Seizure susceptibility to neurological insults, including chemical convulsants, is age-dependent and most likely reflective of overall differences in brain excitability. The molecular and cellular mechanisms underlying development-dependent seizure susceptibility remain to be fully understood. Because the mTOR pathway regulates neurite outgrowth, synaptic plasticity and cell survival, thereby influencing brain development, we tested if exposure of the immature brain to the mTOR inhibitor rapamycin changes seizure susceptibility to neurological insults. We found that inhibition of mTOR by rapamycin in immature rats (3 to 4 weeks old) increases the severity of seizures induced by pilocarpine, including lengthening the total seizure duration and reducing the latency to the onset of seizures. Rapamycin also reduces the minimal dose of pentylenetetrazol (PTZ) necessary to induce clonic seizures. However, in mature rats, rapamycin does not significantly change the seizure sensitivity to pilocarpine and PTZ. Likewise, kainate sensitivity was not significantly affected by rapamycin treatment in either mature or immature rats. Additionally, rapamycin treatment down-regulates the expression of potassium-chloride cotransporter 2 (KCC2) in the thalamus and to a lesser degree in the hippocampus. Pharmacological inhibition of thalamic mTOR or KCC2 increases susceptibility to pilocarpine-induced seizure in immature rats. Thus, our study suggests a role for the mTOR pathway in age-dependent seizure susceptibility.

Cholecystokinin (CCK) is a neuropeptide widely distributed in the mammalian brain. This peptide regulates many physiological functions and behaviors, such as cardio-respiratory control, thermoregulation, nociception, feeding, memory processes and motivational responses, and plays a prominent role in emotional responses including anxiety and depression. CCK-expressing brain regions involved in these functions remain unclear and their identification represents an important step towards understanding CCK function in the brain. The basolateral amygdala is strongly involved in emotional processing and expresses high levels of CCK. In this study we examined the contribution of CCK expressed in this brain region to emotional responses in mice. To knockdown CCK specifically in the basolateral amygdala, we used stereotaxic delivery of recombinant adeno-associated viral vectors expressing a CCK-targeted shRNA. This procedure efficiently reduced CCK levels locally. shCCK-treated animals showed reduced levels of anxiety in the elevated plus-maze, and lower despair-like behavior in the forced swim test. Our data demonstrate that CCK expressed in the basolateral amygdala represents a key brain substrate for anxiogenic and depressant effects of the peptide. The study also suggests that elevated amygdalar CCK could contribute to panic and major depressive disorders that have been associated with CCK dysfunction in humans.

Absence seizures are common in the stargazer mutant mouse. The mutation underlying the epileptic phenotype in stargazers is a defect in the gene encoding the normal expression of the protein stargazin. Stargazin is involved in the membrane trafficking and synaptic targeting of AMPA receptors (AMPARs) at excitatory glutamatergic synapses. Thus, the genetic defect in the stargazer results in a loss of AMPARs and consequently, excitation at glutamatergic synapses. Absence seizures are known to arise in thalamocortical networks. In the present study we show for the first time, using Western blot analysis and quantitative immunogold cytochemistry, that in the epileptic stargazer mouse, there is a global loss of AMPAR protein in nucleus reticularis (RTN) and a selective loss of AMPARs at corticothalamic synapses in inhibitory neurons of the RTN thalamus. In contrast, there is no significant loss of AMPARs at corticothalamic synapses in excitatory relay neurons in the thalamic VP region. The findings of this study thus provide cellular and molecular evidence for a selective regional loss of synaptic AMPAR within the RTN that could account for the loss of function at these inhibitory neuron synapses, which has previously been reported from electrophysiological studies. The specific loss of AMPARs at RTN but not relay synapses in the thalamus of the stargazer, could contribute to the absence epilepsy phenotype by altering thalamocortical network oscillations. This is supported by recent evidence that loss of GluA4 (the predominant AMPAR-subtype in the thalamus), also leads to a specific reduction in strength in the cortico-RTN pathway and enhanced thalamocortical oscillations, in the Gria4(-/-) model of absence epilepsy. Thus further study of thalamic changes in these models could be important for future development of drugs targeted to absence epilepsy.

