1-triacontanol cerotate isolated from Marsilea quadrifolia Linn. safeguards hippocampal CA3 neurons and augments special memory deficit in chronic epileptic rats / Cerotato de 1-triacontanol aislado de Marsilea quadrifolia Linn. protege las neuronas CA3 del hipocampo y mejora el déficit de memoria especial en ratas epilépticas crónicas

SUMMARY: Currently many people with epilepsy do not have seizure control even with the best available medications. Moreover various antiepileptics have adverse cognitive impact with other side effect. Thus, need for new antiepileptic drugs still remains challenge. However, many of the natural components have antiepileptic action and this fact remains scientifically unexplored. This study was designed to check the behavioral and neuro-pathological outcome of 1-Triacontanol cerotate (1TAC), isolated from Marsilea quadrifolia Linn. (MQ) on chronic Pentylenetetrazol (PTZ) kindling model of epilepsy in rats. Two-month-old adult male Wistar rats (n=60) were randomly divided into six groups; Group I (Cage Control), II (Vehicle Control), III (Positive Control), IV (Standard drug treated), V (1TAC: 40 mg/kg) & VI (1TAC: 80 mg/kg). To induce kindling a 35 mg/kg dose of PTZ was injected i.p. in every 48 hrs for 30 days in Group III to VI. Spatial memory performance was tested using Morris water maze, following which brains were further processed for histopathological investigations. Interestingly, 1TAC was able to minimize the loss of pyramidal cells in hippocampal CA3 region. These cellular changes were behaviorally responded as improved special learning and memory, a better spatial navigation and object place configuration. The current study strongly implicates that 1TAC from MQ has potent neuroprotective role and augments special memory deficit in chronic epileptic rats. The isolated component which attenuates spatial memory performance could be beneficial outcome to retain cognitive blunting in chronic epilepsy.

RESUMEN: Actualmente, muchas personas con epilepsia no cuentan con un control adecuado de las convulsiones, incluso con los mejores medicamentos disponibles. Además, varios antiepilépticos tienen un impacto cognitivo adverso además de efectos secundarios. Por lo tanto, la necesidad de nuevos fármacos antiepilépticos sigue siendo un desafío. Sin embargo, muchos de los componentes naturales tienen acción antiepiléptica y este hecho permanece científicamente inexplorado. Este estudio se diseñó para verificar el resultado conductual y neuro-patológico del cerotato de 1-triacontanol (1TAC), aislado de Marsilea quadrifolia Linn. (MQ) en el modelo de epilepsia en ratas del pentilenetetrazol (PTZ) crónico (PTZ). Ratas Wistar adultas de dos meses de edad (n = 60) se dividieron aleatoriamente en seis grupos; Grupo I (Control de jaula), II (Control de vehículo), III (Control positivo), IV (Medicamento estándar de tratamiento), V (1TAC: 40 mg / kg) y VI (1TAC: 80 mg / kg). Para inducir la inflamación se inyectó una dosis de 35 mg / kg de PTZ i.p. en cada 48 horas durante 30 días en los grupos III a VI. El rendimiento de la memoria espacial se probó utilizando el laberinto de agua de Morris, después de lo cual se procesaron los cerebros para investigaciones histopatológicas. Curiosamente, 1TAC pudo minimizar la pérdida de células piramidales en la región CA3 del hipocampo. Estos cambios celulares respondieron de manera conductual como una mejora del aprendizaje especial y la memoria, una mejor navegación espacial y la configuración del lugar del objeto. El estudio actual implica fuertemente que 1TAC de MQ tiene un potente papel neuroprotector y mejora el déficit de memoria especial en ratas epilépticas crónicas. El componente aislado que atenúa el rendimiento de la memoria espacial podría ser un resultado beneficioso para retener la reducción cognitiva en la epilepsia crónica.

