Neurons In CA1 Area Research Articles

Influencing Factors of Prepulse Inhibition Deficit in Patients with Schizophrenia and Observations on the Efficacy of Traditional Chinese Medicine

This study aims to analyze the abnormal expression of lncRNAs in peripheral blood mononuclear cells (PBMCs) of patients with schizophrenia, investigate the influencing factors of prepulse inhibition deficit in patients and observe the efficacy of traditional Chinese medicine. A total of 106 patients with schizophrenia who underwent treatment at our hospital from January 2020 to December 2022 were included, along with 45 healthy individuals who received routine check-ups as control subjects. The significantly expressed lncRNAs were validated and analyzed using ROC curve analysis, and logistic regression analysis was used to identify the factors influencing prepulse inhibition deficit. Find 125 lncRNAs were found to be differentially expressed lncRNAs in the PBMCs of patients with schizophrenia, including 62 upregulated and 63 downregulated lncRNAs. And smoking amount, and relapse frequency were influencing factors for prepulse inhibition deficit in patients with schizophrenia. Animal experiments were conducted using hematoxylin eosin staining to observe the number and morphology of neurons in the hippocampal CA3 area and prefrontal cortex of rats, and the effects of natural Chinese medicine Poria cocos on the nervous system were analyzed. Find the acidic polysaccharides from Poria cocos, a natural traditional Chinese medicine, can promote the regeneration of neuronal cells, reduce excessive autophagy of neurons in the CA3 area of the hippocampus and prefrontal cortex of rats, promote neuronal cell proliferation, and improve neuronal cell morphology. Traditional Chinese medicine has good effects in psychopathology, positive and negative symptoms, and PANSS total score. Disruption of lncRNA expression may be one of the biological factors contributing to the pathogenesis of schizophrenia and is closely related to its mechanism. Prepulse inhibition, reflecting sensory gating function, is an important factor affecting perceptual and cognitive functions in patients with schizophrenia. Gender, smoking amount, and relapse frequency may influence prepulse inhibition deficit in these patients. Traditional Chinese medicine shows potential in improving prepulse inhibition deficit. The acidic polysaccharides from Poria cocos, a natural traditional Chinese medicine, can promote the regeneration of neuronal cells, effectively improve the damage to the structure and function of neurons in the hippocampal CA3 area and prefrontal cortex. When used in combination with other traditional Chinese medicines, it could offer new approaches for treating schizophrenia.

Neuroprotective and anti-neuroinflammatory activity of frankincense in bile duct ligaion-induced hepatic encephalopathy.

Hepatic encephalopathy induces cognitive disturbances. Patients show neuroinflammation due to accumulation of toxic substances. Frankincense has neuroprotective and anti-inflammatory properties. Accordingly, we intended to evaluate the impact of frankincense on memory performance, inflammation, and the amount of hippocampal neurons in bile duct-ligated rats. The bile duct was ligated in three groups of adult male Wistar rats (BDL groups). In two of these groups, frankincense was administered (100 or 200 mg/kg; by gavage) starting from one week before surgery to 28 days after surgery. The third BDL group received saline. In the sham group, the bile duct was not ligated and the animals received saline. Twenty-eight days after surgery, spatial memory was evaluated by the Morris water maze test. Five rats from each group were sacrificed to measure the expression of the hippocampal tumor necrosis factor-alpha (TNF-α). Three rats from each group were perfused to determine the amount of hippocampal neurons. Bile duct ligation impaired memory acquisition, while frankincense amended it. Bile duct ligation significantly increased the expression of TNF-α. Frankincense reduced TNF-α in BDL rats, significantly. The number of neurons in the hippocampal CA1 and CA3 areas was significantly lower in the BDL group and in the group that received frankincense (100 mg/kg) equated to the sham group. Frankincense (200 mg/kg) augmented the amount of neurons in the CA1 area, slightly and in the CA3 area, significantly. The results indicate the anti-inflammatory and neuroprotective effects of frankincense in bile duct ligation-induced hepatic encephalopathy.