L-arginine, a semi-essential amino acid, can be metabolized to form a number of bioactive molecules. Nitric oxide (NO), generated by NO synthase (NOS) from L-arginine, has been strongly implicated in the aging process. Agmatine, decarboxylated arginine, regulates the production of NO and other metabolites of L-arginine, modulates behavioural function, and has anti-inflammatory and neuroprotective effects. The present study investigated whether agmatine supplementation could improve behavioural function in aged male Sprague-Dawley rats, and could attenuate age-related changes in NOS activity and protein expression in memory-related structures. Aged rats treated with saline displayed significantly reduced exploratory activity and impaired spatial reference and working memory and object recognition memory. Agmatine (40 mg/kg) administered intraperitoneally significantly improved spatial working memory and object recognition memory in aged rats, suppressed age-related elevation in total NOS activity, and restored endothelial NOS protein to the normal level. However, agmatine supplementation was unable to improve exploratory activity and spatial reference learning and memory in aged rats. These findings suggest that exogenous agmatine selectively improves behavioural function in aged rats under the present experimental condition, and merit future investigation of its therapeutic potential in cognitive decline during aging.

Our previous studies have demonstrated that application to the tooth pulp of the inflammatory irritant mustard oil (MO) induces medullary glutamate release and central sensitization in the rat medullary dorsal horn (MDH), as well as nociceptive sensorimotor responses in craniofacial muscles in rats. There is recent evidence that anticonvulsant drugs such as pregabalin that influence glutamatergic neurotransmission are effective in several pain states. The aim of this study was to examine whether systemic administration of pregabalin attenuated glutamate release in the medulla as well as these nociceptive effects reflected in increased electromyographic (EMG) activity induced by MO application to the tooth pulp. Male adult rats were anesthetized with isofluorane (1.0∼1.2%), and jaw and tongue muscle EMG activities were recorded by needle electrodes inserted bilaterally into masseter and anterior digastric muscles and into the genioglossus muscle, and also the medullary release of glutamate was assessed by in vivo microdialysis. Pregabalin or vehicle control (isotonic saline) was administered 30 min before the pulpal application of MO or vehicle control (mineral oil). Application of mineral oil to the maxillary first molar tooth pulp produced no change in baseline EMG activity and glutamate release. However, application of MO to the pulp significantly increased both the medullary release of glutamate and EMG activity in the jaw and tongue muscles for several minutes. In contrast, pre-medication with pregabalin, but not vehicle control, significantly and dose-dependently attenuated the medullary glutamate release and EMG activity in these muscles after MO application to the tooth pulp (ANOVA, p<0.05). These results suggest that pregabalin may attenuate the medullary release of glutamate and associated nociceptive sensorimotor responses in this acute inflammatory pulpal pain model, and that it may prove useful for the treatment of orofacial inflammatory pain states.

The hippocampus is required for short-term memory and contains both excitatory pyramidal cells and inhibitory interneurons. These cells exhibit various forms of synaptic plasticity, the mechanism underlying learning and memory. More recently, endocannabinoids were identified to be involved in synaptic plasticity. Our goal was to describe the distribution of endocannabinoid biosynthetic enzymes within CA1 stratum radiatum interneurons and CA3/CA1 pyramidal cells. We extracted mRNA from single interneurons and pyramidal cells and used real-time quantitative PCR to detect the presence of 12-lipoxygenase, N-acyl-phosphatidylethanolamine-specific phospholipase D, diacylglycerol lipase α, and type I metabotropic glutamate receptors, known to be involved in endocannabinoid production and plasticity. We observed that the expression of endocannabinoid biosynthetic enzyme mRNA does occur within interneurons and that it is coexpressed with type I metabotropic glutamate receptors, suggesting interneurons have the potential to produce endocannabinoids. We also identified that CA3 and CA1 pyramidal cells express endocannabinoid biosynthetic enzyme mRNA. Our data provide the first molecular biological evidence for putative endocannabinoid production in interneurons, suggesting their potential ability to regulate endocannabinoid-mediated processes, such as synaptic plasticity.

