Hippocampal Cornu Ammonis Research Articles

Neuroprotective Effect of Celastrus Paniculatus Seed Extract on Epilepsy and Epilepsy-associated Cognitive Deficits.

Cognitive deficit is one of the common comorbidity accompanying epilepsy. The present study evaluated the effect of Celastrus paniculatus seed extract on seizure severity and cognitive deficit following the pentylenetetrazole (PTZ)-induced chemical kindling model. PTZ kindling model was developed by daily administration of the sub-convulsive dose of PTZ 30 mg/kg for four weeks. After four weeks of induction, the following treatment, namely sodium valproic acid (SVA) 200 mg/kg, C. paniculatus 500 mg\kg, pergolide 2 mg/kg, C. paniculatus (250 mg\kg)+ Pergolide (1 mg/kg), and C. paniculatus (250 mg\kg)+ SVA (100 mg/kg) were administered 30 minutes prior to PTZ (30 mg/kg) injection for a period of next 14 days. Neurobehavioral parameters, including superoxide dismutase (SOD), Catalase (CAT), glutathione (GSH), and dopamine levels were assessed and the Morris water maze test (MWM) and Grip strength test (GPS) were performed. Hematoxylin & Eosin (H&E) staining of hippocampal cornu ammonis (CA1), CA2, CA3, dentate gyrus (DG), and frontal cortex was performed. C. paniculatus (500 mg/kg) alone and in combination (C. paniculatus (250 mg\ kg)+ pergolide (1 mg/kg) and C. paniculatus (250 mg\kg)+ SVA (100 mg/kg)) significantly (P<0.05) reduced the seizure score, mean latency time, and distance traveled in the MWM. However, no significant effect was seen in GPS. Biochemical analysis showed elevated antioxidant markers, namely GSH, CAT, and SOD, and also elevated dopamine levels. C. paniculatus and its combination also significantly (P<0.05) protected against neuronal loss in the hippocampus and frontal cortex evidenced by H&E staining. C. paniculatus alone and in combination with other agents may have the potential to treat epilepsy and associated cognitive deficits.

Effects of the acute administration of delta-opioid receptor ligands on the excitability of rat hippocampal glutamate and brainstem monoamine neurons in vivo.

It was previously reported that the delta opioid receptor (DOR) agonist SNC80 and antagonist naltrindole modulate the excitability of hippocampal glutamate neurons in primary cultures. The present study aimed to investigate the acute effects of these ligands on the firing activity of hippocampal cornu ammonis 1/3 (CA1/3) glutamate, dorsal raphe nucleus (DRN) serotonin (5-HT), locus coeruleus (LC) noradrenaline, and ventral tegmental area (VTA) dopamine neurons in in vivo conditions. Adult Wistar male rats were used. SNC80 and naltrindole were administered intravenously. Neuronal firing activity was assessed using extracellular single-unit electrophysiology. SNC80, administered first at 1-3 mg/kg, dose-dependently inhibited CA1/3 glutamate, DRN 5-HT, and VTA dopamine neurons. Naltrindole, administered at 1-3 mg/kg after SNC80, did not have any additional effect. Naltrindole, administered first at 1-3 mg/kg, stimulated DRN 5-HT neurons in a dose-dependent manner; this stimulation was dose-dependently reversed by 1-3 mg/kg of SNC80. SNC80 and naltrindole inhibited LC noradrenaline neurons when only they were co-administered at 3 mg/kg, and only when SNC80 was administered first. In conclusion, DOR ligands alter the firing activity of hippocampal glutamate and brainstem monoamine neurons in in vivo conditions. The psychoactive effects of DOR ligands, reported in previous studies, might be explained, at least in part, by their ability to modulate the firing activity of hippocampal glutamate and brainstem monoamine neurons.

Activation of CREB-BDNF Pathway in Pyramidal Neurons in the Hippocampus Improves the Neurological Outcome of Mice with Ischemic Stroke.