Quantitative evaluation of inhibitory effects of epileptic spikes on theta rhythms in the network of hippocampal CA3 and entorhinal cortex in patients with temporal lobe epilepsy / 生理学报

Epileptic spike is an indicator of hyper-excitability and hyper-synchrony in the neural networks. The inhibitory effects of spikes on theta rhythms (4-8 Hz) might be helpful to understand the mechanism of epileptic damage on the cognitive functions. To quantitatively evaluate the inhibitory effects of spikes on theta rhythms, intracerebral electroencephalogram (EEG) recordings with both sporadic spikes (SSs) and spike-free transient period between adjacent spikes were selected in 4 patients in the status of rapid eyes movement (REM) sleep with temporal lobe epilepsy (TLE) under the pre-surgical monitoring. The electrodes of hippocampal CA3 and entorhinal cortex (EC) were employed, since CA3 and EC built up one of key loops to investigate cognition and epilepsy. These SSs occurred only in CA3, only in EC, or in both CA3 and EC synchronously. Theta power was respectively estimated around SSs and during the spike-free transient period by Gabor wavelet transform and Hilbert transform. The intermittent extent was then estimated to represent for the loss of theta rhythms during the spike-free transient period. The following findings were obtained: (1) The prominent rhythms were in theta frequency band; (2) The spikes could transiently reduce theta power, and the inhibitory effect was severer around SSs in both CA3 and EC synchronously than that around either SSs only in EC or SSs only in CA3; (3) During the spike-free transient period, theta rhythms were interrupted with the intermittent theta rhythms left and theta power level continued dropping, implying the inhibitory effect was sustained. Additionally, the intermittent extent of theta rhythms was converged to the inhibitory extent around SSs; (4) The average theta power level during the spike-free transient period might not be in line with the inhibitory extent of theta rhythms around SSs. It was concluded that the SSs had negative effects on theta rhythms transiently and directly, the inhibitory effects aroused by SSs sustained during the spike-free transient period and were directly related to the intermittent extent. It was indicated that the loss of theta rhythms might qualify exactly the sustained inhibitory effects on theta rhythms aroused by spikes in EEG. The work provided an argumentation about the relationship between the transient negative impact of interictal spike and the loss of theta rhythms during spike-free activity for the first time, offered an intuitive methodology to estimate the inhibitory effect of spikes by EEG, and might be helpful to the analysis of EEG rhythms based on local field potentials (LFPs) in deep brain.

Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis / Isoflurano fornece neuroproteção em lesão cerebral hipóxico-isquêmica neonatal por inibição da apoptose

Abstract Background and objectives: Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress. Isoflurane has shown neuroprotective properties that make a beneficial basis of using isoflurane in both cell culture and animal models, including various models of brain injury. We aimed to determine the neuroprotective effect of isoflurane on hypoxic brain injury and elucidated the underlying mechanism. Methods: A hippocampal slice, in artificial cerebrospinal fluid with glucose and oxygen deprivation, was used as an in vitro model for brain hypoxia. The orthodromic population spike and hypoxic injury potential were recorded in the CA1 and CA3 regions. Amino acid neurotransmitters concentration in perfusion solution of hippocampal slices was measured. Results: Isoflurane treatment caused delayed elimination of population spike and improved the recovery of population spike; decreased frequency of hypoxic injury potential, postponed the onset of hypoxic injury potential and increased the duration of hypoxic injury potential. Isoflurane treatment also decreased the hypoxia-induced release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but the levels of γ-aminobutyric acid were elevated. Morphological studies showed that isoflurane treatment attenuated edema of pyramid neurons in the CA1 region. It also reduced apoptosis as evident by lowered expression of caspase-3 and PARP genes. Conclusions: Isoflurane showed a neuro-protective effect on hippocampal neuron injury induced by hypoxia through suppression of apoptosis.

