-2), and detection limits of 28 mu M and 73 mu M, respectively. This nano-biosensing technology is used to provide new information on cell line metabolism during proliferation and differentiation, which are unprecedented in cell biology. (C) 2011 Elsevier B.V. All rights reserved.

The distribution of galanin mRNA-expressing cells and galanin-immunoreactive (IR) cell bodies and processes was studied in the brain of mice overexpressing galanin under the PDGF-B promoter (GalOE mice) and of wild type (WT) mice, both in colchicine-treated and non-treated animals. A widespread ectopic expression of galanin (both mRNA and peptide) was found, that is when neither transcript nor peptide could be seen in WT mice, not even after colchicine treatment. However, in some regions, such as claustrum, basolateral amygdala, thalamus, CA1 pyramidal cells, and Purkinje cells only galanin mRNA could be detected. The highest levels of galanin expression were observed in the forebrain structures (the mitral cells of the olfactory bulb, throughout the cortex, granular and pyramidal cell layers of the hippocampus), in the mesencephalon (nucleus ruber), in the cerebellum (lateral cerebellar nucleus), in the pons (sensory and motor nuclei of the trigeminal nerve), within the medulla oblongata (facial, prepositus and spinal trigeminal nuclei). High densities of galanin-IR fibers were found in the axonal terminals of the lateral olfactory tract, hippocampal and presumably cerebellar mossy fiber system, in several thalamic and hypothalamic regions and the lower brain stem.

To study possible involvement of galanin in brain aging quality, we have investigated behavioral, neurochemical and morphological parameters in aged mice overexpressing galanin under the platelet-derived growth factor B promoter (GalOE mice) compared to wild-type littermates (WT mice). The behavioral analysis in the forced swim test showed that old GalOE animals spent more time in immobility compared to WT. In the activity cage test, galanin overexpression counteracted the age-induced decrease in exploratory behavior. The neurochemical analysis showed a 30% decrease in noradrenaline overflow in the cerebral cortex of WT old mice that was not present in age-matched GalOE mice. Our results indicate that overexpression of galanin can influence several behavioral and neurochemical parameters in old mice.

The term neuropeptide was advanced by de Wied and collaborators in the early seventies. At that time, they defined neuropeptides as endogenous substances synthesized in nerve cells and involved in nervous system functions. Since then, several studies have revealed that the very same 'neuropeptides' are also expressed in non-neuronal cells. It is therefore generally accepted that the original definition of these peptides was too limited and, consequently, it has recently been revised. Among the non-neuronal cells that synthesize neuropeptides are several glial cell types.

Age-related changes in glucose utilization through the TCA cycle were studied using [1-13C]glucose and 13C, 1H NMR spectroscopy on rat brain extracts. Significant increases in lactate levels, as well as in creatine/phosphocreatine ratios (Cr/PCr), and a decrease in N-acetyl-aspartate (NAA) and aspartate levels were observed in aged rat brains as compared to adult animals following glucose administration. The total amount of 13C from [1-13C]glucose incorporated in glutamate, glutamine, aspartate and GABA was significantly decreased in control aged rat brains as compared to adult brains. The results showed a decrease in oxidative glucose utilization of control aged rat brains. The long-term nicergoline treatment increased NAA and glutamate levels, and decreased the lactate levels as well as the Cr/PCr ratios in aged rat brains as compared to adult rats. The total amount of 13C incorporated in glutamate, glutamine, aspartate, NAA and GABA was increased by nicergoline treatment, showing an improvement in oxidative glucose metabolism in aged brains. A significant increase in pyruvate carboxylase/pyruvate dehydrogenase activity (PC/PDH) in the synthesis of glutamate in nicergoline-treated aged rats is consistent with an increase in the transport of glutamine from glia to neurons for conversion into glutamate. In adult rat brains, no effect of nicergoline on glutamate PC/PDH activity was observed, although an increase in PC/PDH activity in glutamine was, suggesting that nicergoline affects the glutamate/glutamine cycle between neurons and glia in different ways depending on the age of animals. These results provide new insights into the effects of nicergoline on the CNS.