Cerebral ischemia is characterized by several pathological reaction evolving over time. Hyperactivation of glutamatergic neurons is the main factor leading to excitotoxicity which potentiates oxidative stress and triggers the mechanisms of neural apoptosis after cerebral ischemia. However, it is unclear whether glutamate in the ventral hippocampal Cornus Ammonis 1 (vCA1) acts a part in neurological deficits, pain perception, anxiety, and depression induced by ischemic stroke. We investigated the effects of chemogenetic inhibition or activation of vCA1 pyramidal neurons which are mainly glutamatergic neurons on sequelae induced by cerebral ischemia. Our results revealed that inhibition of vCA1 pyramidal neurons by chemogenetics alleviated neurological deficits, pain perception, anxiety, and depression caused by cerebral ischemia in mice, but activation of vCA1 pyramidal neurons had limited effects. Moreover, we found that stroke was accompanied by decreased levels of cAMP-response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in vCA1, which are modulated by glutamate. In this study, overexpression of CREB protein in pyramidal neurons in vCA1 by AAV virus significantly upregulated the content of BDNF and ameliorated the dysfunction induced by ischemic stroke. Our results demonstrated activation of the CREB-BDNF pathway in vCA1 pyramidal neurons significantly improved neurological deficits, pain perception, anxiety, and depression induced by ischemic stroke.

Ranolazine Attenuates Brain Inflammation in a Rat Model of Type 2 Diabetes.

Recent studies suggest a pathogenetic association between metabolic disturbances, including type 2 diabetes (T2DM), and cognitive decline and indicate that T2DM may represent a risk factor for Alzheimer's disease (AD). There are a number of experimental studies presenting evidence that ranolazine, an antianginal drug, acts as a neuroprotective drug. The aim of the present study was to evaluate the effects of ranolazine on hippocampal neurodegeneration and astrocytes activation in a T2DM rat model. Diabetes was induced by a high fat diet (HFD) and streptozotocin (STZ) injection. Animals were divided into the following groups: HFD/STZ + Ranolazine, HFD/STZ + Metformin, HFD/STZ + Vehicle, NCD + Vehicle, NCD + Ranolazine and NCD + Metformin. The presence of neurodegeneration was evaluated in the hippocampal cornus ammonis 1 (CA1) region by cresyl violet staining histological methods, while astrocyte activation was assessed by western blot analysis. Staining with cresyl violet highlighted a decrease in neuronal density and cell volume in the hippocampal CA1 area in diabetic HFD/STZ + Vehicle rats, while ranolazine and metformin both improved T2DM-induced neuronal loss and neuronal damage. Moreover, there was an increased expression of GFAP in the HFD/STZ + Vehicle group compared to the treated diabetic groups. In conclusion, in the present study, we obtained additional evidence supporting the potential use of ranolazine to counteract T2DM-associated cognitive decline.

Inhibition of microRNA-200c preserves astrocyte sirtuin-1 and mitofusin-2, and protects against hippocampal neurodegeneration following global cerebral ischemia in mice.

Memory impairment remains a leading disability in survivors of global cerebral ischemia, occurring secondary to delayed neurodegeneration of hippocampal cornu ammonis-1 (CA1) neurons. MicroRNA-200c (miR-200c) is induced following ischemic stress and we have previously demonstrated that pre-treatment with anti-miR-200c is protective against embolic stroke in mice. In the present study we assessed the role of miR-200c on CA1 neurodegeneration, sirtuin-1 (SIRT1), and mitochondrial dynamic protein expression in a mouse model of transient global cerebral ischemia and in vitro in primary mouse astrocyte cultures after simulated ischemia. Mice were subjected to 10 min bilateral common carotid artery occlusion plus hypotension with 5% isoflurane. After 2 h recovery mice were treated with intravenous injection of either anti-miR-200c or mismatch control. Memory function was assessed by Barnes maze at post-injury days 3 and 7. Mice were sacrificed at post-injury day 7 for assessment of brain cell-type specific expression of miR-200c, SIRT1, and the mitochondrial fusion proteins mitofusin-2 (MFN2) and OPA1 via complexed fluorescent in situ hybridization and fluorescent immunohistochemistry. Global cerebral ischemia induced significant loss of CA1 neurons, impaired memory performance and decreased expression of CA1 SIRT1, MFN2, and OPA1. Post-injury treatment with anti-miR-200c significantly improved survival, prevented CA1 neuronal loss, improved post-injury performance in Barnes maze, and was associated with increased post-injury expression of CA1 SIRT1 and MFN2 in astrocytes. In vitro, primary mouse astrocyte cultures pre-treated with miR-200c inhibitor prior to oxygen/glucose deprivation preserved expression of SIRT1 and MFN2, and decreased reactive oxygen species generation, whereas pre-treatment with miR-200c mimic had opposite effects that could be reversed by co-treatment with SIRT1 activator. These results suggest that miR-200c regulates astrocyte mitochondrial homeostasis via targeting SIRT1, and that CA1 astrocyte mitochondria and SIRT1 represent potential post-injury therapeutic targets to preserve cognitive function in survivors of global cerebral ischemia.