Prostaglandin (PG) F(20) is one of the major prostanoids biosynthesized by cyclooxygenases (COXs) from arachidonic acid. Although it has been reported that there is a selective surge in PGF(20) production in the hippocampus during kainic acid (KA)-induced seizure activity, the precise intra-hippocampal distribution of PGF(20) has not been elucidated due to the paucity of effective histological techniques for detecting PGs in tissues. We investigated the tissue distribution of PGF(20) in the rat hippocampus 30 min after KA injection by developing fixation and immunohistological staining methods. To detect PGF(20) directly on histological sections, we used systemic perfusion fixation with water-soluble carbodiimide fixative, followed by immersion of the brains in Zamboni's fixative. We then performed immunofluorescence staining with anti-PGF(20) antibody, with negative control experiments used to confirm the staining specificity. Definitive immunolabeling for PGF(20) was evident most markedly in pyramidal cells of the hippocampal cornu Ammonis (CA) 3 sector and neurons of the hilus in KA-treated rats. Immunolabeling for PGF(20) was also evident in granule cells of the dentate gyrus. Double immunfluorescence staining revealed that PGF(20)-immunopositive neurons expressed cytosolic phospholipases A(2), COX-2, and FP receptor. These results suggest that the major source of PGF(20) production immediately after KA injection was neurons of the hippocampal CA3 sector, hilus and dentate gyrus. These neurons exert PGF(20)-mediated functions via FP receptors in an autocrine/paracrine manner and may play pathophysiological roles in the acute phase (30 min) of excitotoxicity.

Status epilepticus (SE) induced by pilocarpine or kainate is associated with yet not systemically investigated astrocytic and vascular injuries. To investigate their possible association with neuronal damage, the changes in glial fibrillary acidic protein (GFAP), laminin and neuron-specific nuclear protein (NeuN) immunoreactivities were analyzed in rats treated with pilocarpine (380 mg/kg) or kainate (15 mg/kg), and receiving diazepam (20 mg/kg) after 10 min of SE. A different group of rats was injected with endothelin-1 (ET-1) in the caudate putamen to reproduce the changes in GFAP and laminin immunoreactivities associated with ischemia. Focal loss of GFAP immunostaining was accompanied by increased laminin immunoreactivity in blood vessels, in all the examined groups. Regression analysis revealed a significant (P < 0.01) relationship between astrocytic lesion and increased laminin immunoreactivity in the piriform cortex (Pir) of both pilocarpine (R(2)= 0.88) and kainate (R(2)= 0.94) groups of treatment. A significant relationship (P < 0.01; R(2)= 0.81) was also present in the CA3 hippocampal region of pilocarpine-treated rats. At variance, neuronal and glial lesions were significantly related (P < 0.05, R(2)= 0.74) only in the substantia nigra of pilocarpine-treated rats. The ratio between areas of GFAP and laminin changes of immunoreactivity in the ET-1 group was similar to those found in pilocarpine- and kainate-treated rats in specific brain regions, such as the hippocampal CA3 subfield, Pir and the anterior olfactory nucleus. The amygdala and submedius thalamic nucleus in the pilocarpine group, and the perirhinal and entorhinal cortices in the kainate group, also presented ischemic-like changes. These results indicate that laminin immunoreactivity is upregulated in the basal lamina of blood vessels after SE induced by pilocarpine or kainate. This phenomenon is significantly associated with lesions involving more glial than neuronal cells, in specific cerebral regions.