The aging brain is characterized by selective neurochemical changes involving several neural populations. A deficit in the cholinergic system of the basal forebrain is thought to contribute to the development of cognitive symptoms of dementia. Attempts to prevent age-associated cholinergic vulnerability and deterioration therefore represent a crucial point for pharmacotherapy in the elderly. In this paper we provide evidence for the protective effect of nicergoline (Sermion) on the degeneration of cholinergic neurons induced by nerve growth factor deprivation. Nerve growth factor deprivation was induced by colchicine administration in rats 13 and 18 months old. Colchicine induces a rapid and substantial down-regulation of choline acetyltransferase messenger RNA level in the basal forebrain in untreated adult, middle-aged and old rats. Colchicine failed to cause these effects in old rats treated for 120 days with nicergoline 10 mg/kg/day, orally. Moreover, a concomitant increase of both nerve growth factor and brain-derived neurotrophic factor content was measured in the basal forebrain of old, nicergoline-treated rats. Additionally, the level of messenger RNA for the brain isoform of nitric oxide synthase in neurons of the basal forebrain was also increased in these animals. Based on the present findings, nicergoline proved to be an effective drug for preventing neuronal vulnerability due to experimentally induced nerve growth factor deprivation.

We have investigated with histochemical techniques the expression of peptides and other neurochemical markers in the hypothalamus and olfactory bulb of male mice, in which the genes encoding the alpha and beta thyroid hormone receptors (TRalpha1, TRbeta1 and TRbeta2) have been deleted. Thyrotropin-releasing hormone messenger RNA levels were increased in the hypothalamic paraventricular nucleus and in the medullary raphe nuclei of mutant mice lacking the thyroid hormone receptors alpha1 and beta (alpha1(-/-)beta(-/-)), as compared to wild-type mice. In contrast, galanin messenger RNA levels were lower in the hypothalamic paraventricular nucleus of mutant animals, as was galanin-like immunoreactivity in the internal layer of the median eminence. Substance P messenger RNA levels were unchanged in the medullary raphe nuclei. Thyrotropin-releasing hormone receptor messenger RNA levels were increased in motoneurons, unchanged in the subiculum, and lower in the amygdala of mutant animals. Galanin messenger RNA levels were unchanged in the hypothalamic dorsomedial and arcuate nuclei of the thyroid hormone receptor alpha1(-/-)beta(-/-) mice, as was the immunocytochemistry for oxytocin and for vasopressin in the hypothalamic paraventricular nucleus. A reduction in tyrosine hydroxylase messenger RNA levels was found in the arcuate nucleus of mutant mice. In the olfactory bulb, immunohistochemistry for calbindin and for tyrosine hydroxylase revealed a reduction in the intensity of labeling of nerve processes in the glomerular layer of thyroid hormone receptor alpha1(-/-)beta(-/-) mice. The tyrosine hydroxylase messenger RNA levels were also slightly reduced. In contrast, the levels of galanin and neuropeptide Y messenger RNA in this region were unchanged in thyroid hormone receptor alpha1(-/-)beta(-/-) mice as compared to wild-type mice. Together these studies reveal many regional and neurochemically selective alterations in neuronal phenotype of mice devoid of all known thyroid hormone receptors.