Region-Specific Effects of Fractionated Low-Dose Versus Single-Dose Radiation on Hippocampal Neurogenesis and Neuroinflammation.

Despite technical advances in hippocampus-sparing radiotherapy, radiation-induced injury to neural stem cell compartments may affect neurocognitive functions. In pre-clinical mouse models with fractionated low-dose radiation (FLDR) and single-dose radiation (SDR), the accurate response to radiation-induced injury was analyzed in different hippocampal subregions. Adult and juvenile C57BL/6NCrl mice were exposed to FLDR (20 × 0.1 Gy, daily exposure from Monday to Friday for 4 weeks) or SDR (1 × 2 Gy). In addition, 72 h after the last exposure, neuroglia (astrocytes and microglia) and neuroprogenitor cells were characterized and quantified in the hippocampal cornu ammonis (CA) and dentate gyrus (DG) by immunofluorescence studies. After analyzing different hippocampal subregions, it was observed that radiation responses varied between non-neurogenic CA, with no detectable inflammatory alterations, and neurogenic DG, characterized by impaired neurogenesis and subsequent neuroinflammation. Age-dependent differences in radiosensitivity appeared to depend on the varying proliferative potential of neural stem cell niches. Using the same overall dose for FLDR and SDR (2 Gy), both the cumulative dose over time and also the single dose fraction have decisive impacts on hippocampal damage. Region-specific effects of radiation-induced hippocampal injury relies primarily on cell deaths of proliferating neuroprogenitors. Dose per fraction defines the extent of neuronal injury, and subsequently activated microglia and reactive astrocytes modulate dynamic processes of neuroinflammation. Thus, limiting both cumulative doses and dose fractions to hippocampal DG is an important issue of clinical radiotherapy to preserve neurocognitive functions.

Protective Effect of Metformin Alone or in Combination with Valproic acid on Pentylenetetrazole-Induced Seizures in Mice

Abstract Objective: The aim of this study was to investigate the effects of metformin on pentylenetetrazole (PTZ)-induced seizures and the neuroprotective effect of metformin on neuronal damage after pentylenetetrazole administration. Material and Methods: Thirty-five (35) Male BALB-c Albino mice weighing 35-38 g were divided randomly into five groups: Control group (1), Saline+PTZ group (2), Valproic Acid (VPA, 200 mg/kg intraperitoneal-i.p.)+PTZ group (3), Metformin (200 mg/kg i.p.)+PTZ group (4), and VPA+Metformin+PTZ group (5). The PTZ (60 mg/kg, i.p.) was injected 30 min after drugs injection to induce seizures and seizure stages and behavioral scoring were evaluated. After completing procedure, brain tissues were removed and analyzed with biochemical and histopathological procedures. The hippocampal Cornu Ammonis (CA) 1, CA2, CA3 and DG (dentate gyrus) regions were histopathologically evaluated and oxidative stress markers (total antioxidant status (TAS), total oxidant status (TOS)) were measured. Results: Compare to Saline+PTZ group, metformin administration alone did not affect the onset time of the first myoclonic jerk (FMJ), but combination of VPA and metformin significantly increased FMJ onset time (p&amp;lt;0.05). Additionally, the treatment of metformin with or without VPA reduced the brain oxidative stress (p&amp;lt;0.05). Furthermore, histopathological assessment demonstrated that metformin administration and the combination of VPA and metformin decreased dark neuron formation in the hippocampal CA1, CA2, CA3, and DG areas (p&amp;lt;0.05). Conclusion: Metformin was found to be significantly effective in reducing epileptic seizures, brain oxidative stress, and preventing neural damage after PTZ-induced seizure

Mastication stimuli enhance the learning ability of weaning-stage rats, altering the hippocampal neuron transcriptome and micromorphology.