Naringin prevents the reduction of the number of neurons and the volume of CA1 in a scopolamine-induced animal model of Alzheimer’s disease (AD): a stereological study

Despite several therapies, the effective treatment of Alzheimer's disease remains a global challenge. Hence, natural products might act as an alternative treatment for Alzheimer's disease. Naringin, a polyphenol, possesses promising potential in the treatment of neurodegenerative disorders. Therefore, we investigated the effect of naringin on scopolamine-induced inhibitory passive avoidance memory impairment, CA1 volume, and neuronal loss by using stereological methods. After the scopolamine intraperitoneal injection, rats were treated with naringin (50, 100, and 200 mg/kg/day) for 14 consecutive days via intraperitoneal injection. The inhibitory passive avoidance test was performed for the memory test. 24 hours after the behavioral test; rats’ brains were removed from the skull and fixed with 4% paraformaldehyde. The rats’ brains cut and sections coronal, were stained using the cresyl violet staining for neurons. Finally, the changes in the neurons of the hippocampal CA1 area were examined stereologically. We observed that naringin ameliorated significantly inhibitory passive avoidance memory. Scopolamine decreased significantly the volume of the hippocampal CA1 area and naringin injection with doses of 50, 100, and 200 mg/kg, increased the volume of the hippocampal CA1 area. Naringin administration at doses of 50, 100, and 200 mg/kg for 14 consecutive days, increased neuron density and the total number of neurons in the hippocampal CA1 area. We concluded that naringin could be effective in improving scopolamine-induced inhibitory passive avoidance memory deficits and that it appeared to increase the volume and density as well as the total number of neurons in the CA1 area of the Alzheimer's rat hippocampus.

Sarsasapogenin attenuates Alzheimer-like encephalopathy in diabetes

BackgroundA crosstalk exists between diabetes and Alzheimer's disease (AD), and diabetic encephalopathy displays AD-like disorders. Sarsasapogenin (Sar) has strong anti-inflammatory efficacy, showing neuroprotection and memory-enhancement effects. PurposeThis study aims to verify the ameliorative effects of Sar on diabetic encephalopathy in vivo and in vitro, and to clarify the mechanisms from attenuation of AD-like pathology. MethodsStreptozotocin-induced type 1 diabetic rats and high glucose-cultured SH-SY5Y cells were used in this study. After Sar treatment (20 and 60 mg/kg) for consecutive 9 weeks, Morris water maze and novel object recognition tasks were performed. Hematoxylin-eosin staining was used for examining loss of neurons in CA1 area and ki67 expression for reflecting neurogenesis in DG area of hippocampus. Aβ production pathway and tau phosphorylation kinase cascade were examined in these two models. ResultsSar improved learning and memory ability, loss of neurons and reduction of neurogenesis in the hippocampus of diabetic rats. Moreover, Sar suppressed Aβ overproduction due to up-regulation of BACE1 in protein and mRNA and tau hyperphosphorylation from inactivation of AKT/GSK-3β cascade in the hippocampus and cerebral cortex of diabetic rats and high glucose-cultured SH-SY5Y cells, and PPARγ antagonism abolished the effects of Sar on key molecules in the two pathways. Additionally, it was found that high glucose-stimulated Aβ overproduction was prior to tau hyperphosphorylation in neurons. ConclusionSar alleviated diabetic encephalopathy, which was obtained through inhibitions of Aβ overproduction and tau hyperphosphorylation mediated by the activation of PPARγ signaling. Hence, Sar is a good candidate compound for AD-like disorders.

Effect of DL-3-n-butylphthalide on cognitive function and the regulating role of Nrf2/SIRT3 signaling pathway in vascular dementia mice