Mechanisms involved in transition from acute to chronic pain are still not well understood and our means to therapeutically influence this transition are limited. Moreover, very little is known about long-lasting consequences of prolonged exposure to painful stimuli with regard to phenotypic changes and pain experience. In this study we have analyzed long term behavioral and neurochemical effects of intradermal tail injection of heat-killed mycobacterium butyricum suspended in complete Freund's adjuvant. Calcitonin gene-related peptide (CGRP) and galanin mRNA levels were investigated in dorsal root ganglia of polyarthritic rats during the acute (21-) and the remission stage (79 days postinjection), and opioid peptide mRNAs and receptors were studied in the spinal cord. Most of the increases in peptide mRNA levels observed during the acute stage of arthritis were still present in the remission stages. Thus, CGRP and galanin mRNAs in DRGs, and opioid peptide mRNAs and opioid receptors in the spinal cord were still strongly up-regulated, when animals do not exhibit spontaneous pain behavior and inflammation. Hot-plate test in the presence of naloxone, performed in the remission stage, indicated that opiates participate in pain threshold regulation after prolonged painful condition. Finally, X-ray examination revealed a complete destruction of joint structure, thus suggesting a parallel lesion of peripheral nerve endings. These results suggest that in the remission stage of chronic joint inflammation several types of mechanisms are activated aiming at counteracting both inflammatory and neuropathic pain. Thus, opioid systems in the dorsal horn as well as galanin in DRG neurons are upregulated, both alternating pain.

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.

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.

It is well known that thyroid hormone plays a crucial role in the development and maturation of the nervous system. However, little is known about the role of thyroid hormone in the adult brain. In this short review we have dwelt on this point, with regard to the role of thyroid hormone on neuropeptide gene expression regulation in the paraventricular nucleus of the hypothalamus and in extrahypothalamic brain areas, on neurotrophin and neurotrophin receptor expression in the hippocampus and basal forebrain in basal conditions, and after neurotoxic challenges. Effects of hypothyroidism are discussed in view of a possible role of thyroid status in brain aging quality.

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 γ-aminobutyric acid transmission in the anxiolytic effect of sertraline is discussed.

In male rats, whether sexually experienced or sexually naive, the intraperitoneal administration of L-arginine (the natural substrate for nitric oxide synthase) (10, 25, 50 mg/kg) both increased the percentage of copulating in sexually naive rats and improved the indexes of sexual performance in sexually experienced rats, whereas the intraperitoneal administration of N(G)-nitro-L-arginine methyl ester (L-NAME) (a potent inhibitor of nitric oxide synthase) (10, 25, 50 mg/kg) had opposite effects. In contrast, after intracerebroventricular administration, L-arginine (25, 50, 100 microg/rat) had no effect - whether in naive or in experienced rats - whereas L-NAME completely prevented ejaculation in naive rats, at the dose of 100 microg/rat, but had no effect at all in experienced rats, up to the dose of 300 microg/rat. Finally, a direct relationship seems to exist between male copulatory performance and nitric oxide synthase activity in a discrete and defined brain area, the paraventricular nucleus of the hypothalamus: indeed, nitric oxide synthase mRNA expression in this nucleus in sexually potent rats is about twice that in sexually impotent rats. It is concluded that nitric oxide synthase is involved in the expression of male sexual activity, in spite of some inconsistencies that are hard to interpret.

An abnormal thyroid status induced morphological and neurochemical modifications in the adult brain. In this study we have analyzed the expression of enkephalin (ENK) and dynorphin (DYN) precursor mRNAs by means of in situ hybridization in the brain of hypothyroid and hyperthyroid rats. The influence of thyroid hormones on kainic acid (KA)-induced expression of ENK and DYN mRNAs in the granule cells of the dentate gyrus was also studied. Our results can be summarized as follows: (1) hypothyroidism induces an up-regulation of ENK mRNA in the granule cells of the dentate gyrus and layers V/VI of the cingulate cortex and of DYN mRNA in the granule cells of the dentate gyrus; (2) the up-regulation of ENK mRNA expression in the granule cells induced by KA is not modified by altered thyroid status; (3) in contrast, the KA injection fails to up-regulate DYN precursor mRNA expression in the granule cells of the rostral dentate gyrus of the hypothyroid rats; (4) injection of KA in hyperthyroid rats increases the expression of DYN mRNA in the granule dentate gyrus more than in euthyroid rats. The present results suggest that thyroid hormones exert an inhibitory control of expression of ENK and DYN mRNAs in selected brain areas. This effect could be directly mediated through the thyroid hormone nuclear receptor or could be secondary to changes in glutamatergic transmission in the dentate gyrus, as suggested by the profound alteration of the KA-induced expression of DYN mRNA in the dentate gyrus of hypo-and hyperthyroid rats.