Resumo Justificativa e objetivos: Isoflurano é um éter volátil halogenado usado para anestesia por via inalatória. É amplamente usado na clínica como um anestésico para inalação. A lesão hipóxico-isquêmica neonatal ocorre no cérebro imaturo e resulta em morte celular tardia via excitotoxicidade e estresse oxidativo. Isoflurano mostrou ter propriedades neuroprotetoras que formam uma base benéfica para o seu uso tanto em cultura de células quanto em modelos animais, incluindo vários modelos de lesão cerebral. Nosso objetivo foi determinar o efeito neuroprotetor de isoflurano em hipóxia cerebral e elucidar o mecanismo subjacente. Métodos: Fatias de hipocampo, em fluido cerebrospinal artificial (CSFA) com glicose e privação de oxigênio, foram usadas como um modelo in vitro de hipóxia cerebral. O pico de população ortodrômica (PPO) e o potencial de lesão hipóxica (PLH) foram registrados nas regiões CA1 e CA3. A concentração de neurotransmissores de aminoácidos na solução de perfusão das fatias de hipocampo foi medida. Resultados: O tratamento com isoflurano retardou a eliminação do PPO e melhorou a recuperação do PPO; diminuiu a frequência do PLH, retardou o início do PLH e aumentou a duração do PLH. O tratamento com isoflurano também diminuiu a liberação de neurotransmissores de aminoácidos induzida pela hipóxia, como aspartato, glutamato e glicina, mas os níveis de ácido γ-aminobutírico (GABA) estavam elevados. Estudos morfológicos mostram que o tratamento de edema com isoflurano atenuou o edema de neurônios piramidais na região CA1. Também reduziu a apoptose, como mostrado pela expressão reduzida da caspase-3 e genes PARP. Conclusões: Isoflurano mostrou um efeito neuroprotetor na lesão neuronal no hipocampo induzida por hipóxia através da supressão de apoptose.

Effects of recombinant human erythropoietin on brain-derived neurotrophic factor expression in different brain regions of aging rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the effect of recombinant human erythropoietin (rhEPO) on expression of brain-derived neurotrophic factor (BDNF) in different brain regions of aging rats.</p><p><b>METHODS</b>Forty male SD rats were randomized equally into negative control group, D-galactose group, EPO treatment group, and positive control group. Rat models of subacute aging were established by continuous subcutaneous injection of 5% D-galactose. Immunohistochemical staining was used to analyze the variation of BDNF expressions in different brain regions of the aging rats with different treatments.</p><p><b>RESULTS</b>Significant brain region-specific differences in BDNF expression were found among the rats in different groups. Compared with those in the negative control group, the numbers of BDNF-positive cells in the hippocampal CA1 region, CA3 region, dentate gyrus (DG) and frontal cortex were all decreased obviously in D-galactose group (P<0.05) but increased in both EPO group and the positive control group (P<0.05) without significant differences between the latter two groups. In the rats in the same group, the number of BDNF-positive cells varied markedly in different brain regions (P<0.05), and the expression level of BDNF was the highest in the frontal cortex followed by the hippocampal CA3 region and the dentate gyrus, and was the lowest in the hippocampal CA1 region.</p><p><b>CONCLUSION</b>Treatment with rhEPO enhances the expression of BDNF in rat neural cells, suggesting that rhEPO may protect the nervous system from aging by regulating the BDNF pathway.</p>

Intracerebroventricular Kainic Acid-Induced Damage Affects Blood Glucose Level in d-glucose-fed Mouse Model

We have previously reported that the intracerebroventricular (i.c.v.) administration of kainic acid (KA) results in significant neuronal damage on the hippocampal CA3 region. In this study, we examined possible changes in the blood glucose level after i.c.v. pretreatment with KA. The blood glucose level was elevated at 30 min, began to decrease at 60 min and returned to normal at 120 min after D-glucose-feeding. We found that the blood glucose level in the KA-pretreated group was higher than in the saline-pretreated group. The up-regulation of the blood glucose level in the KA-pretreated group was still present even after 1~4 weeks. The plasma corticosterone and insulin levels were slightly higher in the KA-treated group. Corticosterone levels decreased whereas insulin levels were elevated when mice were fed with D-glucose. The i.c.v. pretreatment with KA for 24 hr caused a significant reversal of D-glucose-induced down-regulation of corticosterone level. However, the insulin level was enhanced in the KA-pretreated group compared to the vehicle-treated group when mice were fed with D-glucose. These results suggest that KA-induced alterations of the blood glucose level are related to cell death in the CA3 region whereas the up-regulation of blood glucose level in the KA-pretreated group appears to be due to a reversal of D-glucose feeding-induced down-regulation of corticosterone level.