Objective To investigate the effects of butylphthalide(NBP) on cognitive function and Nrf2 / SIRT3 signal pathway in vascular dementia (VD) mice. Methods Wild-type mice (Nrf2+ /+ ) were divided into sham group, model group (VD group), butylphthalide treatment group (Nrf2+ /+ NBP group), and Nrf2 gene knockout mice (Nrf2-/-) were divided into Nrf2-/-model group (Nrf2-/-VD group) and Nrf2-/-treatment group (Nrf2-/-NBP group). Both the model group and the treatment group were repeated.The bilateral common carotid arteries were ligated three times to establish a mouse model of cognitive dysfunction caused by cerebral ischemia-reperfusion.The sham group only isolated the bilateral common carotid arteries and threaded the wires, but did not block blood flow.Morris water maze experiment was used to analyze the cognitive function of mice.HE staining was used to observe the changes of neuron morphology and structure in CA1 region of hippocampus, and immunohistochemical analysis was used to analyze the positive expression of caspase 3 and caspase 9 in mouse CA1 region of hippocampus.Western blot was used to detect mouse hippocampus Nrf2, p62, LC3, SIRT3 protein expression. Results (1) In Morris water maze experiment: compared with VD group, the escape latency of Sham group and Nrf2+ /+ NBP group was significantly shorter on the 5th day ((20.69±8.91) s, (7.58±9.47)s, (8.41±12.20)s; q=3.58, 5.07, both P 0.05). (2) Pathological results showed that, compared with VD group, the damage of pyramidal neurons in CA1 area of hippocampus in Sham group and Nrf2+ /+ NBP group was lighter, and that in Nrf2-/- VD group was more serious, and the improvement of neuron morphology was not obvious after NBP treatment.(3) The expression of apoptosis: compared with VD group, the expression of caspase-3 and caspase-9 in the CA1 area of hippocampus in Sham group and Nrf2+ /+ NBP group were significantly lower, and those in Nrf2-/-VD group were significantly higher (t=3.48, 2.95, 3.46, 2.93, -2.99, -3.77, all P 0.05). (4) Expression of related proteins: compared with VD group, Nrf2, SIRT3, p62 protein expression increased, LC3II/I ratio decreased in Nrf2+ /+ NBP group(t=-3.24, -4.04, -4.03, 3.62, all P<0.01); Nrf2, LC3II/ I ratio decreased, SIRT3, p62 protein expression increased in Sham group(t=3.44, 4.72, -3.52, -4.19, all P<0.01); Nrf2, SIRT3, p62 protein expression decreased and LC3II/I ratio increased in Nrf2-/-VD group(t=9.14, 4.20, 4.30, -3.78, all P<0.01); Compared with Nrf2-/- NBP, the expression of Nrf2, SIRT3, p62 decreased, and LC3II/I ratio increased in Nrf2-/-VD group(t=2.40, 3.24, 1.21, -1.16, all P<0.01). The expression of Nrf2, SIRT3, p62 protein in Nrf2+ /+ NBP group increased, and the ratio of LC3II/ I decreased (t=-3.29, -5.00, 6.24, all P<0.01). Conclusion Butylphthalide can reduce the apoptotic damage in hippocampus of VD mice and improve cognitive dysfunction caused by repeated ischemia-reperfusion injury.Regulating Nrf2 / SIRT3 pathway to inhibit hippocampal neuronal apoptosis and autophagy may be its role mechanism. Key words: Butylphthalide(NBP); Vascular dementia; Nrf2; SIRT3; Apoptosis autophagy

Effect of Hypericum Perforatum L Extracts on depression induced by chronic unpredictable mild stress in mice

Objective To observe the improving effect of Hypericum Perforatum L Extracts (HPLES)on depression induced by chronic unpredictable mild stress in mice. Methods The depression model was established by the method of chronic unpredictable mild stress. Fifty depression model mice were divided into model control group, fluoxetine hydrochloride group (2.6 mg / kg), Hypericum perforatum extract low, medium and high (0.2 g / kg, 0.4 g / kg, 0.8 g / kg) dose groups according to the random number table method. Another 10 normal mice matched with body weight were taken as the normal control group. The mice in normal control group and the model control group were given pure water by gavage every day, and the mice in other groups were given corresponding solution by gavage for 4 weeks. In addition to the normal control group, the mice in other groups continued to undergo chronic unpredictable mild stress during gavage.The sugar water preference test and forced swimming test were performed after the last administration. Blood samples were collected from the posterior orbital venous plexus, and the levels of dopamine (DA) and brain-derived neurotrophic factor (BDNF) were measured by Elisa. The hippocampal tissues of mice were examined by HE staining. Results Compared with the normal control group, the body mass of mice in the model control group decreased significantly at the first, second, third and fourth weeks (t=2.739, 4.162, 4.082, 3.957; all P 0.05). Compared with the normal control group, the sugar water preference index of mice in the model control group was significantly reduced((61.3±4.5)%, (52.6±5.2)%; t=2.721, P<0.05), the swimming immobility time was prolonged((44.3±20.00) s, (101.8±50.8) s; t=2.939, P<0.05), the difference were statistically significant. Compared with the model control group, the sugar water preference index of mice in the low, middle and high dose group of Hypericum perforatum extract increased((61.8±4.7)%, (65.2±4.1)%, (62.6±5.6)%, t=-3.005, 5.073, -2.928, all P<0.05), the swimming immobility time decreased ((47.2±17.9) s, (54.8±50.3) s, (61.3±44.2) s; t=2.803, 1.921, 1.903, all P<0.05). The results of Elisa showed that compared with the normal control group, the levels of serum DA and BDNF of mice in the model control group were significantly lower (t=3.031, 8.507, all P<0.05); compared with the model control group, the levels of serum DA of mice in the low dose and high dose group of Hypericum perforatum were significantly higher (t=5.025, 3.414, P<0.05), and the serum BDNF of mice in the high dose group of Hypericum perforatum was also significantly higher (t=6.098, P<0.05), the difference was statistically significant. HE staining showed that compared with the normal control group, the neurons in CA3 area of hippocampus in the model control group mice were seriously damaged, suggesting the establishment of the mouse model. Compared with the model control group, the atrophy and degeneration of hippocampal CA3 cells in the three dose groups were significantly reduced. The atrophy and deformation of hippocampal CA3 neurons in the low, middle and high dose groups of Hypericum perforatum extract were relieved. Conclusion HPLES have obvious improving and antidepressant effects on the depression model mice induced by chronic unpredictable stress.The above effects may be related to the improvement of serum DA, DBNF level and reduce neuronal damage in CA3 area. Key words: Hypericum perforatum L; Depression; Stress; Forced swimming; Brain-derived neurotrophic factor; Mice

