DigitalUM :: Browsing by Subject "Hippocampus"

Browsing by Subject "Hippocampus"

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Age-related brain pathology in Octodon degu: blood vessel, white matter and Alzheimer-like pathology
(Elsevier, 2009-11-11) Van Groen, Thomas; Kadish, Inga; Popovic, Natalija; Popovic, Miroljub; Caballero Bleda, María; Baño-Otalora, Beatriz; Vivanco, Pablo; Rol, María Ángeles; Madrid, Juan Antonio; Anatomía Humana y Psicobiología
Recently it has been shown that over 3-year-old wild-type South American rodents, Octodon degus, the "common degu" or degu, of their own accord develop Alzheimer's disease neuropathological hallmarks: amyloid-β-peptide depositions and accumulation of tau-protein. Here we analyzed brains of 1-, 3- and 6-year-old degu's, bred in standard animal facilities. Significant amounts of Aβ and tau deposits are present in the hippocampal formation of 6-year-old O. degus, primarily in the white matter, but these hippocampal Aβ and tau deposits are not present in younger ones. In contrast, significant Aβ deposits in blood vessel walls are already found in 3-year-old animals. The tau deposits in the hippocampal formation coincide with a significant decrease in staining for myelin in the same areas, indicating hippocampal disconnection and, likely, dysfunction. Our findings indicate that (1) cerebral amyloid angiopathy precedes brain parenchyma pathology in aged degu's and (2) the onset of disease seems to be delayed in the laboratory vs. wild-type degu's.
Embargo
Circadian system functionality, hippocampal oxidative stress, and spatial memory in the APPswe/PS1dE9 transgenic model of Alzheimer disease: effects of melatonin or ramelteon
(Taylor and Francis Group, Taylor and Francis, 2012-07-23) Baño-Otalora, Beatriz; Popovic, Natalija; Gambini, Juan; Popovic, Miroljub; Viña, José; Bonet-Costa, Vicent; Reiter, Russel J.; Camello, Pedro Javier; Rol, María Ángeles; Madrid, Juan Antonio; Anatomía Humana y Psicobiología
Alzheimer disease (AD) is a neurodegenerative disorder that primarily causes β-amyloid accumulation in the brain, resulting in cognitive and behavioral deficits. AD patients, however, also suffer from severe circadian rhythm disruptions, and the underlying causes are still not fully known. Patients with AD show reduced systemic melatonin levels. This may contribute to their symptoms, since melatonin is an effective chronobiotic and antioxidant with neuroprotective properties. Here, the authors critically assessed the effects of long-term melatonin treatment on circadian system function, hippocampal oxidative stress, and spatial memory performance in the APPswe/PS1 double transgenic (Tg) mouse model of AD. To test if melatonin MT1/MT2 receptor activation, alone, was involved, the authors chronically treated some mice with the selective MT1/MT2 receptor agonist ramelteon. The results indicate that many of the circadian and behavioral parameters measured, including oxidative stress markers, were not significantly affected in these AD mice. During the day, though, Tg controls (Tg-CON) showed significantly higher mean activity and body temperature (BT) than wild-type (WT) mice. Overall, BT rhythm amplitude was significantly lower in Tg than in WT mice. Although melatonin treatment had no effect, ramelteon significantly reduced the amplitude of the BT rhythm in Tg mice. Towards the end of the experiment, Tg mice treated with ramelteon (Tg-RAM) showed significantly higher circadian rhythm fragmentation than Tg-CON and reduced circadian BT rhythm strength. The free-running period (τ) for the BT and locomotor activity (LA) rhythms of Tg-CON was <24 h. Whereas melatonin maintained τ at 24 h for BT and LA in both genotypes, ramelteon treatment had no effect. In the behavioral tests, the number of approaches and time spent exploring novel objects were significantly higher in Tg-CON than WT controls. Brain tissue analysis revealed significant reduction in hippocampal protein oxidation in Tg-MEL and Tg-RAM compared with Tg-CON animals. These results suggest that not all aspects of the circadian system are affected in the APPswe/PS1 mice. Therefore, care should be taken when extending the results obtained in Tg mice to develop new therapies in humans. This study also revealed the complexity in the therapeutic actions of melatonin and ramelteon in this mouse model of AD.