Alteration of neural oscillations in hippocampal CA3 area in the fast avoidance response rat before and after electric shock avoidance training / 生理学报

The purpose of the present study is to explore the relationship of spatial learning ability and specific electrical activities of neural oscillations in the rat. The fast and general avoidance response groups were selected on the basis of the animals' responses to the electric shock in Y type maze, and their local field potentials (LFPs) of hippocampal CA3 area were recorded by wireless telemetry before and after shock avoidance training, respectively. The components of neural oscillations related to spatial identifying and learning ability were analyzed. The results showed that, compared with the general avoidance response group, the fast avoidance response group did not show any differences of LFPs in hippocampal CA3 area before electric shock avoidance trial, but showed significantly increased percentages of 0-10 Hz and 30-40 Hz rhythm in right hippocampal CA3 area after the shock avoidance training (P < 0.01 or P < 0.05). Fast Fourier transform showed that percentage increase of 0-10 Hz band occurred mainly in θ (3-7 Hz) frequency, and 30-40 Hz frequency change was equivalent to the γ1 band. Furthermore, compared with those before training, only the percentages of β, β2 (20-30 Hz) and γ1 rhythm increased (P < 0.01 or P < 0.05) in fast avoidance response rats after training, while the θ rhythm percentage remained unchanged. In contrast, θ rhythm percentage and the large amplitude (intensity: +2.5 - -2.5 db) θ waves in right CA3 area of general avoidance response rats were significantly reduced after training (P < 0.01). These results suggest that the increased percentages of β2 and γ1 rhythm and high-level (unchanged) percentage of θ rhythm in the right hippocampus CA3 area might be related to strong spatial cognition ability of fast avoidance response rats.

Effect of Pioglitazone on Excitotoxic Neuronal Damage in the Mouse Hippocampus

Pioglitazone (PGZ), a synthetic peroxisome proliferator-activated receptor gamma agonist, is known to regulate inflammatory process and to have neuroprotective effects against neurological disorders. In the present study, we examined the effects of 30 mg/kg PGZ on excitotoxic neuronal damage and glial activation in the mouse hippocampus following intracerebroventricular injection of kainic acid (KA). PGZ treatment significantly reduced seizure-like behavior. PGZ had the neuroprotective effect against KA-induced neuronal damage and attenuated the activations of astrocytes and microglia in the hippocampal CA3 region. In addition, MPO and NFkappaB immunoreactivities in the glial cells were also decreased in the PGZ-treated group. These results indicate that PGZ had anticonvulsant and neuroprotective effects against KA-induced excitotocix injury, and that neuroprotective effect of PGZ might be due to the attenuation of KA-induced activation in astrocytes and microglia as well as KA-induced increases in MPO and NFkappaB.

Housing under the pyramid reduces susceptibility of hippocampal CA3 pyramidal neurons to prenatal stress in the developing rat offspring.

Mother-offspring interaction begins before birth. The foetus is particularly vulnerable to environmental insults and stress. The body responds by releasing excess of the stress hormone cortisol, which acts on glucocorticoid receptors. Hippocampus in the brain is rich in glucocorticoid receptors and therefore susceptible to stress. The stress effects are reduced when the animals are placed under a model wooden pyramid. The present study was to first explore the effects of prenatal restraint-stress on the plasma corticosterone levels and the dendritic arborisation of CA3 pyramidal neurons in the hippocampus of the offspring. Further, to test whether the pyramid environment would alter these effects, as housing under a pyramid is known to reduce the stress effects, pregnant Sprague Dawley rats were restrained for 9 h per day from gestation day 7 until parturition in a wire-mesh restrainer. Plasma corticosterone levels were found to be significantly increased. In addition, there was a significant reduction in the apical and the basal total dendritic branching points and intersections of the CA3 hippocampal pyramidal neurons. The results thus suggest that, housing in the pyramid dramatically reduces prenatal stress effects in rats.