Gastrin-releasing peptide inhibits CA1 neurons via increasing inhibitory synaptic transmissions in hippocampal slices of rats.

Gastrin-releasing peptide plays an important role in regulating the advanced functions of the brain including emotional behavior, learning and memory. What's more, gastrin-releasing peptide levels are also associated with the central nervous system diseases. Our previous study proposed that intraperitoneal injection of gastrin-releasing peptide can improve spatial memory in chronic ischemic model rats. It is well known that the hippocampus is an important brain area related to spatial learning and memory, but the mechanisms of gastrin-releasing peptide on hippocampal neurons are still unclear. In this study, we examined the effects of gastrin-releasing peptide on excitability of hippocampal CA1 neurons and further explored the mechanisms of its effects on synaptic transmission. The results showed that gastrin-releasing peptide inhibited the excitability of CA1 neurons and increased the amplitude and frequency of inhibitory postsynaptic currents significantly. In summary, we demonstrate that gastrin-releasing peptide can inhibit the excitability of hippocampal CA1 area neurons in brain slices and clarify the synaptic transmission mechanism involved in this process, which provide a theoretical basis for gastrin-releasing peptide to improve animal cognitive function, and new ideas for the treatment of related central nervous system diseases.

Heading direction with respect to a reference point modulates place-cell activity

The tuning of neurons in area CA1 of the hippocampus emerges through a combination of non-spatial input from different sensory modalities and spatial information about the animal’s position and heading direction relative to the spatial enclosure being navigated. The positional modulation of CA1 neuronal responses has been widely studied (e.g. place tuning), but less is known about the modulation of these neurons by heading direction. Here, utilizing electrophysiological recordings from CA1 pyramidal cells in freely moving mice, we report that a majority of neural responses are modulated by the heading-direction of the animal relative to a point within or outside their enclosure that we call a reference point. The finding of heading-direction modulation relative to reference points identifies a novel representation encoded in the neuronal responses of the dorsal hippocampus.

A Mesenchymal Stem Cell Line Transplantation Improves Neurological Function and Angiogenesis in Intraventricular Amyloid β-Infused Rats.