Open Access
Effect of chronic alcoholism on the human hippocampus
(Murcia : F. Hernández, 1990) Bengochea, O.; Gonzalo, L. M.
The effect of chronic alcoholism on the human hippocampus was studied in 21 patients, divided in 4 groups: Group A under 45 years, group B 46-59 years, group C 60-69, and Group D over 70 years; and compared with age-matched control patients who died without neurological complications. The gyrus d~ntatus and the ammonic fields CA1 through CA4 were analyzed by counting the number of neurons and the size of the nuclear area. Both parameters were evaluated statistically. The most important findings were a high neuronal loss in alcoholics in the first age group. In addition, the hippocampal neurons failed to display a vicarious reaction, since the nuclei did not show any increase in size despite the intense neuronal loss. Our results point out an early neuronal loss in the hippocampus of alcoholic patients higher than agematched controls, as well as a lack of reaction to the neuronal insult .
Open Access
Environmental enrichment preserves hippocampal neurons in diabetes and stressed rats
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Pamidi, N.; Yap, C.G.; Nayak, S.
This study evaluated the effect of Environmental Enrichment (EE) on neuron morphology in the CA1, CA3 and dentate hilus (DH) regions of the hippocampus by quantitating the total dendritic arborizations. EE is a potential intervention for stress and diabetes. It is capable of mitigating diabetes and stress-induced cognitive and memory deficit. Diabetes and stress were induced in male Wistar rats (4-5 weeks). Diabetic and stressed rats were exposed to EE on Day 2 post STZ injection and subsequently once daily for 30 days. All animals were sacrificed on Day 30. The hippocampus was dissected and processed for Golgi staining to quantitate dendritic arborizations at the CA1, CA2 and DH regions. Diabetes (D) and Diabetes+stress (D+S) groups had significantly fewer apical and basal dendritic branching points (ADBP, BDBP) at CA1 (p<0.01), CA3 (p<0.001) and DH (p<0.001) relative to control group (NC). Diabetes and stressed rats exposed to EE: [D+EE and D+S+EE groups] exhibited significantly denser ADBP and BDBP at all regions relative to D (p<0.001) and (D+S+EE) (p<0.001) groups respectively. EE significantly preserved neuronal arborizations in hippocampus of diabetic and stressed rats, suggesting a potential entity of diabetes and stress management.
Open Access
Enzyme histochemistry: a useful tool for examining the spatial distribution of brain ectonucleotidases in (patho)physiological conditions
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Grković, Ivana; Mitrović, Nataša; Dragić, Milorad; Kontić, Marina Zarić
Adenosine 5'-triphosphate (ATP) and other nucleotides and nucleosides, such as adenosine, are versatile signaling molecules involved in many physiological processes and pathological conditions in the nervous system, especially those with an inflammatory component. They can be released from nerve cells, glial cells, and vascular cells into the extracellular space where they exert their function via ionotropic (P2X) or metabotropic (P2Y) receptors. Signaling via extracellular nucleotides and adenosine is regulated by cell-surface located enzymes ectonucleotidases that hydrolyze the nucleotide to the respective nucleoside. This review summarizes a histochemical approach for detection of ectonucleotidase activities in the cryo-sections of brain tissue. The enzyme histochemistry (EHC) might be used as suitable replacement for immunohistochemistry, since it gives information about both localization and activity, thus adding a functional component to a classical histological approach. With this technique, it is possible to visualize spatial distribution and cell-specific localization of ectonucleoside triphosphate diphosphohydrolases (NTPDases) and ecto-5'-nucleotidase (eN/CD73) activities during brain development, after different hormonal manipulations, during neurodegeneration, etc. EHC is also suitable for investigation of microglial morphology in different (patho)physiological conditions. Furthermore, the review describes how to quantify EHC results.
