In this study the quantitative changes of the SP (senile plaque) and NFT (neurofibrillary tangle) in the intrinsic hippocampal neural circuit were analyzed. All patients (86 case) were diagnosed clinically and confirmed pathologically as Alzheimer disease. The results were: 1) The NET and SP were most prominenetly observed in the C/A1 region, but they were not so many in the CA2 and CA3 regions. 2) There were quantitative correlation between the NFT and the SP except in the presubiculum and the dentate fascia. 3) There were no significant rank correlation between the perikaryonic NFT and the terminal SP in the dentate fascia and the CA3 area. 4) There were significant statistic difference of the quantity of the NFT and the SP between each neighboring areas in the intrinsic hippocampal neural circuit. I think there could be some influences of cholinergic fiber that they were from the medial septal nuclei and the nuclei of the diagonal band to the dentate fascia and the CA3 area.
Alzheimer Disease* ; Cholinergic Fibers ; Dentate Gyrus ; Humans ; Neural Pathways* ; Septal Nuclei

The microscopic and quantitative study reported here examined peroxidase-positive granules in the senescenceacceleration prone mouse (SAMP10) brain and the senescence-resistant mouse (SAMR1) brain. Three-month-old and 14-month-old SAMP10 and SAMR1 mice were used in this stusy. Coronal brain sections were made, and then incubated with medium containing 0.05% 3, 3'-diaminobenzidine and 0.003% H2O2 in 0.1 M PB to visualize endogenous peroxidase activity. Peroxidase-positive granules were rarely found in the three-month-old SAMR1, whereas a few positive granules were observed in the young SAMP10 brains. Forteen-month-old animals showed frequent labelling for endogenous peroxidase. This labelling was distributed exclusively in periventricular regions such as the periventricular and arcuate hypothalamic nuclei surrounding the third ventricle, and the periventricular portion of the caudate-putamen and lateral septal nuclei surrounding the lateral ventricle. Double labelling with GFAP antiserum indicated that most DAB-positive granules in these regions were located within astrocytes. Image analysis showed that significantly more peroxidase-positive granules occurred with advancing age in both the SAMP10 and SAMR1 brains. However, the amount of these inclusions was significantly greater in the young as well as the aged SAMP10 brain than in the age-matched SAMR1 controls. Electron microscopic examination of the aged SAMP10 brain showed localization of endogenous peroxidase in astrocytes. They appeared as accumulated granules or inclusion bodies with homogeneously high electron density, rather than as diffusely scattered small particles. In summary, DAB-stained granules indicating the presence of peroxidase activity accumulated with ageing in both SAMP10 and SAMR1 brains, mainly in astrocytes of the periventricular brain regions. Further, the accumulation was more accelerated from younger ages and more extensively in the SAMP10 brain. These results suggest that astroglial changes might occur from young period in the periventricular region of the SAMP10, which might be associated with the neurological senescence in the SAMP10.
Aging ; Animals ; Astrocytes ; Brain* ; Humans ; Inclusion Bodies ; Infant ; Lateral Ventricles ; Mice* ; Peroxidase ; Septal Nuclei ; Third Ventricle

OBJECTIVES: Disrupted integrities of the fornix and stria terminalis have been suggested in schizophrenia. However, very few studies have focused on the fornix and stria terminalis comparing first-episode schizophrenia (FESZ), chronic schizophrenia (CS), and healthy controls (HCs) with the application of diffusion-tensor imaging (DTI) technique. The objective of this study is to compare the connectivity of the fornix and stria terminalis among FESZ, CS, and HCs. METHODS: We included the 44 FESZ patients, 39 CS patients and 20 HCs in this study. Voxel-wise statistical analysis of the fractional anisotropy (FA) data was performed using Tract-Based Spatial Statistics to analyze the connectivity of fornix and stria terminalis. In addition, the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS) were used to evaluate clinical symptom severities. RESULTS: There were no significant differences between the FESZ, CS, and HCs in age, sex, education years. The SAPS and SANS scores of the schizophrenia groups showed no significant differences. FA values of the right fornix cres/stria terminalis in the CS group were significantly lower than those in FESZ and HCs. There were no significant differences of FA values of the right fornix cres/stria terminalis between the FESZ and the HCs. Pearson correlation analyses revealed that significant correlation between FA values of the right fornix cres/stria terminalies of the the FESZ group and positive, negative symptom scales, and FA values of the right fornix cres/stria terminalis of the CS group and negative symptom scales. CONCLUSIONS: This study shows that FA values of the fornix and stria terminalis in the CS were lower than in the FESZ and the HCs. These results suggest that the fornix and stria terminalis can play a role in pathophysiology of schizophrenia. Thus current study can broaden our understanding of the pathophysiology of schizophrenia.
Anisotropy ; Education ; Fornix, Brain ; Humans ; Schizophrenia ; Septal Nuclei ; Weights and Measures ; White Matter