This article investigates the distribution of neurotransmitters, neuropeptides, and related receptors in the vestibular nuclei complex (VNC) of the adult rat by means of immunohistochemistry, in situ hybridization, and quantitative receptor autoradiography. The entire complex proves to be rich in muscarinic receptors and it shows a high density of imipramine and benzodiazepine binding sites. Peptidergic neurons and a few positive fibers are described in the caudal part of the VNC. In particular, the medial vestibular nucleus contains a number of neurons expressing both the enkephalin mRNA and peptide. This nucleus and the lateral vestibular nucleus are also rich in opiate receptors. Substance P, thyrotropin releasing hormone, and neurotensin receptors are also found in the medial and in the spinal vestibular nuclei. In spite of the presence of α 2 catecholaminergic receptors, no thyrosine-hydroxylase-immunoreactive elements are seen in the caudal VNC. The possible functional meaning of these data is discussed.

A role of thyroid hormone in the regulation of neuropeptide synthesis has been demonstrated in different tissues. In this paper we investigated the vasoactive intestinal peptide (VIP) mRNA expression by means of in situ hybridization in several brain areas of hypo- and hyperthyroid adult rats. Neither hypo- nor hyperthyroidism modified the VIP mRNA levels in the thalamus and in the hypothalamic suprachiasmatic nucleus. In contrast, in the anterior cingulate and frontoparietal motor cortex of hypothyroid rats there was a marked increase in the signal for VIP mRNA per cell, but the number of VIP expressing neurons did not change. These data indicate that also central VIP synthesis can be influenced by the levels of circulating thyroid hormone, but that this effect is confined to specific areas and cell populations of the brain.

The peripheral territories of sheep trigeminal neurons which send their central process to the brainstem through the oculomotor nerve were investigated by the use of fluorescent tracers in double-labeling experiments. For this purpose Diamidino yellow (DY) injection into the oculomotor nerve was combined with Fast blue (FB) injection either into the extraocular muscles (EOMs), or the cornea, or the superior eyelid. Double-labeled DY + FB cells were found in the ophthalmic region of the trigeminal ganglion in addition to single-labeled DY or FB cells. The DY and DY + FB-labeled trigeminal cells were analysed immunocytochemically for their content of substance P (SP)-, calcitonin gene-related peptide (CGRP)-, and cholecystokinin-8 (CCK-8)-like. All single-labeled DY cells showed SP-, CGRP- or CCK-8-like immunoreactivity. Double-labeled DY + FB neurons innervating the EOMs were immunoreactive for each of the three peptides, whereas double-labeled neurons supplying the cornea were only CGRP-like positive. The findings suggest that, in the sheep, trigeminal neurons which send their process centrally through the oculomotor nerve supply the EOMs, the cornea, and the superior eyelid and contain neuropeptides which are usually associated with pain sensation.

Typical and atypical neuroleptic drugs show several clinical and behavioral effects, possibly related to the different anatomical sites of the action in the mesolimbocortical or mesostriatal dopaminergic systems. Because of the interaction between dopamine (DA) and neurotensin (NT) in the target areas of these systems, and in order to study if the different action of typical and atypical neuroleptic drugs could be related to a modification of the DA/NT balance, we investigated DA2 and NT receptor modifications--by means of quantitative receptor autoradiography--after chronic treatment with low dosage of haloperidol, chlorpromazine, thioridazine and clozapine. We described a decrease of NT receptor density in the target areas of the mesolimbocortical system produced by all the treatments. This effect does not match with DA2 receptor modifications. On the contrary, the block of DA transmission obtained by high dosage of haloperidol induces an increase of NT receptor density. Our results further demonstrate the regulation of NT transmission by DAergic drugs.