Mastication stimuli are known to relieve senile dementia in human and animal studies. However, few studies have focused on its effect on weaning-stage animals and the underlying molecular processes. In this study, 3-week-old male rats were raised on a powdered (P-group) or chow (C-group) diet for 8 days, and their behavior was examined using the Y-maze and novel object recognition tests. In the Y-maze test, the C-group rats showed a larger alternation ratio than the P-group rats. In the novel object recognition test, the C-group rats exhibited a significantly larger discrimination index for novel objects than for familiar objects, but the P-group rats did not. We then compared the hippocampal neuron morphology and transcriptome between the groups. C-group rats exhibited larger dendrite branch numbers in the apical dendrites of pyramidal cells in the cornu ammonis 1 (CA1) region and a larger spine density in the basal dendrites of CA1 neurons than the P-group rats. Using DNA microarray analysis, we identified 621 (P < C) and 96 (P > C) genes that were differentially expressed between the groups. These genes were enriched in functional terms related to dendrite growth and included the Igf2, RhoA, and Rho GEF genes, most of which were upregulated in the C-group. These results suggest that the mastication stimuli during the weaning period can enhance the learning ability of rats by increasing the dendrite branches of hippocampal CA1 neurons and by regulating genes related to dendrite growth.

Effect of Sulpiride on Dopaminergic Synapse of Dorsal Hippocampus of Morphine-Treated Rats

Background: As previous studies show, several effects of morphine are induced by the dopaminergic system. Sulpiride is a dopamine D2 receptor (DAD2) antagonist widely used in clinics to treat DArelated disorders. DAD2 receptors are abundant at hippocampal cornu ammonis (CA1). Objectives: This study aimed to investigate the possible interaction of morphine and sulpiride on DA synapses in CA1. Materials &amp; Methods: In this study, 48 Wistar rats weighing 220 to 250 g were used. These animals were classified into eight groups (6 rats per group): saline control group (1 mL/kg), morphine group (5 mg/kg), sulpiride groups alone (1, 2, and 4 mg/kg) and sulpiride groups (1, 2, and 4 mg/ kg)+morphine (5 mg/kg). Saline or substances were injected once intraperitoneally. After 48 h, the animals’ brains were removed under anesthesia and placed in 10% formalin for fixation. Then, 3- to 4-μm slices were cut from these tissues, and the DA synapse was examined by histochemistry and immunohistochemistry techniques. The data were statistically analyzed by the analysis of variance. Results: The control group had DA synapses and healthy neurons. A relative increase in DA synapses compared to the control group was observed in the morphine and single sulpiride groups. However, in sulpiride+morphine groups, DA synapses were reduced compared to morphine or sulpiride alone, but neurons were not destroyed. Conclusion: The interaction effect of sulpiride and morphine in the CA1 region may decrease DA synapses.

Protective role of Vernonia Cinerea against the Carmoisine induced brain injury and anxiogenic effect in mice

ABSTRACT Carmoisine is a synthetic food additive which is commonly used in a wide range of food beverages. According to reports, excessive use of this coloring agent causes anxiogenic behavior in mice by inducing oxidative stress. The purpose of this study was to investigate the ameliorating effects of Vernonia Cinerea against carmoisine-induced brain injury and anxiogenic-like effects in mice. Results of behavioral studies revealed that Ethanol Extract of Vernonia Cinerea (EEVC) has anxiolytic activity. Furthermore, carmoisine administration resulted in a significant increase in neuro-chemicals such as glutamate and a depletion of Gamma-Amino Butyric Acid levels (p < 0.001) and antioxidant enzymes such as catalase, and superoxide dismutase levels (p < 0.05), confirming brain tissue damage, while EEVC administration (400 mg/kg p.o.) reversed these biochemical alterations significantly (p < 0.05) as compared to the normal control and carmoisine-treated groups. To a remarkable extent, the extract causes significant changes in neurochemicals. Furthermore, EEVC administration significantly increased the levels of various in vivo antioxidants. Furthermore, EEVC reversed hippocampus Cornu Ammonis 3 (CA3) area complications such as intense vocalization, cyanosis, and hemorrhage when compared to carmoisine groups. From the results, EEVC has shown significant anxiolytic and ameliorating potential against carmoisine-induced brain injury evidenced by a significant reversal of biochemical, neurochemical parameters along with significant improvement of antioxidant activities.