The present study has been performed to investigate the neural axis of rat digastric muscle using viral tracer, pseudorabies virus. The upper nuclei to innervate digastric muscle were in accumbens nucleus, agran-ular insular cortex, central nucleus of amygaloid, lateral septal nucleus, frontal cortex, and subfornical organ etc, in telencephalon ; arcuate hypothalamic nucleus, lateral hypot-halamic area, medial preoptic nucleus, bed nucleus of stria terminalis, dorsomedial hypot-halamic nucleus, suprachiasmatic nucleus, paraventricular nucleus, and retrochiasmatic area etc, in diencephalon ; nucleus Darkschewitsch, interstitial nucleus of the medial logitudinal fasciculus, parabrachial nucleus, locus ceruleus, Kolliker-Fuse nucleus, trigeminal mesencephalic nucleus, red nucleus, substantia nigra, nucleus of posterior commissure, Edinger-Westphal nucleus, and dorsal raphe nucleus etc, in mesencephalon ; giganto-cellular reticular nucleus, raphe magnus nucleus, raphe pallidus nucleus, raphe obscuous nucleus, nucleus of solitary tracts, lateral reticular nucleus, parvocellular reticular nucleus, area postrema, facial nucleus, pontine reticular nucleus, pontine nucleus of trigeminal nerve and spinal nucleus of trigeminal nerve etc, in rhombencephalon. There are significant difference of numbers of PRV-Ba immunoreactive cells between right and left sides of brain in almost nuclei[P< 0.05]. But PRV-Ba immunoreactive cells were observed only ipsilaterally in accessory trigeminal motor nucleus, accessory facial nucleus and agranular insular cortex. Frontal cortex was the only area which were shown contralateral immunoreactivity. The results of this study provide anatomical support that both the cranial and caudal bellies are innervated by the same upper nuclei. The results also support the suggestion that the lower nuclei of digastric muscle, accessory trigeminal motor nucleus and accessory facial nucleus consist of somatotopic motor complex.
Animals ; Area Postrema ; Axis, Cervical Vertebra* ; Brain ; Diencephalon ; Herpesvirus 1, Suid ; Hypothalamic Area, Lateral ; Immunohistochemistry ; Locus Coeruleus ; Mesencephalon ; Paraventricular Hypothalamic Nucleus ; Raphe Nuclei ; Rats* ; Red Nucleus ; Rhombencephalon ; Septal Nuclei ; Subfornical Organ ; Substantia Nigra ; Suprachiasmatic Nucleus ; Telencephalon ; Trigeminal Nerve ; Trigeminal Nuclei

Nitric oxide(NO) is thought to play an important role in development and plasticity of brain. In this study, we aimed to examine the expression of neuronal NOS and NADPH-diaphorase (NADPH-d) activity in the developing rat brain. The results show that there is a great variation in the time of appearance of the earliest NOS containing cells depending on their location: At the 15th embryonic day weakly stained cells were present in caudate-putamen, and neurons in the sensory trigeminal nucleus and the solitary nucleus displayed an intense staining. The NOS neurons in orbital neocortex, bed nucleus of stria terminalis, paraventricular hypothalamic nucleus, lateral hypothalamic area and mammillary body appeared first at the 18th embryonic day. The supraoptic nucleus and superior and inferior colliculi also weakly labeled at the 18th embryonic day, At the loth embryonic day, positive cells appeared in horizontal limb of diagonal band, anterior olfactory nucleus and parafascicular thalamic nucleus. In the cerebellum, weak NOS staining was present in fibers and cells situated below Purkinje cert layer. The Purkinje cell layer displayed a weak, rather diffuse activity throughout the cerebellum at postnatal day 0. At the 4th postnatal day. the reaction product in the Purkinje cell layer became more distinct. At the 10th postnatal day, the inner part of molecular layer became populated by NOS positive basket cells, and the reaction products on the Purkinje cells began to disappear. The present results showed that NOS in the rat brain is expressed in different populations of neurons at different stages of development. This expression pattern of NOS suggests that NO may play a role in the developmental remodelling of the mammalian brain.
Animals ; Brain* ; Cerebellum ; Extremities ; Hypothalamic Area, Lateral ; Inferior Colliculi ; Intralaminar Thalamic Nuclei ; Mamillary Bodies ; Neocortex ; Neurons ; Nitric Oxide Synthase* ; Nitric Oxide* ; Orbit ; Paraventricular Hypothalamic Nucleus ; Plastics ; Purkinje Cells ; Rats* ; Septal Nuclei ; Solitary Nucleus ; Supraoptic Nucleus ; Trigeminal Nuclei