Effect of limb ischemic preconditioning on the expression of p38 MAPK and HSP 70 in CA3 and DG regions of the hippocampus of rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the expression of p38 MAPK and HSP 70 in CA3 and dentate gyrus (DG) regions of the hippocampus of rats induced by limb ischemic preconditioning (LIP).</p><p><b>METHODS</b>Ninety-six rats were randomly divided into sham and LIP groups. And the animals in the LIP group were further divided into LIP 6 h, LIP 12 h, LIP 1 d, LIP 2 d, LIP 3 d, LIP 4 d and LIP 5 d subgroups according to the time of reperfusion after LIP. Immunohistochemical staining and Western blot were used to observe the expression of p38 MAPK and HSP 70 in CA3 and DG regions of the hippocampus.</p><p><b>RESULTS</b>The results of the immunohistochemical staining and Western blot were consistent, which indicated that there were fluctuation in the p-p38 MAPK and HSP 70 expression in CA3 and DG regions after LIP compared with those of the sham group. The expression of p-p38 MAPK began to be up-regulated 1d after LIP and reached its peak at 3 d and lasted for 4 d after LIP. However, the expression of HSP 70 was significantly up-regulated 2 d after LIP compared to the sham group, reached its peak at 3 d and lasted until the 4 d after LIP.</p><p><b>CONCLUSION</b>LIP up-regulates the expression of p38 MAPK and HSP 70 in the CA3 and DG regions of the hippocampus of rats.</p>

Effect of Naoling decoction on the expression of microglia and IL-6 in hippocampal CA3 region of rats with synthetic Alzheimer's disease / 中南大学学报(医学版)

OBJECTIVE@#To observe the effect of Naoling decoction on the learning and memory behaviors and the expression of microglia and IL-6 in hippocampal CA3 region of rats with Alzheimer's disease (AD), and to elucidate the potential mechanism.@*METHODS@#Thirty SD rats were randomly divided into 5 groups: a normal group, a sham-operation group, an AD group, a Naoling decoction group and a Naofukang group. The spatial learning and memory behaviors of the rats were investigated by water maze and Y-maze. The Alzheimer's disease model was established by injecting Aβ1-42 into the hippocamal of the rats. Expression of OX-42 (one of the microglia specific markers) and IL-6 in the CA3 region of hippocamal was measured by immunohistochemical stain.@*RESULTS@#Morris water maze experiment showed that the escape latency of hidden platform in the AD group was significantly delayed (P<0.05) and the average times of passing was decreased (P<0.05). Y-maze test showed that the times needed to the learn how to evade the electrical stimulation in the AD group was most than in other groups (P<0.05). Compared with the AD group, the Morris water maze test and Y-maze test of the Naoling decoction group were significantly different (P<0.05). The expression of OX-42 and IL-6 in the CA3 region of hippocamal in the Naoling decoction group was decreased (P<0.05).@*CONCLUSION@#Naoling decoction can improve learning and memory, and weaken the expression of OX-42 and IL-6 in hippocampal CA3 of AD rats, which may partly be the therapeutic mechanism of Naoling decoction for AD.

Division of CA1, CA3 and DG regions of the hippocampus of Wistar rat / 中国应用生理学杂志

<p><b>OBJECTIVE</b>Division of the CA1, CA3 and dentate gyrus (DG) regions of the hippocampus of Wistar rat under the stereomicroscope.</p><p><b>METHODS</b>Twenty-four Wistar rats were randomly assigned to three groups. (1) The brain was sectioned coronally (n = 6). The sections were stained with thionin and the morphology of cells in each region of the hippocampus was observed under microscopy. (2) The hippocampus was dissected out and observed on the whole. Then, the CA1, CA3 and DG regions of the hippocampus were divided. Every region divided was sectioned, and the morphology of cells was observed. (3) Rats with brain ischemia or not were also decapitated and the HSP 70 expressions were observed in CA1, CA3 + DG regions by Western blot and immunohistochemical staining (n = 12).</p><p><b>RESULTS</b>(1) The CA1, CA3 and DG regions of the hippocampus could be clearly observed in coronal section of the brain stained by thionin. (2) Under the stereomicroscope, the CA1 and DG regions of the hippocampus could be separated along the hippocampal fissure between them in ventral surface of the hippocampus. The CA3 and DG regions of the hippocampus could be separated along a fissure between them. The appearance of cells in the sections of the divided CA1, CA3 and DG specimens is consistent with that in the brain coronal sections, respectively. (3) The results of Western blot indicated that the HSP 70 expression of the brain ischemia group was up-regulated significantly in CA3 + DG regions compared with the sham group. However, HSP 70 expression has no significant changes in CA1 region. The above results were consistent with those of the immunohistochemical staining.</p><p><b>CONCLUSION</b>The CA1, CA3 and DG regions of the hippocampus of Wistar rat could be divided under stereomicroscope, and the divided each region was sensible for detection of protein using Western blot.</p>