Mesenchymal stem cell transplantation is demonstrated to improve neurological performance in neurodegenerative diseases including Alzheimer's disease. The objective of this study is to understand the underlying mechanism of such improvement. Amyloid β (Aβ) peptide was infused into the lateral ventricle of adult Wister rats using the osmotic pump. After 15 days of continuous infusion, a mesenchymal stem cell line (B10) was transplanted in the lateral ventricle. Learning-related behavior was evaluated by 2-way shuttle avoidance test. Fifteen days after B10 transplantation, pathological and expressional changes were evaluated. Compared to sham group, learning-related behavior was significantly decreased in Aβ-infused non-transplanted group, but not in B10-transplanted group. Nissl staining results demonstrated that the number of hippocampal pyramidal neurons in CA1 area in B10-transplanted group was similar to the sham group, whereas that was decreased in Aβ-infused non-transplanted group. Aβ mainly deposited in the vessels of the brains of Aβ-infused non-transplanted rats, which was decreased by B10 transplantation. Moreover, B10 transplantation increased vessel density as well as endoglin positive cells. The number of astrocyte and microglia was decreased in Aβ-infused non-transplanted group, which was returned to the level of sham animals by B10 transplantation. Real-time PCR and immunostaining results showed that B10 transplantation significantly increased IL-1β mRNA and protein expression. Thus, our result showed that MSC transplantation effectively decreased Aβ deposition in the cerebral vessel and increased angiogenesis, which could be a possible cause of improved neurological performance in Aβ-infused AD model rats.

Effect of medicated thread moxibustion on apoptosis of hippocampal neurons in rat models of chronic cerebral ischemic vascular dementia

To investigate the effect of medicated thread moxibustion onapoptosis in hippocampal neuronsin a rat model of chronic cerebral ischemic vascular dementia. A total of 40 male Wistar rats were randomly divided into normal group and sham-operated group (7 rats each), and rat model of chronic cerebral ischemic vascular dementia (14 rats). The model group rats were treated with medicated thread moxibustion two weeks after surgery, once a day, with one day break every six days, (24 times in all)and an observation period of 4 weeks. At the end of therapy, H&amp;E staining was used to monitor changes in the neurons in CA1 area of the rat hippocampus. Changes in related indexes such as Bax, Bc1-2 and C-fos of neuron apoptosis in hippocampus CA1 area were determined by immunohistochemistry, while protein expression was semi-quantitatively assayed using imaging analysis technique. There was significant hippocampal neuronal necrosis six weeks after model establishment, but the necrosis was milder in rats in the medicated thread moxibustion group. Bax and C-fos were positively expressed and significantly higher in the hippocampus of chronic cerebral ischemic vascular dementia rats (model group) than in the medicated thread moxibustion group after treatment (p &lt;0.01). The expression of Bcl-2 was increased in the medicated thread group after treatment, and was higher in the model group, but comparable to that in the sham-operated group (p=0.975&gt;0.05). Medicated thread moxibustion alleviates hippocampal neuronal necrosis, inhibits neuron apoptosis in hippocampus CA1 area, protects nerves, and maintains relative equilibrium inBax/Bcl-2 through down-regulation of C-fos and Bax and up-regulation of Bcl-2. Thus, cell apoptosis-related pathway may be one of its mechanisms of action.

Cx36 in the mouse hippocampus during and after pilocarpine-induced status epilepticus

Gap junctions play an important role in the synchronization activity of coupled cells. Hippocampal inhibitory interneurons are involved in epileptogenesis and seizure activity, and express gap junction protein connexin (Cx) 36. Cx36 is also localized in the axons (mossy fibers) of granule cells in the dentate gyrus. While it has been documented that Cx36 is involved in epileptogenesis, there are still controversies regarding the expression levels of Cx36 at different developmental stages of human and animal models of epileptogenesis. In this study, the expression of Cx36 was investigated in the mouse hippocampus at 1 h, 4 h during pilocarpine-induced status epilepticus (PISE) and 1 week, 2 months after PISE. We found that Cx36 was down-regulated in neurons at different time points during and after PISE, whereas it was increased significantly in the stratum lucidum of CA3 area at 2 months after PISE. Double immunofluorescence indicated that Cx36 was localized in parvalbumin (PV) immunopositive interneuron in CA1 area and in mossy fibers and their terminals in the stratum lucidum of CA3 area. It suggests that decreased expression of Cx36 in interneurons may be related to less effective inhibitory control of excitatory activity of hippocampal principal neurons. However, the increased Cx36 immunopositive product in mossy fibers at the chronic stage after PISE may enhance the contacts between granule cells in the dentate gyrus and pyramidal neurons in CA3 area. The two different changes of Cx36 may be implicated in the epileptogenesis.