OBJECTIVE: The hallmark of anxiety disorders is excessive fear. Previous studies have suggested that selective neural projections from Basal nucleus of stria terminalis (BNST) to amygdala and vice-versa precisely control the fear learning process. However the exact mechanism how the BNST controls fear consolidation and its extinction is largely unknown. In the present study we observed the changes in the BNST sub-regions following fear conditioning and its extinction. METHODS: The change in the number of positive neurons was determined by immunohistochemistry for Acetyl H3 (Histone 3), Acetyl H4 (Histone 4), cAMP response element binding Protein (CBP) and c-fos in three sub-regions of the BNST namely the anterio-lateral BNST (STLP) and anterio-medial BNST (STMA), and lateral-ventral BNST (STLV) of rats subjected to auditory fear conditioning and extinction. RESULTS: We found significant increase in the number of CBP, acetyl H3 and acetyl H4 positive neurons in the STMA and STLV but not in the STLP after fear conditioning. However, following fear extinction the number of CBP, acetyl H3 and acetyl H4 positive neurons increased significantly in the STLP but not in the STMA and STLV. Similar changes were observed in the number of c-fos positive neurons after fear consolidation and extinction. CONCLUSION: The results from this study suggest that the differential histone acetylation in the different sub-regions of the BNST following fear learning and its extinction may be responsible for changes in the neuronal activation patterns resulting in either fear or less fear.
Acetylation* ; Amygdala ; Animals ; Anxiety Disorders ; Cyclic AMP Response Element-Binding Protein ; Histones* ; Immunohistochemistry ; Learning ; Neurons ; Rats ; Septal Nuclei*

Nociceptin/orphanin FQ (N/OFQ) and its receptor, nociceptin opioid peptide (NOP) receptor, are localized in brain areas implicated in depression including the amygdala, bed nucleus of the stria terminalis, habenula, and monoaminergic nuclei in the brain stem. N/OFQ inhibits neuronal excitability of monoaminergic neurons and monoamine release from their terminals by activation of G protein-coupled inwardly rectifying K⁺ channels and inhibition of voltage sensitive calcium channels, respectively. Therefore, NOP receptor antagonists have been proposed as a potential antidepressant. Indeed, mounting evidence shows that NOP receptor antagonists have antidepressant-like effects in various preclinical animal models of depression, and recent clinical studies again confirmed the idea that blockade of NOP receptor signaling could provide a novel strategy for the treatment of depression. In this review, we describe the pharmacological effects of N/OFQ in relation to depression and explore the possible mechanism of NOP receptor antagonists as potential antidepressants.
Amygdala ; Antidepressive Agents ; Brain ; Brain Stem ; Calcium Channels ; Depression ; Habenula ; Models, Animal ; Neurons ; Neuropeptides ; Opioid Peptides ; Receptors, Drug ; Septal Nuclei

It has been proposed that nitric oxide is involved in the pathogenesis of cerebral ischemia-reperfusion. Because superoxide production is also enhanced during reperfusion, the cytotoxic oxidant peroxynitrite could be formed, but it is not known if this occurs following global forebrain ischemia-reperfusion. We examined whether peroxynitrite generation is increased in the vulnerable regions after forebrain ischemia-reperfusion. Transient forebrain ischemia was produced in the conscious rat by four-vessel occlusion. Rats were subjected to 10 or 15 min of forebrain ischemia. Immunohistochemical method was used to detect 3-nitrotyrosine, a marker of peroxynitrite production. 3-Nitrotyrosine immunoreactivity was enhanced in the hippocampal CA1 area 3 days after reperfusion. Furthermore, in rats subjected to ischemia for 15 min, this change was also observed in the lateral striatal region and the lateral septal nucleus 2apprx3 days after reperfusion. The cresyl violet staining of adjacent sections showed that neuronal cell death was induced in parallel with the nitrotyrosine immunoreactivity in the hippocampal CA1 area and the lateral striatal region. Our findings suggest that oxygen free radical accumulation and consequent peroxynitrite production play a role in neuronal death caused by cerebral ischemia-reperfusion.
Animals ; Brain* ; Cell Death ; Ischemia* ; Neurons ; Nitric Oxide ; Oxygen ; Peroxynitrous Acid* ; Prosencephalon* ; Rats* ; Reperfusion ; Septal Nuclei ; Superoxides ; Viola