The modulatory role of dopamine receptors within the hippocampal cornu ammonis area 1 in stress-induced analgesia in an animal model of persistent inflammatory pain.

The intrinsic pain inhibitory mechanisms can be activated by fear, anxiety, and stress. Stressful experiences produce analgesia, referred to as stress-induced analgesia (SIA). Major components of the limbic system, including the ventral tegmental area, nucleus accumbens, amygdala, and hippocampus, are involved in the SIA. In this study, we tried to understand the role of dopamine receptors in the cornu ammonis area 1 (CA1) of the hippocampus in the forced swim stress (FSS)-induced analgesia. Stereotaxic surgery was unilaterally performed on 129 adult male Wistar rats weighing 220-280 g. SCH23390 (0.25, 1, and 4 μg/0.5 μl saline) or sulpiride (0.25, 1, and 4 μg/0.5 μl DMSO), as D1- and D2-like dopamine receptor antagonists, respectively, were microinjected into the CA1 area, 5 min before exposure to FSS for a 6-min period. The vehicle groups received saline or DMSO instead of SCH23390 or sulpiride, respectively. The formalin test was done using formalin injection (50 μl; 2.5%) into the plantar surface of the rat's hind paw immediately after exposure to FSS. The results demonstrated that FSS produces analgesia during the early and late phases of the formalin test. However, intra-CA1 microinjection of SCH23390 or sulpiride attenuated the FSS-induced analgesia in both phases of the formalin test. This study provides new insight into the role of D1- and D2-like dopamine receptors in the CA1 area in the FSS-induced analgesia during persistent inflammatory pain.

Apelin-13 attenuates depressive-like behaviors induced by chronic unpredictable mild stress via activating AMPK/PGC-1α/FNDC5/BDNF pathway

Chronic stress induces neuronal death and impairs hippocampal neurogenesis, thus leading to cognitive deficits and depressive-like behaviors. Our previous studies found that apelin-13, a novel neuropeptide, and its receptors can improve cognitive impairment and depressive-like behaviors in rats, but its mechanism remains unknown. The study aims to evaluate the underlying mechanism of apelin-13 on cognitive impairment and depressive-like behaviors. A 4-week chronic unpredictable mild stress (CUMS) is used to establish a rat model of depression. Apelin-13(2 ug/day) is administered daily to the rats during the last 1 week. Depressive-like behaviors, including tail suspension test (TST) and sucrose preference test (SPT), are performed. The cognitive functions are established by identify index of novel objects recognition test (NORT) and the number of crossing hidden platform in morris water maze (MWM). The neuronal death is measured by popidium iodide (PI) and flow cytometry. The activity of superoxide dismutase (SOD) and glutathione-peroxidase (GSH-PX) in the hippocampus are determined. The protein expressions of p-AMPK, AMPK, BDNF, FNDC5 and PGC-1α are examined. Golgi staining observed the spine dendritic arborization of the hippocampal cornu ammonis 1 (CA1) subregion. Results showed that apelin-13 improves cognitive impairment and ameliorates depressive-like behaviors. Moreover, apelin-13 significantly inhibits neuronal death via AMPK/PGC-1α/FNDC5/BDNF pathway. Taken together, apelin-13 could exert antidepressant effects via protecting neuron functions, which might be related to the activation of AMPK/PGC-1α/FNDC5/BDNF pathway.

Forgetting the Unforgettable: Transient Global Amnesia Part II: A Clinical Road Map.