Open Access
Hippocampal expressions of metallothionein I/II and glycoprotein 96 in EAE-prone and EAE-resistant strains of rats
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Grubić Kezele, Tanja; Blagojević Zagorac, Gordana; Jakovac, Hrvoje; Domitrović, Robert; Radošević Stašić, Biserka
Inflammatory demyelinating diseases such as multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) are often followed by cognitive deficits associated with the neuronal injury, synaptic loss and altered neurogenesis within the hippocampus. Changes depend on the genetic and epigenetic factors that ensure the cellular and environmental homeostasis and regulate the interactions of immunocompetent, glial and neural cells. Owing to high impact of stress proteins on these processes, in this study we compared the protein content of interleukin-6, transforming growth factor-β1, metallothioneins I/II (MTs) and glycoprotein 96 (gp96) in the hippocampus of DA and AO rats that differ in the susceptibility to the induction of EAE, and tested the relationship of MTs and gp96 to granule neurons, glial cells and neural progenitors in different subfields of dentate gyrus. Rats were immunized with bovine brain homogenate emulsified in complete Freund’s adjuvant or only with CFA. The data showed that acute attack of EAE in DA rats was followed by accumulation of IL-6, TGF-β1 and MTs proteins, by increased expression of MTs in molecular and granular cell layer, by reduced expression of gp96/granular cell, by apoptosis and by microgliosis with appearance of Iba-1+ cells, co-expressing MT I/II and gp96. Furthermore, in subgranular zone (SGZ) of DA rats an augmented number of GFAP+ precursors, but decreased number of doublecortin (DCX)+ neuroblasts and immature NeuN+ neurons were found, implying that in DA rats the neurogenesis was delayed or reduced. Besides, in SGZ of both strains several DCX+ and NeuN+ cells co-expressing gp96 and MT I/II were found.
Open Access
Histopathological changes of the hippocampus neurons in brain injury
(Murcia : F. Hernández, 2009) Dong Ri Li; Takaki Ishikawa; Dong Zhao; Tomomi Michiue; Li Quan; Bao Li Zhu; Hitoshi Maeda
The glial fibrillary acidic protein (GFAP) is known as a peculiar marker of mature astrocytes of the central nervous system (CNS). However, we found distinct immunopositivity to a monoclonal anti-GFAP reagent in the hippocampus neurons in head injury fatalities. The present study investigated the neuronal and neuroglial GFAP-immunopositivity in the hippocampus in a series of head injury cases, which included acute and subacute/delayed deaths (n=17 and n=73, respectively), and acute cardiac death (n=13), delayed death due to multiple organ failure from nonhead injury (n=6), and pneumonia (n=9) cases were examined as controls. GFAP-immunopositivity in the neurons was frequently observed in CA4, CA3 and CA2 regions in cases of subacute/delayed head injury death that showed marked brain swelling accompanied by secondary brain stem hemorrhages, showing an inverse relationship to that in astrocytes. These findings suggest possible induction of GFAP or a related protein in hippocampus neurons depending on the severity of brain swelling following head injury.
Open Access
Histopathological, immunohistochemical, and stereological analysis of the effect of Ginkgo biloba (Egb761) on the hippocampus of rats exposed to long-term cellphone radiation
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Gevrek, Fikret
Cellular phones are major sources of electromagnetic radiation (EMR) that can penetrate the human body and pose serious health hazards. The increasingly widespread use of mobile communication systems has raised concerns about the effects of cellphone radiofrequency (RF) on the hippocampus because of its close proximity to radiation during cellphone use. The effects of cellphone EMR exposure on the hippocampus of rats and the possible counteractive effects of Ginkgo biloba (Egb761) were aimed to investigate. Rats were divided into three groups: Control, EMR, and EMR+Egb761. The EMR and EMR+Egb761 groups were exposed to cellphone EMR for one month. Egb761 was also administered to the EMR+Egb761 group. Specifically, we evaluated the effect of RF exposure on rat hippocampi at harmful EMR levels (0.96 W/kg specific absorption rate [SAR]) for one month and also investigated the possible impact of Egb761 using stereological, TUNEL-staining, and immunohistochemical methods. An increase in apoptotic proteins (Bax, Acas-3) and a decrease in anti-apoptotic protein (Bcl-2) immuno-reactivity along with a decrease in the total granule and pyramidal cell count were noted in the EMR group. A decrease in Bax and Acas-3 and an increase in Bcl-2 immunoreactivity were observed in rats treated with Egb761 in addition to a decrease in TUNEL-stained apoptotic cells and a higher total viable cell number. In conclusion, chronic cellphone EMR exposure may affect hippocampal cell viability, and Egb761 may be used to mitigate some of the deleterious effects.