Several lines of evidence indicate group III metabotropic glutamate receptors (mGluRs) have systemic anti-hyperalgesic effects. We hypothesized this could occur through modulation of TRPV1 receptors on nociceptors. To address this question we performed anatomical studies to determine if group III mGluRs were expressed on cutaneous axons and if they co-localized with TRPV1. Immunostaining at the electron microscopic level demonstrated that 22% of unmyelinated axons labeled for mGluR8. Immunostaining at the light microscopic level in lumbar dorsal root ganglia (DRG) demonstrated that 80% and 28% of neurons labeled for mGluR8 or TRPV1, respectively. Of those neurons labeled for mGluR8, 25% labeled for TRPV1; of those labeled for TRPV1, 71% labeled for mGluR8. In behavior studies intraplantar injection of the group III mGluR agonist, L-AP-4 (0.1 1.0, 10.0 μM) had no effect on paw withdrawal latency (PWL) to heat in naïve rats but administration of 10 μM L-AP-4 prior to 0.05% capsaicin (CAP), significantly attenuated CAP-induced lifting/licking and reduced flinching behavior. The L-AP-4 effect was specific since administration of a group III antagonist UBP1112 (100 μM) blocked the L-AP-4 effect on CAP, resulting in behaviors similar to CAP alone. Intraplantar injection of UBP1112 alone did not result in nociceptive behaviors, indicating group III mGluRs are not tonically active. Finally, the anti-hyperalgesic effect of group III in this paradigm was local and not systemic since intraplantar administration of L-AP-4 in one hind paw did not attenuate nociceptive behaviors following CAP injection in the contralateral hind paw. Adenyl cyclase/cAMP/PKA may be the second messenger pathway linking these two receptor families because intraplantar injection of forskolin (FSK, 10 μM) reduced PWL to heat and L-AP-4 reversed this FSK effect. Taken together, these results suggest group III mGluRs can negatively modulate TRPV1 through inhibition of AC and downstream intracellular activity, blocking TRPV1-induced activation of nociceptors.

In teleost fish, sex differences in several behavioral and physiological traits have been assumed to reflect underlying sex differences in the central expression of neurotransmitter/neuromodulator-related molecules, including vasotocin (VT)/isotocin (IT), gonadotropin-releasing hormone (GnRH), and tyrosine and tryptophan hydroxylases (TH and TPH). However, the sex-dependent expression patterns of these molecules have not been fully characterized in the teleost brain. In the present study, we therefore systematically evaluated sex differences in their expression in the medaka (Oryzias latipes) brain. The most prominent sex difference was observed in vt expression in the nucleus posterior tuberis (NPT) and the posterior part of the nucleus ventral tuberis (NVT) in the hypothalamus, where the expression was completely male-specific. Male-biased expression of gnrh1, tph1, and tph2 was also evident in the supracommissural and posterior nuclei of the ventral telencephalic area (Vs/Vp), medial nucleus of the dorsal telencephalic area (Dm), and thalamic dorsal posterior nucleus (DP), respectively. In contrast, the overall expression levels of it and gnrh3 were higher in the female brain than in the male brain. Equally importantly, no conspicuous sex differences were observed in the expression of gnrh2, th1, and th2, despite several previous reports of their sex-biased expression in the brains of other teleost species. Taken together, these data have uncovered previously unidentified sex differences in the expression of VT/IT, GnRH, and TPH in the teleost brain, which may possibly be relevant to sexual dimorphism in some behavioral and/or physiological traits, and have simultaneously highlighted potential species differences in the roles of these molecules.

Studies have shown a few cerebral metabolites modified by cocaine in brain regions; however, endogenous metabolic profiling has been lacking. Ex vivo (1)H NMR spectroscopy-based metabonomic approach coupled with partial least squares was applied to investigate the changes of cerebral metabolites in nucleus accumbens (NAc) and striatum of rats subjected to cocaine treatment. Our results showed that both single and repeated cocaine treatment can induce significant changes in a couple of cerebral metabolites. The increase of neurotransmitters glutamate and gamma-amino butyric acid (GABA) were observed in NAc and striatum from the rats repeatedly treated with cocaine. Creatine and taurine increased in NAc whereas taurine increased and creatine decreased in striatum after repeated cocaine treatment. Elevation of N-acetylaspartate in NAc and striatum and decrease of lactate in striatum were observed, which may reflect the mitochondria dysregulation caused by cocaine; moreover, alterations of choline, phosphocholine and glycerol in NAc and striatum could be related to membrane disruption. Moreover, groups of rats with and without CPP apparatus are presenting difference in metabolites. Collectively, our results provide the first evidence of metabonomic profiling of NAc and striatum in response to cocaine, exhibiting a regionally-specific alteration patterns. We find that repeated cocaine administration leads to significant metabolites alterations, which are involved in neurotransmitters disturbance, oxidative stress, mitochondria dysregulation and membrane disruption in brain.