Transient global amnesia (TGA) is a clinical syndrome characterized by the sudden onset of a temporary memory disorder with profound anterograde amnesia and a variable impairment of the past memory. Usually, the attacks are preceded by a precipitating event, last up to 24 h and are not associated with other neurological deficits. Diagnosis can be challenging because the identification of TGA requires the exclusion of some acute amnestic syndromes that occur in emergency situations and share structural or functional alterations of memory circuits. Magnetic Resonance Imaging (MRI) studies performed 24–96 h after symptom onset can help to confirm the diagnosis by identifying lesions in the CA1 field of the hippocampal cornu ammonis, but their practical utility in changing the management of patients is a matter of discussion. In this review, we aim to provide a practical approach to early recognition of this condition in daily practice, highlighting both the lights and the shadows of the diagnostic criteria. For this purpose, we summarize current knowledge about the clinical presentation, diagnostic pathways, differential diagnosis, and the expected long-term outcome of TGA.

Swimming exercise prevents hippocampal dendritic spine changes and memory loss caused by aging: An application of a new semi-automated spine analysis software

Dendritic spines are small, ratchet-like protrusions on neuronal dendrites that form synapses for receiving neuronal messages. Dendritic spine morphology is associated with synapse function. If neurons degrade or are damaged, the spine morphology of neurons changes. Given that most commercially available spine analysis software is expensive and complex, this study investigated a semi-automated spine analysis software, CTSpine, and used previously published data to verify the accuracy of the analysis results of this software. We also applied CTSpine to understand whether aging causes alterations in the hippocampal spine morphology and whether physical exercise can impede dendritic spine changes in 20 male Sprague Dawley rats. The spines of pyramidal cells in the hippocampal Cornu Ammonis 1 (CA1) region in the aging group were more enriched in filopodium type pattern than those in the control group, whereas the spines of the exercised aging group showed a similar pattern to that of the control. No significant changes were observed in neuronal dendritic spines in other hippocampal regions. However, long-term hippocampal memory was considerably decreased in the aging group, which was reversed to some extent in the exercised aging group. CTSpine, a self-developed semi-automatic spine analysis software, showed results similar to those noted in published data and can be effectively applied to the study of dendritic patterns, including neurodevelopment and disease.

Forgetting the Unforgettable: Transient Global Amnesia Part I: Pathophysiology and Etiology.

Transient global amnesia (TGA) is a clinical syndrome characterized by the sudden onset of a temporary memory disorder with a profound anterograde amnesia and a variable impairment of the past memory. Since the first description, dating back over 60 years, several cases have beenreported in the literature. Nevertheless, TGA remains one of the most mysterious diseases in clinical neurology. The debate regarding the etiology of this disease has focused mainly on three different mechanisms: vascular (due to venous flow changes or focal arterial ischemia), epileptic, and migraine related. However, to date there is no scientific proof of any of these mechanisms. Furthermore, the demonstration by diffusion-weighted MRI of lesions in the CA1 field of the hippocampus cornu ammonis led us to hypothesize that the selective vulnerability of CA1 neurons to metabolic stress could play a role in the pathophysiology of TGA. In this review, we summarize current knowledge on the anatomy, vascularization and function of the hippocampus. Furthermore, we discuss the emerging theories on the etiology and the pathophysiological cascade leading to an impairment of hippocampal function during the attacks.

Ginkgo Biloba Extract Reduces Cardiac and Brain Inflammation in Rats Fed a HFD and Exposed to Chronic Mental Stress through NF-κB Inhibition.