Mechanisms for maintaining mental maps

Neuroscience When an animal runs around, some hippocampal neurons are selectively active in specific locations called their place fields. A maplike representation created from many such place fields serves as a navigation mechanism. How such hippocampal maps stabilize is still unknown. Roux et al. investigated a discrete form of high-frequency neuronal oscillations called sharp wave ripples. In a spatial learning task, they focally silenced a subpopulation of hippocampal area CA1 neurons during sharp wave ripple events. The place fields of the silenced neurons were altered, and their spatial information content failed to increase. Control place cells, however, largely kept their spatial correlates and showed increased information after learning. Sharp wave ripple–associated neuronal firing is necessary for stabilizing and refining hippocampal place fields. Nat. Neurosci. 20 , 845 (2017).

Effects of mild hypothermia on autophagy in hippocampal CA1 neurons in rats after CPR

Objective To establish the cardiac arrest-cardiopulmonary resuscitation model in rats, and to observe the effect of mild hypothermia on autophagy in hippocampal CA1 neurons after ROSC. Methods A total of 36 Wistar rats were randomly divided into two groups: normal temperature treatment group(NT group) and mild hypothermia treatment group(HT group). To establish the cardiac arrest-cardiopulmonary resuscitation(CA-CPR) model in rats by epicardial electrical stimulation induced ventricular fibrillation, and to sacrifice 3 animals in each group to obtain the brain cortex in 2nd and 4th hours after ROSC in order to observe the expression of p-AMPK by electron microscope and LC3 granules through Western blot. The neurological deficit score(NDS) was assessed in 24、48、72 hours respectively after ROSC. To sacrifice the animals so as to take the cerebrum in 72 hours after ROSC, then calculate the apoptotic index of the hippocampal CA1 neurons, which were dyed through TUNEL method. Results The expression of p-AMPK、Beclin-1 and LC3-Ⅱ/LC3-Ⅰratio in Normothermia group were all lower than the Mild hypothermia group(P<0.05), the neurons plasma of hippocampal CA1 area in the Hypothermia group demonstrated obvious LC3 granules formation, the NDS score of the Normothermia group and the Mild hypothermia group in ROSC24h、ROSC48h、ROSC72h were 320vs205、285vs140、266vs120, respectively. The apoptotic index of the hippocampal CA1 area in the Normothemia group in ROSC72h was higher than the Mild hypothermia group, (P<0.05). Conclusions Mild hypothermia after cardiopulmonary resuscitation promotes autophagy of the hippocampal CA1 area neurons in rats and reduce neuronal apoptosis. Key words: Cardiac arrest; CPR; Mild hypothermia; Rat; Autophagy

The Effect of a Continuous Training on Necrosis and Apoptosis Changes in the Hippocampus of Diabetic Rats

Introduction: Diabetes is associated with different neurological disorders in the nervous system that will eventually lead to cell damage. The previous studies have shown the beneficial effects of exercise on brain damage caused by diabetic neuropathy in animal models. In the present study, the effect of aerobic exercise training on cell death in the hippocampal CA1 area neurons in diabetic male rats was investigated. Materials & methods: 21 adult male Wistar rats (weighing 260-300 g) were purchased from Tehran Pasteur Institute and were randomly divided into three groups: sham group, diabetic group and diabetic + exercise training group (7 rats per group). Diabetes was induced intraperitoneally streptozotocin (STZ) administration at the dose of 60mg/kg. The diabetes criterion was the blood glucose level higher than 250 mg/dl. One week after induction of diabetes, the rats in exercise training group were trained to run on a treadmill 5 days a week for 4 weeks. Necrotic cell death was detected by Nissl staining and apoptosis was detected by TUNEL staining. Findings: The results showed that aerobic exercise training significantly reduced the diabetes-induced necrotic cell death (p<0.01) and apoptosis (p<0.05) in the hippocampal CA1 area neurons. Discussion & conclusions: This study showed that aerobic exercise training has neuroprotective effects against diabetic neuropathy. This neuroprotective mechanism of exercise can be an effective way to reduce cerebral complications of diabetes.n

Ellagic acid ameliorates learning and memory deficits in a rat model of Alzheimer's disease: an exploration of underlying mechanisms.