Effect of Shuganjieyu capsules on neuronal apoptosis in hippocampal CA3 area and the expression of caspase-3 in the brain of rat depression model / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the effect of "Shuganjieyu" (SGJY) capsules on neuronal apoptosis in hippocampal CA3 area and the expression of caspase-3 in the brain of rat depression model, and to investigate its pharmacological mechanisms in depression treatment.@*METHODS@#Adult male SD rats were randomly divided into 4 groups: a control, a model, a SGJY and a fluoxetine group. The rat depression model was established under chronic unpredictable mild stress (CUMS) and separate feeding. The behaviors were measured by open-field test, sucrose consumption and forced swimming test. We observed the neuronal morphology structure and neuronal apoptosis in the hippocampal CA3 area. We detected the rat caspase-3 expression level of medial prefrontal cortex ( mPFC) and hippocampal CA3 area by Western blot.@*RESULTS@#After 21-day stress, compared with the model group, spontaneous activity and sucrose consumption and preference percentage of the rats in the SGJY group significantly increased, while the immobility time in forced swimming test, the number of apoptotic cells and the protein levels of caspase-3 significantly reduced (P0.05).@*CONCLUSION@#SGJY capsules can reduce the depression symptoms of CUMS and help to increase hippocampal neuron generation, survival and neogenesis, reduce the protein levels of caspase-3, and reverse neurocyte apoptosis in the rat depression model with the same efficacy as fluoxetine.

Delivery of epidermal neural crest stem cells [EPI-NCSC] to hippocamp in Alzheimer's disease rat model

Alzheimer's disease [AD] is characterized by progressive neuronal loss in hippocamp. Epidermal neural crest stem cells [EPI-NCSC] can differentiate into neurons, astrocytes and oligodendrocytes. The purpose of this study was to evaluate the effects of transplanting EPI-NCSC into AD rat model. Two weeks after induction of AD by injection of Amyloid-beta 1-40 into CA1 area of rat hippocamp, Y-maze and single-trial passive avoidance tests were used to show deficit of learning and memory abilities. EPI-NCSC were obtained from the vibrissa hair follicle of rat, cultured and labeled with bromodeoxyuridine. When Alzheimer was proved by behavioral tests, EPI-NCSC was transplanted into CA3 area of hippocamp in AD rat model. The staining of EPI-NCSC markers [nestin and SOX10] was done in vitro. Double-labeling immunofluorescence was performed to study survival and differentiation of the grafted cells. We showed that transplanted EPI-NCSC survive and produce many neurons and a few glial cells, presenting glial fibrillary acidic protein. Total number of granule cells in hippocamp was estimated to be more in the AD rat model with transplanted cells as compared to AD control group. We observed that rats with hippocampal damage made more errors than control rats on the Y-maze, when reward locations were reversed. Transplanted cells were migrated to all areas of hippocamp and the total number of granule cell in treatment group was equal compared to control group. Transplantation of EPI-NCSC into hippocamp might differentiate into cholinergic neurons and could cure impairment of memory in AD rat model

[Effect of gestational diabetes on astrocyte density in CA1 and CA3 subfields of hippocampus in rat offspring]

Diabetes mellitus is one of the most common serious metabolic disorders characterized by hyperglycemia, altered metabolism of lipids, carbohydrates and proteins. Gestational diabetes mellitus [GDM], affects 3.5-5% of all human pregnancy. Therefore, this study was done to evaluate the effect of gestational diabetes on astrocyte density in CA1 and CA3 subfields of hippocampus in rat male offspring. In this experimental study, 12 Wistar Dams rats were randomly allocated in control and diabetic groups. Gestational diabetes induced by 40 mg/kg/body weight of streptozotocin at the first day of gestation [GD] in experimental group and controls were received an equivalent volume normal saline injection intraperitoneally [IP]. Six male offspring of cases and controls dams, at the 7, 21 postnatal day [P7, P21] were randomly selected. Animals were scarified using chloroform anesthesia. The coronal sections of brain by 6 micrometer serially were prepared. The sections were stained with PTAH. The number of astrocytes was evaluated in 100000 micro m[2] area of CA1 and CA3 in 1000X magnification. Data was analyzed by SPSS-11.5 and t-test. In CA1 subfield of hippocampus in offspring, the number of astrocytes significantly reduced by 36.25% and 36.37% in diabetic group in compare to controls in the P7 and P21, respectively [P<0.05]. In CA3, astrocytes density significantly reduced 36.35% and 26.5% in GD in comparison with controls in the P7 and P21, respectively [P<0.05]. This study showed that the uncontrol gestational diabetes significantly reduces astrocytes density in CA1 and CA3 subfields of hippocampus in rat offspring