Brain edema is an important complication of acute hepatic encephalopathy (AHE), and astrocyte swelling is largely responsible for its development. Elevated blood and brain ammonia levels have been considered as major etiological factors in this edema. In addition to ammonia, recent studies have suggested that systemic infection, inflammation (and associated cytokines), as well as endotoxin (lipopolysaccharide, LPS) are also involved in AHE-associated brain edema. As endothelial cells (ECs) are the first resident brain cells exposed to blood-borne "noxious agents"(i.e., ammonia, cytokines, LPS) that are present in AHE, these cells may be in a critical position to react to these agents and trigger a process resulting in astrocyte swelling/brain edema. We therefore examined the effect of conditioned media (CM) from ammonia, LPS and cytokine-treated cultured brain ECs on cell swelling in cultured astrocytes. CM from ammonia-treated ECs when added to astrocytes caused significant cell swelling, and such swelling was potentiated when astrocytes were exposed to CM from ECs-treated with a combination of ammonia, LPS and CKs. We also found an additive effect when astrocytes were exposed to ammonia along with CM from ammonia-treated ECs. Additionally, ECs treated with ammonia showed a significant increase in the production of oxy-radicals, nitric oxide, as well as evidence of oxidative/nitrative stress and activation of the transcription factor NF-κB. CM derived from ECs treated with ammonia, along with antioxidants or the NF-κB inhibitor BAY 11-7082, when added to astrocytes resulted in a significant reduction in cell swelling, as compared to the effect of CM from ECs-treated only with ammonia. We also identified increased nuclear NF-κB expression in rat brain cortical ECs in the thioacetamide model of AHE. These studies suggest that endothelial cells significantly contribute to the astrocyte swelling/brain edema in AHE, likely as a consequence of oxidative/nitrative stress and activation of NF-κB.

The temporal lobe plays a major role in anxiety and depression disorders and is also of importance for trait anxiety in the non-pathological range. The present study investigates self-report data of personality dimensions linked to trait anxiety in the context of white matter tract integrity in the temporal lobes of the human brain in a large sample of N = 110 healthy participants. The results show that especially in men values for fractional anisotropy of several white matter tracts in the temporal lobe of the left hemisphere correlate substantially with individual differences in trait anxiety (depending on the tract investigated between .40 and .49). The present study shows that not only data from functional magnetic resonance imaging (fMRI), but also structural diffusion tensor imaging (DTI) provides interesting insights into the biological foundation of human personality traits.

Synaptotagmin (syt) I is a Ca(2+) sensor that has been thought to trigger all vesicle secretion with similar mechanisms. However, given the calcium and stimulation requirements of small clear, and large dense core vesicles, we hypothesized that syt I expression differentially regulates vesicle release. Therefore, in this study, we generated multiple stable cell lines of PC12 cells that each had a different and stable level of syt I expression. We determined the functional effects of titrated syt I expression on transmitter release from the two vesicle types, and show that the transmitters, NE and NPY, each have a threshold level of syt I expression required for their release that is different for the two transmitter types.We used carbon fiber amperometry to measure release of NE from single vesicles, and found that release ranged from 50-100% in the syt I targeted cells compared to release from control cells.We used an immunoassay to measure NPY release and found that NPY release was abolished in cells that had abolished syt I expression, but cell lines that expressed 50-60% of control levels of syt I exhibited NPY release levels comparable to release of NPY from controls cells.Furthermore, the vesicle fusion pore exhibited a reduced open duration when syt I was abolished, but a longer open duration time for 50% syt I expression than control cells.Therefore, vesicles have a threshold for syt I that is required to control opening of the fusion pore, expansion, and full fusion to release large dense core proteins, but not for full fusion of the small molecules like NE.