Alzheimer's disease (AD) is a neurodegenerative disorder with irreversible loss of intellectual abilities. Current therapies for AD are still insufficient. In this study, the effect of ellagic acid on learning and memory deficits was evaluated in intrahippocampal amyloid beta (Aβ25-35)-microinjected rats and its modes of action were also explored. AD rat model was induced by bilateral intrahippocampal microinjection of Aβ25-35 and ellagic acid was daily administered (10, 50, and 100mg/kg), and learning, recognition memory, and spatial memory were evaluated in addition to histochemical assessment, oxidative stress, cholinesterases activity, and level of nuclear factor-kappaB (NF-κB), Toll-like receptor 4 (TLR4), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). The amyloid beta-microinjected rats showed a lower discrimination ratio in novel object and alternation score in Y maze tasks and exhibited an impairment of retention and recall capability in passive avoidance paradigm and higher working and reference memory errors in radial arm maze (RAM). In addition, amyloid beta group showed a lower number of Nissl-stained neurons in CA1 area in addition to enhanced oxidative stress, higher activity of cholinesterases, greater level of NF-κB and TLR4, and lower level of nuclear/cytoplasmic ratio for Nrf2 and ellagic acid at a dose of 100mg/kg significantly prevented most of these abnormal alterations. Ellagic acid pretreatment of intrahippocampal amyloid beta-microinjected rats could dose-dependently improve learning and memory deficits via neuronal protection and at molecular level through mitigation of oxidative stress and acetylcholinesterase (AChE) activity and modulation of NF-κB/Nrf2/TLR4 signaling pathway.

Corticosterone-induced changes in the inhibitory neurotransmission in hippocampal CA1 synapses depending on the activity of inhibitory synapses that express cannabinoid receptors

To study an effect of corticosterone (100 nM) on spontaneous inhibitory postsynaptic currents (sIPSC) in pyramidal neurons of CA1 area and a role of inhibitory CB1-expressing synapses in the development of corticosterone-induced effects. The experiments were performed on acute slices of the rat ventral hippocampus using whole-cell configuration of the patch-clamp technique. The addition of corticosterone resulted in a small, but significant, increase in the frequency of sIPSCs during the first 10 minutes and then this parameter returned to the basal level. Corticosterone treatment resulted in a considerable decrease in the sIPSC amplitude 40 minutes after the beginning of treatment. The activation of CB1 receptors weakly affected sIPSC characteristics, however, the addition of corticosterone did not induce the rapid elevation in the sIPSC frequency, which occurred on the 10th minute in the control, as well as a decrease in the sIPSC amplitude, which was observed in the control on the 40th min after the beginning of corticosterone treatment. The data obtained suggest that both rapid and slow effects of corticosterone are associated with the activity of CB1-expressing inhibitory synapses of the hippocampus.

Transient Oxygen/Glucose Deprivation Causes a Delayed Loss of Mitochondria and Increases Spontaneous Calcium Signaling in Astrocytic Processes.

Recently, mitochondria have been localized to astrocytic processes where they shape Ca(2+) signaling; this relationship has not been examined in models of ischemia/reperfusion. We biolistically transfected astrocytes in rat hippocampal slice cultures to facilitate fluorescent confocal microscopy, and subjected these slices to transient oxygen/glucose deprivation (OGD) that causes delayed excitotoxic death of CA1 pyramidal neurons. This insult caused a delayed loss of mitochondria from astrocytic processes and increased colocalization of mitochondria with the autophagosome marker LC3B. The losses of neurons in area CA1 and mitochondria in astrocytic processes were blocked by ionotropic glutamate receptor (iGluR) antagonists, tetrodotoxin, ziconotide (Ca(2+) channel blocker), two inhibitors of reversed Na(+)/Ca(2+) exchange (KB-R7943, YM-244769), or two inhibitors of calcineurin (cyclosporin-A, FK506). The effects of OGD were mimicked by NMDA. The glutamate uptake inhibitor (3S)-3-[[3-[[4-(trifluoromethyl)benzoyl]amino]phenyl]methoxy]-l-aspartate increased neuronal loss after OGD or NMDA, and blocked the loss of astrocytic mitochondria. Exogenous glutamate in the presence of iGluR antagonists caused a loss of mitochondria without a decrease in neurons in area CA1. Using the genetic Ca(2+) indicator Lck-GCaMP-6S, we observed two types of Ca(2+) signals: (1) in the cytoplasm surrounding mitochondria (mitochondrially centered) and (2) traversing the space between mitochondria (extramitochondrial). The spatial spread, kinetics, and frequency of these events were different. The amplitude of both types was doubled and the spread of both types changed by ∼2-fold 24 h after OGD. Together, these data suggest that pathologic activation of glutamate transport and increased astrocytic Ca(2+) through reversed Na(+)/Ca(2+) exchange triggers mitochondrial loss and dramatic increases in Ca(2+) signaling in astrocytic processes. Astrocytes, the most abundant cell type in the brain, are vital integrators of signaling and metabolism. Each astrocyte consists of many long, thin branches, called processes, which ensheathe vasculature and thousands of synapses. Mitochondria occupy the majority of each process. This occupancy is decreased by ∼50% 24 h after an in vitro model of ischemia/reperfusion injury, due to delayed fragmentation and mitophagy. The mechanism appears to be independent of neuropathology, instead involving an extended period of high glutamate uptake into astrocytes. Our data suggest that mitochondria serve as spatial buffers, and possibly even as a source of calcium signals in astrocytic processes. Loss of mitochondria resulted in drastically altered calcium signaling that could disrupt neurovascular coupling and gliotransmission.