Microglial Expression of Phospho-AMP-Activatd Protein Kinase (AMPK) Following an Excitotoxic Lesion in the Mouse Hippocampus / 대한해부학회지

AMP-activatied protein kinase (AMPK) is a member of the family of serine/threonine kinases and is activated by cellular ATP/AMP ratio under conditions of nutritional/metabolic stress. This is thus often referred to as the fuel gauge of the cell, since it protects the cell against ATP depletion and boosts the energy generation pathway. However, although several studies have been focused on the AMPK in other organs, little is known about AMPK expression in glial cells under neuropathological conditions. In this study, we examined patterns of phospho-AMPKalpha expression following the induction of an excitotoxic lesion in mouse brain by kainic acid (KA) injection, which caused pyramidal cell degeneration and intense glial reaction in the hippocampal CA3 region. Phospho-AMPKalpha immunoreactivity was observed in migcroglia, not astrocytes throughout the CA3 region in parallel with pyramidal cell degeneration. These data suggest that AMPK may play an important role in the regulation of energy metabolism of microglial activation in response to the inflammatory processes by excitotoxic injuries.

Effects of yi-zhi II on synaptic structure of hippocampal CA3 and maintenance of memory / 中国应用生理学杂志

<p><b>AIM</b>To study the effects of yi-zhi II (a compond of Chinese Traditional Medicine) on the alteration of synaptic structure in hippocampal CA3 and maintenance of memoy.</p><p><b>METHODS</b>By using the method of oral administration of yi-zhi II, the step-through test and electron microscopy, the latency of step-through and synaptic structure in hippocamal CA3 were tested.</p><p><b>RESULTS</b>(1) The mice which had been given yi-zhi II prolong significantly the latency of step through (P < 0.05 or P < 0.01) on the 1st, 6th and 12th day after learning. (2) On the 6th and 12th day after learning, the length of synaptic active zone were markly improved in yi-zhi II and control, but that of yi-zhi II was better than that of control. (On the 6th day after learning, the number of perforated synapses and axo-dendrite synapses were significantly improved by the yi-zhi II (P < 0.05).</p><p><b>CONCLUSION</b>The yi-zhi II could improve the learning and memory in mice. It migth improve the memory by increasing the length of synaptic active zone and the number of perforated synapses and axo-dendrite synapses in hippocampal CA3.</p>

Effects of beta-cypermethrin on voltage-gated potassium channels in rat hippocampal CA3 neurons / 生理学报

The effects of beta-cypermethrin (consisting of alpha-cypermethrin and theta-cypermethrin) on the transient outward potassium current (I(A)) and delayed rectifier potassium current (I(K)) in freshly dissociated hippocampal CA3 neurons of rats were studied using whole-cell patch-clamp technique. The results indicated that alpha-cypermethrin increased the value of I(A) and theta-cypermethrin decreased the value of I(A), though both of them shifted steady activation curve of I(A) towards negative potential. theta-cypermethrin contributed to the inactivation of I(A). The results also showed that alpha-cypermethrin and theta-cypermethrin decreased the value of I(K), and shifted the steady state activation curve of I(K) towards negative potential. Both alpha-cypermethrin and theta-cypermethrin had no obvious effects on the inactivation of I(K). theta-cypermethrin prolonged recovery process of I(K). These results imply that both transient outward potassium channels and delayed rectified potassium channels are the targets of beta-cypermethrin, which may explain the mechanism of toxical effects of beta-cypermethrin on mammalian neurons.