Deep brain stimulation (DBS) is an emerging treatment of epilepsy. Anterior nucleus of the thalamus (ANT) is considered to be an attractive target due to its close connection to the limbic structures and wide regions of neocortex. The present study aimed to investigate the effects of high frequency stimulation (HFS) targeting the ANT on amygdala-kindled seizures in Wistar rats in two different stimulation modes i.e. pre-treatment and post-treatment stimulation, mimicking the scheduled and responsive stimulation in clinic use respectively. When fully-kindled seizures were achieved by daily amygdala kindling (1 s train of 1 ms pulses at 60 Hz), HFS (15 min train of 100 μs pulses at 150 Hz and 450-800 μA) was applied in two modes for 10 days. Bilateral post-treatment with HFS reduced the incidence of generalized seizures and the mean behavioral seizure stage and shortened average afterdischarge duration (ADD) and generalized seizure duration (GSD), while bilateral pre-treatment with HFS resulted in a similar but much weaker inhibition of seizures. On the other hand, we also found the two stimulation modes all increased the afterdischarge threshold and the differences of current intensity between afterdischarge threshold and generalized seizure threshold i.e. △(GST-ADT). However, △ (GST-ADT) increased by at least 20 μA in bilateral post-treatment group, while less in bilateral pre-treatment group. Additionally, unilateral post-treatment with HFS failed to inhibit seizures. Our data shown that anti-epileptic effect of bilateral post-treatment with HFS of ANT is much stronger than that of bilateral pre-treatment HFS, indicating bilateral responsive stimulation might be more appropriate for clinical anti-epileptic treatment of ANT HFS.

More than 125 years ago, Santiago Ramón y Cajal was able to draft and prove the neuron doctrine, and later, to develop prophetic theories about neural function and plasticity, many of which have been proven by current neuroscience. It was chance that made Cajal, during his doctorate studies, have his first contact with histology and force him to study the then current theories about pathogenesis of inflammation. Thus, he gained knowledge of the vascular hypothesis, by Julius Cohnheim, a German pathologist who, opposing the opinion of his teacher and father of cellular pathology, Rudolf Virchow, made leukocytes the protagonists of inflammation, given their ability to develop amoeboid movements directed by chemical signals. Cohnheim's chemotactic theory deeply influenced Cajal's conception of biology. So, the basic postulates of chemotaxis can be identified at different moments in Cajal's research, from the description of the "growth cone" in embryonic neuroblasts, the origin of the neurotrophic theory, to the proposal of the pathophysiological mechanisms of neuronal plasticity. From Cajal's point of view, the neurons move during its development and also to adapt to different external circumstances. Chemical endogenous substances can stimulate this movement in a similar way to leukocytes during the process of inflammation.

The olfactory bulb of mammals contains the major endogenous dopamine-producing system in the forebrain. The vast majority of dopaminergic neurons consists of juxtaglomerular cells, which innervate the olfactory glomeruli and modulate the entrance of sensory information to the olfactory bulb. Although dopaminergic juxtaglomerular cells have been widely investigated, the presence of dopaminergic interneurons other than juxtaglomerular cells has been largely unexplored. In this study, we analyze a population of tyrosine hydroxylase (TH)-containing interneurons located in the external plexiform layer of the rat olfactory bulb. These interneurons are GABAergic and morphologically heterogeneous. They have an axon and two to four dendrites running throughout the external plexiform layer. Frequently, they have appendages similar to spines in the dendrites and, sometimes, the distal portions of the dendritic branches show enlargements or swellings similar to varicosities. Contrary to other interneurons of the external plexiform layer, the TH-containing ones do not form dendro-dendritic synapses on principal cells and do not receive dendro-dendritic synapses from them. In fact, no synapses were found from the dendrites of these interneurons. When their dendrites are involved in synaptic contacts, they are always the postsynaptic element. They receive symmetrical and asymmetrical synapses from GABAergic and non-GABAergic axons of unidentified origin. Our data indicate that the local circuits of the external plexiform layer are more complex than previously thought. Although most of the interneurons of this layer establish dendro-dendritic synaptic relationships with principal cells, the TH-containing interneurons constitute an exception to this rule, resembling interneurons from other cortical areas.