Background Cardiac and brain inflammation can lead to a host of deleterious health effects. Our formal experimental research showed that Ginkgo Biloba Extract (GBE) contributed to the reduction of inflammation in mice with myocardial infarction along with depression. This study is aimed at expanding on these findings via analysis of the cardiac and brain inflammation, which was prevented by GBE in rats suffering with a high-fat diet (HFD) combined with unpredictable chronic mild stress (UCMS). Methods Fifty male Wistar rats were randomly divided into 5 groups treated with normal diet, UCMS, HFD, HFD+UCMS, or HFD+UCMS+GBE respectively. Rats treated with HFD were fed a high-fat diet for 10 or 13 weeks. Rats treated with UCMS were exposed to 8 types of chronic physical and psychological stressors for 10 or 13 weeks. The HFD+UCMS+GBE group was given GBE via intragastric gavage for 8 consecutive weeks. Sucrose preference was established for the assessment of depressive behaviors. The heart function was evaluated by echocardiography. The rats were terminated at the end of the 10th or 13th week. The blood was used for detecting low-density lipoprotein cholesterol (LDL-c) and total cholesterol (TCHO) by the kit instructions; Helper T Lymphocytes (TH cells, CD3+CD4+) by flow cytometry; and Interleukin- (IL-) 1β, IL-37, IL-38, NT-proBNP, hs-cTNI, and Ischemia-modified albumin (IMA) by enzyme-linked immunosorbent assay (ELISA). The cardiac tissues were used for detecting IL-1β, nuclear factor kappa B (NF-κB), inhibitor molecule protein (IκB), and IL-1 receptor (IL-1R) by ELISA and P65, P-P65, IκB, and phosphorylated inhibitor molecule protein α (P-IκBα) for western blotting. Cortex tissues were used for detecting 8-iso-prostaglandinF2α (8-iso-PGF2α) by ELISA. Oil Red staining was carried out to evaluate the lipid deposits in the rats' aortic arteries. Sirius Red staining was performed to display collagen fibers in the arteries. Hematoxylin and Eosin (HE) staining was applied to reveal pathological changes to arteries and cardiac tissue. Immunohistochemical staining was employed to assess the distribution of inflammatory cytokine IL-1β in arteries and cardiac tissues. Transmission Electron Microscopy (TEM) was performed to observe the ultrastructure of hippocampal cornu ammonis (CA)1 (CA1) neurons. Results In the rats with HFD+UCMS+GBE, over 13 weeks, GBE exerted a protective role of both the heart and brain, by attenuating cardiac inflammation and brain oxidative stress. Levels of Helper T lymphocytes and serum anti-inflammatory cytokines involving IL-37 and IL-38 were all elevated, and the depressive behaviors of HFD+UCMS rats were attenuated by GBE. This protective role was accomplished via inhibition of the canonical NF-κB signaling pathway, through downregulation of the expressions of P-P65 and P-IκB-α in the heart, hippocampus, cortex, and hypothalamus. Conclusions This study suggests that GBE poses a protective role from the various pathologies associated with high-fat diets, unpredictable chronic mild stress, and depression, possibly via improving peripheral immunity and reducing cardiac and brain inflammation.

Altered hippocampus and amygdala subregion connectome hierarchy in major depressive disorder

The hippocampus and amygdala limbic structures are critical to the etiology of major depressive disorder (MDD). However, there are no high-resolution characterizations of the role of their subregions in the whole brain network (connectome). Connectomic examination of these subregions can uncover disorder-related patterns that are otherwise missed when treated as single structures. 38 MDD patients and 40 healthy controls (HC) underwent anatomical and diffusion imaging using 7-Tesla MRI. Whole-brain segmentation was performed along with hippocampus and amygdala subregion segmentation, each representing a node in the connectome. Graph theory analysis was applied to examine the importance of the limbic subregions within the brain network using centrality features measured by node strength (sum of weights of the node’s connections), Betweenness (number of shortest paths that traverse the node), and clustering coefficient (how connected the node’s neighbors are to one another and forming a cluster). Compared to HC, MDD patients showed decreased node strength of the right hippocampus cornu ammonis (CA) 3/4, indicating decreased connectivity to the rest of the brain, and decreased clustering coefficient of the right dentate gyrus, implying it is less embedded in a cluster. Additionally, within the MDD group, the greater the embedding of the right amygdala central nucleus (CeA) in a cluster, the greater the severity of depressive symptoms. The altered role of these limbic subregions in the whole-brain connectome is related to diagnosis and depression severity, contributing to our understanding of the limbic system involvement in MDD and may elucidate the underlying mechanisms of depression.

Serotonin facilitates late-associative plasticity via synaptic tagging/cross-tagging and capture at hippocampal CA2 synapses in male rats.