Effect of ketogenic diet on hippocampus synaptic reorganization and GluR5 expression in kainic acid induced rat model of epilepsy / 中华儿科杂志

<p><b>OBJECTIVE</b>Ketogenic diet (KD) is a high fat, low protein, low carbohydrate diet. Its antiepileptic effect is certain but the underlying mechanism is unknown. The aim of the study was to reveal the possible mechanism from the view points of synaptic reorganization and GluR(5) expression in hippocampus.</p><p><b>METHODS</b>Epilepsy was induced in Sprague-Dawley rats by kainic acid at postnatal day 28, all control animals were fed with normal rodent chow, whereas experimental rats were fed with ketogenic feed for 8 weeks. Spontaneous recurrent seizures were recorded. Mossy fiber sprouting and neuron damage in hippocampus were investigated by Timm staining and Nissl staining. Western blot and RT-PCR methods were applied to detect the expression of GluR(5) and GluR(5) mRNA in hippocampus.</p><p><b>RESULTS</b>KD-fed rats (1.40 +/- 1.03) had significantly fewer spontaneous recurrent seizures than control diet-fed rats (7.36 +/- 3.75). The mean A of mossy fiber sprouting in the inner molecular layer of dentate gyrus was markedly higher in KA induced animals than that in saline control animals but it was similar in different diet fed groups. No significant differences were found in the mean A of Timm staining in CA(3) area and Nissl staining of neuron in hilus, CA(3) and CA(1) area. After KA kindling, KD-fed animals [(189.38 +/- 40.03)/mg pro] had significantly higher GluR(5) expression in hippocampus than control diet-fed animals [(128.79 +/- 46.51)/mg pro] although their GluR(5) mRNA was the same.</p><p><b>CONCLUSION</b>Mossy fiber sprouting may be responsible for epileptogenesis in KA induced model and KD can suppress seizures in these animals. KD may upregulate young rat GluR(5) in inhibitory interneurons of CA(1) thus lead to an increased inhibition to prevent the propagation of seizure.</p>

Effects of melatonin on the induction of long term potentiation in the hippocampal CA3 area of rats / 中国应用生理学杂志

<p><b>AIM</b>To study the effect of melatonin on the induction of LTP in CA3 area of hippocampus and to investigated its possible mechanisms.</p><p><b>METHODS</b>Melatonin and other drugs (Tacrine or DNQX) were microinjected into the CA3 area. By using extracellular electrophysiological recordings to observe the changes of the slope of fEPSP in the CA3 area.</p><p><b>RESULTS</b>(1) Evoked potential and the induction of LTP were depressed by different concentration of melatonin (0.2 microg/microl, 1 microg/microl and 5 microg/microl). As the melatonin concentration increased, the induction of LTP was blocked more obviously. (2) Melatonin could attenuate the excitation effect of Tacrine (inhibitor of AChE) on LTP. (3) Inhibition of the melatonin-induced on LTP attenuated by DNQX.</p><p><b>CONCLUSION</b>The application of melatonin in rats inhibits the induction of LTP in the hippocampal CA3 area. The action of melatonin on the induction of LTP may be through the modulation of not only non-NMDA receptors but also cholinergic system.</p>

Effects of fimbria/fornix transection on rat's synaptic configuration of hippocampus CA3 area / 中国应用生理学杂志

<p><b>AIM</b>To observe the effect of fimbria-fornix (FF) transection on rat's hippocampal synaptic configuration.</p><p><b>METHODS</b>Animal models were produced by transecting rat's bilateral fimbria-fornix (FF). Y-type maze test were carried out respectively before and after the models were built, and emphasis was laid on the quantitative analyses of the parameters of synapses in the hippocampal CA3 areas.</p><p><b>RESULTS</b>The thickness of postsynaptic density material, the curvature of synaptic interface and the occurrence of perforated synapses decreased, while the width of synaptic cleft increased.</p><p><b>CONCLUSION</b>Fimbria-fornix transection resulted in evident changes of the synaptic configuration in the hippocampal CA3 areas and we presume that the normal Ach level in the hippocampus plays a key role in maintaining the normal synaptic interface ultrastructure of the hippocampus CA3 area.</p>