Sympathetic preganglionic neurons (SPNs) in the intermediolateral (IML) and dorsal commissural nucleus (DCN) of the thoracolumbar segments of the spinal cord contribute to the autonomic control of the pelvic visceral organs. We examined the morphology of these neurons at the light and electron microscopic level and quantified the boutons apposing the soma and proximal dendrites of the SPNs innervating the major pelvic ganglion in female rats. The majority of these cells resided in the DCN (61.6 ± 6.2%) and IML (33.2 ± 4.4%) nuclei. Measurements of cell volume and shape revealed no differences between SPNs sampled from the DCN and IML populations. Ultrastructural studies of DCN and IML SPNs revealed that coverage of SPNs by synaptic inputs is sparse, with an average of 11.60 ± 2.41% of the soma membrane and 16.33 ± 6.18% of proximal dendrites apposed by boutons, though some somata exhibited no synaptic coverage. Three distinct types of boutons were found to appose the SPN somata and dendrites. The putatively inhibitory F-type bouton covered a significantly greater percentage of membrane on the soma (8.48 ± 2.12%) and dendrites (12.65 ± 4.34%), than the S-type bouton, a putatively excitatory bouton, which only covered 2.94 ± 0.70% of the somatic and 3.68 ± 2.98% of the dendritic membranes. Boutons with dense-core vesicles were rare. Our results demonstrate that SPNs of the DCN and IML of female rats are similar morphologically, and that synaptic input on these cells, though sparse, is predominantly inhibitory.

Reactive gliosis has been implicated in injury and recovery patterns associated with hydrocephalus. The roles that these mechanisms play in the pathophysiology of hydrocephalus are still not clear in terms of cytopathology and gene expression. In this paper, we investigated the relationship between reactive gliosis and neuroinflammation of hydrocephalic rats of different severity at both cellular and molecular levels. Therefore thirty five adult SD rats were randomly divided into the normal group(n=5), the sham operation group(n=5) and the model group (n=25). Hydrocephalic rat models were induced by intraventricular injections of 3% kaolin, and the ventricular dilatation were examinated by MRI at 2-week postoperation. Then the model group were subdivided into the mild group(n=5), the moderate group(n=7) and the severe group (n=9) according to the degree of ventricular dilatation. While IL-18, GFAP, Iba-1 were detected by ELISA, RT-PCR, Immunohistochemistry and western blot and correlation analysis was conducted at the same time. According to the result comparison between the normal group and the sham operation group, the ventricle of model group were obviously enlarged (P < 0. 01). The expression of GFAP and Iba-1 were increased (P < 0. 05) in brain tissue of model group and IL-18 was also increased in CSF sample of model group. It was revealed by correlation analysis that the increase was positively correlated with the severity of ventricular dilatation. Conclusion: These results indicate that gliosis and inflammation continue to rise dramatically in experimental hydrocephalus and can be regarded as the main factors of hydrocephalus. Regulating the level of gliosis and alleviateing inflammation may provide new therapeutic methods of hydrocephalus.

Histamine acts centrally to increase energy expenditure and reduce body weight by mechanisms not fully understood. It has been suggested that in the obese state hypothalamic histamine signaling is altered. Previous studies have also shown that histamine acting in the preoptic area controls thermoregulation. We aimed to study the influence of preoptic histamine on body temperature and energy homeostasis in control and obese mice. Activating histamine receptors in the preoptic area by increasing the concentration of endogenous histamine or by local injection of specific agonists induced an elevation of core body temperature and decreased respiratory exchange ratio (RER). In addition, the food intake was significantly decreased. The hyperthermic effect was associated with a rapid increase in mRNA expression of uncoupling proteins in thermogenic tissues, the most pronounced being that of uncoupling protein (UCP) 1 in brown adipose tissue and of UCP2 in white adipose tissue. In diet induced obese mice histamine had much diminished hyperthermic effects as well as reduced effect on RER. Similarly, the ability of preoptic histamine signaling to increase the expression of uncoupling proteins was abolished. We also found that the expression of mRNA encoding the H1 receptor subtype in the preoptic area was significantly lower in obese animals. These results indicate that histamine signaling in the preoptic area modulates energy homeostasis by regulating body temperature, metabolic parameters and food intake and that the obese state is associated with a decrease in neurotransmitter's influence.