The expression of c-fos and c-jun in the brain of the rat after capsaicin treatment was investigated by in situ hybridization, dot blot hybridization and immunocytochemical methods. Adult male Sprague-Dawley rats[200g] were used for this study. The first set of rats received a single subcutaneous injection of capsaicin[50mg/Kg] dissolved in 10% Tween-80 and 10% ethanol in saline. The rats were decapitated 1, 3, 5, 10, 24, 72 hours and 1 week after capsaicin treatment. The control set of rats were treated with saline instead of capsaicin. In situ hybridization and dot blot hybridization were carried out. O1igonucleotide probe complimentary to c-fos mRNA sequences were used for this study and labeling of oligonucleotides was accomplished using the DNA tailing kit. The expression of c-fos mRNA on the nucleus of neurons in in situ hybridization was observed throughout the brain, and was especially abundant in the olfactory cortex, nucleus of diagonal band of Broca, habenular nuclei, periaqueductal gray, parabrachial nucleus, entopeduncular nucleus, ventral posterolateral nucleus of the thalamus and cerebellum. Compared to the control rats, c-fos mRNA were increased 24 hours after capsaicin injection and gradually decreased after 72 hours, returning to the normal control level 1 week after capsaicin injection. c-fos mRNA was detected only 1 week after capsaicin injection in the various areas of the brain. The fos protein-like immunoreactivity was initially somewhat decreased at 24 hours, but increased at 72 hours and reactions was maximally observed at 1 week after capsaicin treatment. But Jun protein immunoreactivity was not increased, on the contrary, it was even decreased both in numbers of reactive cells and immunoreactivity 1 week after capsaicin injection. From the above results, c-fos gene expression was pronounced in the nucleus concerned with pain, olfaction and taste such as VPL nucleus of the thalamus, olfactory cortex and parabrachial nucleus, in the limbic system concerned with stress and emotion such as nucleus of diagonal band of Broca, periaqueductal gray and habenular nucleus, in the structure concerned with somatic motor function such as entopeduncular nucleus and cerebellum. Also, the c-fos gene was activated by the capsaicin early in the course of effects, then the fos protein increased as a results of c-fos activation. On the other hand, c-jun did not respond to capsaicin treatment early in the course, but Jun protein decreased late in the course of capsaicin effects.
Adult ; Animals ; Brain* ; Capsaicin* ; Cerebellum ; DNA ; Entopeduncular Nucleus ; Ethanol ; Genes, fos ; Habenula ; Hand ; Humans ; In Situ Hybridization ; Injections, Subcutaneous ; Limbic System ; Male ; Neurons ; Olfactory Pathways ; Oligonucleotides ; Periaqueductal Gray ; Rats* ; Rats, Sprague-Dawley ; RNA, Messenger ; Septal Nuclei ; Smell ; Thalamus ; Ventral Thalamic Nuclei

The hippocampus is known as involved in learning and memory functions and the entorhinal cortex plays a crucial role as a gateway connecting the several areas and hippocampal formation. Entorhinal cortex lesions have been employed in numerous studies as the Alzheimer's disease model. The purpose of this study were to identify the CNS hip-pocampal and cholinergic pathway and to investigate the morphological changes of the hippocampal cholinergic inner-vations by using the Pseudorabies virus injection into the hippocampus after entorhinal cortex lesions. The pseudorabies virus and double labelled neurons (ChAT and PRV) were distributed at several different nuclei including agranular insular cortex, bed nucleus of stria terminalis, central amygdala, globus pallidus, lateral segment, lateral hypothalamic area, laterodorsal tegmental nucleus, medial septal nucleus, mesencephalic reticular nucleus, periaqueductal gray matter and substantia innominata The morphological changes were observed in the hippocampal cholinergic innervation after entorhinal cortex lesions. These data suggested that the hippocampal cholinergic innervation showed morphological changes throughout the whole brain areas after entorhinal cortex lesion.
Alzheimer Disease ; Amygdala ; Animals ; Brain ; Entorhinal Cortex* ; Globus Pallidus ; Herpesvirus 1, Suid ; Hippocampus* ; Hypothalamic Area, Lateral ; Learning ; Memory ; Neurons ; Periaqueductal Gray ; Rats* ; Septal Nuclei ; Substantia Innominata