In rats the effects of chronic treatment with thioridazine (5 mg/kg orally administered for 22 days) were studied by means of behavioural supersensitivity to apomorphine and by means of dopamine (DA) receptors quantitative autoradiography. Locomotion and stereotypies induced by apomorphine increased after thioridazine chronic administration, whereas grooming behaviour decreased. Autoradiographic data showed an increase in DA receptors density both in the striatum and in the olfactory tubercle, to which the increase in stereotypies and locomotion could be respectively attributed. DA receptors increased also in the medial and dorsal frontal cortex. Moreover a decrease in DA receptors density appeared in the nucleus accumbens septi and in the lateral frontal cortex. Receptors decrease found in these regions might be associated with thioridazine-induced chronic inactivation of A10 DA neurons, to which the antipsychotic effect of the drug is attributed.

Most of the biochemical, physiological and behavioural events in living organisms show diurnal fluctuations, normally synchronized with 24-h environmental rhythms, such as the light-dark cycle. The suprachiasmatic nucleus (SCN) of the hypothalamus is considered to be a pacemaker of the circadian rhythms in several mammals. The light-dark cycle is the primary synchronizing agent for many of the circadian rhythms which are regulated by the SCN. The photic information reaches the SCN also through a neuropeptide Y(NPY)-like immunoreactive pathway from the ventro-lateral geniculate nucleus. We found that in 12-h-dark and 12-h-light housed rats the NPY-like immunoreactive innervation of the ventro-lateral part of the SCN shows a 24 h rhythm with values rising gradually during the light phase and falling during the dark phase. Besides this rhythm, we found two peaks corresponding to the switching on and switching off of the light. The average level of NPY-like immunoreactivity, as assessed by means of semiquantitative immunocytochemistry and expressed in ‘arbitrary units’, is reduced in rats housed in total darkness for 2 weeks. These results confirm the physiological role of NPY in the timing of the circadian activity of the SCN.

A method has been developed to integrate rostrocaudal information from morphometrically characterized 5-HT nerve cell groups visualized by means of the indirect immunofluorescence technique in single coronal sections of the neuroaxis. The present method has been applied to the 5-HT positive cells of the medulla oblongata of the rat. 5-HT cell body and cell group parameters were measured by the use of a semiautomatic image analyzer (Kontron, MOP AMO 2) plugged into an Apple II computer. The density distribution of 5-HT positive cells was also studied by dividing the area analyzed into unitary squares (about 120 × 120 μm) and then by considering the number of 5-HT cells falling in each of these squares. The existence of a 5-HT cell group was determined by testing the randomness of the 5-HT profiles per unitary square. The entire population of 5-HT positive cells as well as the 5-HT cell groups were described in terms of gravity center coordinates, mean maximal diameter and homogeneity index. A rostrocaudal representation of the gravity centers and of the dispersion of the 5-HT nerve cell groups around them provided an exact three-dimensional description of the respective locations of the 5-HT cell groups within the medulla oblongata. These methods can be applied to all types of transmitter-identified cell groups and at any level of the neuroaxis.

The main serotoninergic groups have been described in the midbrain raphe; in the region of the solitary tract, serotonin (5-HT) has been localized in varicose processes and terminals. This study shows the presence of serotoninergic neurons located in the medial nuclei of the solitary tract of intracisternally injected rats, and describe the mapping, the morphological and morphometrical characteristics of these neurons in young and old rats. In old rats the number of these neurons is approximately double the amount detected in young rats. The suggestions on the functional meaning of these findings are discussed.

The effect of GM1 ganglioside on the recovery of nigro-strital dopaminergic neurons was studied in rats after unilateral hemitransection. We find that repeated administration of GM1 significantly increased the HVA content, the tyrosine hydroxylase activity and the tyrosine hydroxylase-related immunofluorescence in the striatum ipsilateral to the lesion. Futhermore, GM1 reduced the sensitivity of lesioned rats to apomorphine. The data comparable with the view that a functional dopaminergic reinnervation of the striatum is facilitated by GM1 treatments after hemitransection.