Synaptic plasticity in the hippocampal Cornu Ammonis (CA) subfield, CA2, is tightly regulated. However, CA2 receives projections from several extra-hippocampal modulatory nuclei that release modulators that could serve to fine-tune plasticity at CA2 synapses. Considering that there are afferent projections from the serotonergic median raphe to hippocampal CA2, we hypothesized that the neuromodulator serotonin (5-hydroxytryptamine; 5-HT) could modulate CA2 synaptic plasticity. Here, we show that bath-application of serotonin facilitates the persistence of long-term depression (LTD) at the CA3 Schaffer collateral inputs to CA2 neurons (SC-CA2) when coupled to a weak low frequency electrical stimulation, in acute rat hippocampal slices. The observed late-LTD at SC-CA2 synapses was protein synthesis- and N-methyl-D-aspartate receptor (NMDAR)-dependent. Moreover, this late-LTD at SC-CA2 synapses paves way for the associative persistence of transient forms of LTD as well as long-term potentiation to long-lasting late forms of plasticity through synaptic tagging and cross-tagging respectively, at the entorhinal cortical synapses of CA2. We further observe that the 5-HT-mediated persistence of activity-dependent LTD at SC-CA2 synapses is blocked in the presence of the brain-derived neurotrophic factor scavenger, TrkB/Fc.

Morphine Consumption During Lactation Impairs Short-Term Neuronal Plasticity in Rat Offspring CA1 Neurons

Background: Facing environmental factors during early postnatal life, directly or indirectly via mother-infant relationships, profoundly affects the structure and function of the mammals’ Central Nervous System (CNS). Objectives: This study aimed to evaluate the effect of morphine consumption during the lactation period on short-term synaptic plasticity of the hippocampal Cornu Ammonis 1 (CA1) neurons in rat offspring. Materials &amp; Methods: In addition to a group of control mother rats (CO), three groups subcutaneously received 5 (M5), 10 (M10), or 20 (M20) mg/kg morphine every 12 hours during the lactation period. At 45 days old, following the stimulation of the Schaffers’ collaterals, basic field Excitatory Post-Synaptic Potentials (fEPSPs) were recorded in their offspring’s hippocampal CA1 neuronal circuits. After the construction input/output curve, paired-pulse stimulations with the inter-stimulus intervals of 20, 80, and 200 ms were applied to determine the short-term synaptic plasticity, and the paired-pulse ratio was evaluated. Results: The baseline synaptic responses of the rats CA1 neurons whose mothers received 10 and 20 mg/kg morphine twice daily during the lactation period decreased compared to the CO animals (P&lt;0.01 &amp; P&lt;0.001, respectively). Furthermore, compared to the controls, the Paired-Pulse Ratio (PPR) of the CA1 neural circuits of M10 and M20 rats at 20 and 80 ms Inter-Stimulus Intervals (ISI) decreased (P&lt;0.01). Conclusion: Morphine exposure during the lactation period has a detrimental impact on the primary synaptic activity and short-term synaptic plasticity of the hippocampal CA1 neuronal circuits of rats’ offspring.

Astaxanthin Confers a Significant Attenuation of Hippocampal Neuronal Loss Induced by Severe Ischemia-Reperfusion Injury in Gerbils by Reducing Oxidative Stress.

Astaxanthin is a powerful biological antioxidant and is naturally generated in a great variety of living organisms. Some studies have demonstrated the neuroprotective effects of ATX against ischemic brain injury in experimental animals. However, it is still unknown whether astaxanthin displays neuroprotective effects against severe ischemic brain injury induced by longer (severe) transient ischemia in the forebrain. The purpose of this study was to evaluate the neuroprotective effects of astaxanthin and its antioxidant activity in the hippocampus of gerbils subjected to 15-min transient forebrain ischemia, which led to the massive loss (death) of pyramidal cells located in hippocampal cornu Ammonis 1-3 (CA1-3) subfields. Astaxanthin (100 mg/kg) was administered once daily for three days before the induction of transient ischemia. Treatment with astaxanthin significantly attenuated the ischemia-induced loss of pyramidal cells in CA1-3. In addition, treatment with astaxanthin significantly reduced ischemia-induced oxidative DNA damage and lipid peroxidation in CA1-3 pyramidal cells. Moreover, the expression of the antioxidant enzymes superoxide dismutase (SOD1 and SOD2) in CA1-3 pyramidal cells were gradually and significantly reduced after ischemia. However, in astaxanthin-treated gerbils, the expression of SOD1 and SOD2 was significantly high compared to in-vehicle-treated gerbils before and after ischemia induction. Collectively, these findings indicate that pretreatment with astaxanthin could attenuate severe ischemic brain injury induced by 15-min transient forebrain ischemia, which may be closely associated with the decrease in oxidative stress due to astaxanthin pretreatment.