Embargo
Long-term social isolation in the adulthood results in CA1 shrinkage and cognitive impairment
(Elsevier, 2013-07-15) Pereda-Pérez, Inmaculada; Popovic, Natalija; Baño-Otalora, Beatriz; Popovic, Miroljub; Madrid, Juan Antonio; Rol, María Ángeles; Venero, Cesar; Anatomía Humana y Psicobiología
Social isolation in adulthood is a psychosocial stressor that can result in endocrinological and behavioral alterations in different species. In rodents, controversial results have been obtained in fear conditioning after social isolation at adulthood, while neural substrates underlying these differences are largely unknown. Neural cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) are prominent modulators of synaptic plasticity underlying memory processes in many tasks, including fear conditioning. In this study, we used adult female Octodon degus to investigate the effects of long-term social isolation on contextual and cued fear conditioning, and the possible modulation of the synaptic levels of NCAM and PSA-NCAM in the hippocampus. After 6½ months of social isolation, adult female degus showed a normal auditory-cued fear memory, but a deficit in contextual fear memory, a hippocampal dependent task. Subsequently, we observed reduced hippocampal synaptic levels of PSA-NCAM in isolated compared to grouped-housed female degus. No significant differences were found between experimental groups in hippocampal levels of the three main isoforms of NCAM (NCAM180, NCAM140 and NCAM120). Interestingly, social isolation reduced the volume of the hippocampal CA1 subfield, without affecting the volume of the CA3 subregion or the total hippocampus. Moreover, attenuated body weight gain and reduced number of granulocytes were detected in isolated animals. Our findings indicate for the first time, that long-term social isolation of adult female animals induces a specific shrinkage of CA1 and a decrease in synaptic levels of PSA-NCAM in the hippocampus. These effects may be related to the deficit in contextual fear memory observed in isolated female degus.
Open Access
Microglial cells during the lesion-regeneration of the lizard medial cortex
(Murcia : F. Hernández, 1999) Nacher, J.; Ramírez, G.; Palop, J.J.; Artal Soriano, Pablo; Molowny, A.; López-García, Carlos
The lizard medial cortex (lizard fascia dentata) is capable of neural regeneration after being lesioned by the anti-metabolite 3-acetylpyridine (3AP). This study was aimed at detecting microglial behaviour during the medial cortex lesion-regeneration process using tomato lectin histochemistry to label microglia (both with light and electron microscopy) and proliferating cell nuclear antigen (PCNA) immunocytochemistry to label proliferating cells. As expected, 1-2 days post-injection lectin-labelled microglia cells could not be observed in the medial cortex plexiform layers, but later (7 days post-injection) abundant lectin-labelled microglia cells re-populated the regenerating medial cortex. Abundant PCNA-immunolabelled nuclei were detected both in the subjacent ependymal neuroepithelium (neuroblasts, maximum at 2 days postinjection) as well as in some parenchyma1 cells which were also lectin-labelled (microglia, maximum at 7-15 days post-injection). Re-invasive microglia were also detected in the vicinity of ventricular ependymal lining, blood vessels and meninges. The electron microscope demonstrated that these microglial cells participate in cell debris removal, especially of neural granular cell somata. Other cell types related to microglia (mast cells, peri-vascular cells and meningeal cells) were also present during the scavenging process. Significant numbers of microglial cells remained in close relationship with the ependymal proliferative areas, even in control non-lesioned animals. This is indirect evidence for the working hypothesis that microglia are not only implicated in cell debris removal, but also in the regulation of newly generated neuroblast incorporation onto the cortical areas. Whether they phagocytose immature neuroblasts or induce cell death in them or even prevent their migration onto the principal layer areas are likely possibilities that remain to be proven.