Altered expression of neuronal CCR6 during pilocarpine induced status epilepticus in mice

Chemokine and receptor systems play important roles in different animal models of status epileptics and epileptogenesis. Here, we identified protein and gene expression of chemokine receptor 6 in the hippocampus of Swiss mice with immunohistochemistry and RT-PCR respectively. Immunohistochemical study showed that CCR6 immunopositive product was localized in different subtypes of hippocampal interneurons, in apical dendrites of pyramidal neurons of CA1 area and other laminas of the hippocampus. Strongly stained CCR6 immunopositive product was found in calbindin, calretinin, parvalbumin immunopositive interneurons in the stratum oriens of CA1 area. During pilocarpine induced status epilepticus, a transient down-regulation of neuronal CCR6 in the stratum oriens of CA1 was demonstrated at 2h during status epilepticus. The present study provides evidence that CCR6 may be involved in normal neuronal activity in the hippocampus and play an important role in maintenance of the status epilepticus.

Neuronal analysis and behaviour in prenatally gamma-irradiated rats.

The intrauterinal development in mammals represents a very sensitive period of life in relation to many environmental factors, including ionizing radiation (IR). The developing nervous system is particularly vulnerable to IR, and the consequences of exposure are of importance because of its potential health risks. The aim of our work was to assess whether prenatal irradiation of rats on the 17th day of embryonic development with a dose of 1 Gy would affect the formation of new cells and the number of mature neurons in the hippocampus and the selected forms of behaviour in the postnatal period. Male progeny of irradiated and control females was tested at ages of 3 weeks, 2 and 3 months. The number of mitotically active cells in the gyrus dentatus (GD) of the hippocampus was significantly reduced in irradiated rats aged 3 weeks. In irradiated rats aged 2 months, a significant reduction of mature neurons in CA1 area and in GD of the hippocampus was observed. The IR negatively influenced the spatial memory in Morris water maze, significantly decreased the exploratory behaviour and increased the anxiety-like behaviour in elevated plus-maze in rats aged 2 months. No significant differences were observed in animals aged 3 months compared with controls of the same age. A significant correlation between the number of mature neurons in the hilus and of the cognitive performances was found. Our results show that a low dose of radiation applied during the sensitive phase of brain development can influence the level of neurogenesis in the subgranular zone of GD and cause an impairment of the postnatal development of mental functions.

Effects of an Agonist of β2 Adrenoreceptors on Reactions of Pyramidal Neurons of Area CA1 of the Rat Hippocampus Modified Due to Blocking of GABAA Receptors

On acute slices of the rat brain, we studied, using extracellular recording of orthodromic field dischargers (OFDs), the effects of an agonist of β2 adrenoreceptors, metaproterenol (MPT), and a blocker of GABAA receptors, bicuculline; OFDs were evoked by electrical stimulation of Schaffer collaterals. Isolated application of MPT resulted in some (insignificant) trend toward increase in the intensity of OFDs of pyramidal neurons. Applications of bicuculline induced the appearance of additional spikes (two or even three) in the OFD composition. Upon simultaneous application of MPT and bicuculline, the effect of the latter was preserved and, in some cases, even noticeably enhanced. It is concluded that the agonist of β2 adrenoreceptors MPT does not counteract the events switched on after blocking of GABAA receptors and, probably, even facilitates the corresponding effects.