Open Access
Morphine-withdrawal aversive memories and their extinction modulate H4K5 acetylation and Brd4 activation in the rat hippocampus and basolateral amygdala
(2023-06) Franco García, Aurelio; Gómez Murcia, Victoria; Fernández Gómez, Francisco José; González Andreu, Raúl; Hidalgo Céspedes, Juana María; Milanes Maquilón, María Victoria; Núñez Parra, María Cristina; Farmacología
Chromatin modification is a crucial mechanism in several important phenomena in the brain, including drug addiction. Persistence of drug craving and risk of relapse could be attributed to drug-induced epigenetic mechanisms that seem to be candidates explaining long-lasting drug-induced behaviour and molecular alterations. Histone acetylation has been proposed to regulate drug-seeking behaviours and the extinction of rewarding memory of drug taking. In this work, we studied the epigenetic regulation during conditioned place aversion and after extinction of aversive memory of opiate withdrawal. Through immunofluorescence assays, we assessed some epigenetic marks (H4K5ac and p-Brd4) in crucial areas related to memory retrieval -basolateral amygdala (BLA) and hippocampus-. Additionally, to test the degree of transcriptional activation, we evaluated the immediate early genes (IEGs) response (Arc, Bdnf, Creb, Egr-1, Fos and Nfkb) and Smarcc1 (chromatin remodeler) through RT-qPCR in these nuclei. Our results showed increased p-Brd4 and H4K5ac levels during aversive memory retrieval, suggesting a more open chromatin state. However, transcriptional activation of these IEGs was not found, therefore suggesting that other secondary response may already be happening. Additionally, Smarcc1 levels were reduced due to morphine chronic administration in BLA and dentate gyrus. The activation markers returned to control levels after the retrieval of aversive memories, revealing a more repressed chromatin state. Taken together, our results show a major role of the tandem H4K5ac/p-Brd4 during the retrieval of aversive memories. These results might be useful to elucidate new molecular targets to improve and develop pharmacological treatments to address addiction and to avoid drug relapse.
Open Access
Radial glia and cell debris removal during lesion-regeneration of the lizard medial cortex
(Murcia : F. Hernández, 1999) Nacher, J.; Ramirez, C.; Palop, J.J.; Molowny, A.; Luis de la Iglesia, J.A.; López-García, Carlos
Intraperitoneal injection of the neurotoxin 3- acetylpyridine (3AP) induces a rapid degeneration of the medial cerebral cortex (lizard fascia dentata) granular layer and of its zinc enriched axonal projection (lizard mossv fibres). After 6-8 weeks ~ost-lesionth e cell debris have ieen rekoved and the grakular layer is repopulated by neurons generated in the subjacent ependyma. Both processes, neuron incorporation and debris removal, seem to be crucial for successful regeneration. Scavenging processes in the lesioned mammalian CNS are usually carried out by microglia andlor astrocytes. In the lizard cerebral cortex there are no free astrocytes and the only glial fibrillary acid (GFAP) immunoreactive cells are radial glia-ependymocytes, similar to those present during mammalian CNS development. Ependymocytes, in addition to their help in vertical migrations of just generated immature neurons, built the cortical glial scaffold, insulate the blood capillaries, form the outer glial limiting membrane, thus playing an essential role in the lizard cortical blood-brain barrier. In this study, by means of GFAP-immunocytochemistry and electron microscopy, we have shown that radial glial cells participate actively in the removal/phagocytosis of cellular debris generated in the lesion process: mainly degenerated synapses, but interestingly, also some neuronal somata. Cell debris taken up by ependymocyte lateral processes seem to be progressively transported to either distal (pial) or proximal (ventricular) poles of the cell, where they result in lipofuscin accumulations. The hypothetical subsequent exchange of debris from ependymoglia by microglia/macrophages and Kolmer cells is discussed.
Open Access
Ultrastructure of the rat hippocampus after isobaric respirative hyperoxia
(Murcia : F. Hernández, 1991) Manthos, A.; Tsolaki, M.; Kaidoglou, K.; Alvanou, A.; Hatjinikolaou, K.; Hatjiagorakis, A.; Giala, M.; Foroglou, Ch.
After exposing rats to an environment of isobaric h,v ~eroxia.th e ~iltrastructurala lterations of the L hippocampus were studied. No major alterations were found in the nerve cells. Of importante was the moderate osmiophilia and the spindle-like transformation of the mitochondria. Vacuolated synapses and neuraxons were found, containing amorphous material. Astrocytic perivascular end feet were found vacuolated in many places. Many endothelial cells of the capillaries presented high osmiophilia, which sonletimes prevented structural details. Quantitatively, the findings were proportionally related to the time of exposure in the pure oxygen atmosphere (24,48 and 65 hours)

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