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PubMed2006

[Effect of polygonum multiflorum thunb on BDNF expression in rat hippocampus induced by amyloid beta-protein (Abeta) 1-40].

OBJECTIVE: To explore the effect of polygonum multiflorum thunb (PMT) on the expression of brain-drived neurtrophic factor (BDNF) in hippocampus CA1 in rats induced by Abeta1-40. METHODS: The rat model was established by injecting Abeta1-40 into the right dorsal hippocampus in rats, and their behavior was observed by Y-maze. The morphological changes of rat hippocampus were examined by the Nissl staining. The expression of BDNF in hippocampus CA1 neurons was also examined by immunohistochemistry and Western blot. RESULTS: After the administration of Abeta1-40, the times of rats learning how to elude electric stimulation were significantly increased, and the expression of BDNF in hippocampus CA1 were obviously reduced. The aggregation of Abeta1-40 in hippocampus and the morphological changes of CA1 hippocampus were found. After the treatment with PMT for 30 days, the times learning how to elude electric stimulation were obviously reduced, while the expression of BDNF in hippocampus CA1 was also increased. CONCLUSION: PMT can reverse the down-regulation of BDNF expression in hippocampus CA1 induced by Abeta1-40.

Amyloid beta-Peptides↗
PubMed1989

Glutamate decarboxylase-immunoreactive neurons are preserved in human epileptic hippocampus.

The present study was designed to determine whether inhibitory neurons in human epileptic hippocampus are reduced in number, which could reduce inhibition on principal cells and thereby be a basis for seizure susceptibility. We studied the distribution of GABA neurons and puncta by using glutamate decarboxylase (GAD) immunocytochemistry (ICC) together with Nissl stains. Using quantitative comparisons of GAD-immunoreactive (GAD-IR) neurons and puncta in human epileptic hippocampus and in the normal monkey hippocampus, we found that GAD-IR neurons and puncta are relatively unaffected by the hippocampal sclerosis typical of hippocampal epilepsy where 50-90% of principal (non-GAD-IR) cells are lost. GAD-IR neurons and puncta were not significantly decreased compared with normal monkey. In 6 patients, prior in vivo electrophysiology demonstrated that the anterior hippocampus generated all seizures. The anterior and posterior hippocampus were processed simultaneously, and the counts of hippocampal GAD-IR neurons were numerically greater in anterior than in the posterior hippocampus, where no seizures were initiated. These results indicate that GABA neurons are intact in sclerotic and epileptogenic hippocampus. Computerized image analysis of puncta densities in fascia dentata, Ammon's horn, and subicular complex in epileptic hippocampi (n = 7) were not different from puncta densities in the same regions in normal monkey (n = 2). Hence, despite the significant loss of principal cells (50-90% loss) GABA terminals (GAD-IR puncta) were normal, which suggests GABA hyperinnervation of the remnant pyramidal cells and/or dendrites in human epileptic hippocampus. The apparent increase in puncta ranged from 2 (fascia dentata) to 3.3 (CA1) times normal puncta densities. These findings would suggest increased inhibition and less excitability; however, those regions were epileptogenic. We suggest that GABA terminal sprouting or hyperinnervation of the few remnant projection cells may serve to synchronize their membrane potentials so that subsequent excitatory inputs will trigger a larger population of neurons for seizure onset in the hippocampus and propagation out to undamaged regions of subiculum and neocortex.

Animals↗
PubMed2006

Hippocampus and amygdala morphology in attention-deficit/hyperactivity disorder.

CONTEXT: Limbic structures are implicated in the genesis of attention-deficit/hyperactivity disorder (ADHD) by the presence of mood and cognitive disturbances in affected individuals and by elevated rates of mood disorders in family members of probands with ADHD. OBJECTIVE: To study the morphology of the hippocampus and amygdala in children with ADHD. DESIGN: A cross-sectional case-control study of the hippocampus and amygdala using anatomical magnetic resonance imaging. SETTINGS: University research institute. PATIENTS: One hundred fourteen individuals aged 6 to 18 years, 51 with combined-type ADHD and 63 healthy controls. MAIN OUTCOME MEASURES: Volumes and measures of surface morphology for the hippocampus and amygdala. RESULTS: The hippocampus was larger bilaterally in the ADHD group than in the control group (t = 3.35; P < .002). Detailed surface analyses of the hippocampus further localized these differences to an enlarged head of the hippocampus in the ADHD group. Although conventional measures did not detect significant differences in amygdalar volumes, surface analyses indicated the presence of reduced size bilaterally over the area of the basolateral complex. Correlations with prefrontal measures suggested abnormal connectivity between the amygdala and prefrontal cortex in the ADHD group. Enlarged subregions of the hippocampus tended to accompany fewer symptoms. CONCLUSIONS: The enlarged hippocampus in children and adolescents with ADHD may represent a compensatory response to the presence of disturbances in the perception of time, temporal processing (eg, delay aversion), and stimulus seeking associated with ADHD. Disrupted connections between the amygdala and orbitofrontal cortex may contribute to behavioral disinhibition. Our findings suggest involvement of the limbic system in the pathophysiology of ADHD.

Adolescent↗
PubMed1997

Distribution and hormone regulation of estrogen receptor immunoreactive cells in the hippocampus of male and female rats.

Estrogen regulates the synaptic plasticity and physiology of the hippocampus as well as learning behaviors that are mediated by the hippocampus. The density of dendritic spines and synapses, the number of N-methyl-D-aspartate (NMDA) binding sites, the levels of NMDA receptor subunit NR1 protein, muscimol binding to the gamma-amino butyric acid (GABA)A receptor, and levels of glutamic acid decarboxylase message in the CA1 region of the hippocampus are altered with estrogen treatment. In addition, some of these parameters exhibit sex differences in their response to estrogen treatment. To establish that estrogen can have a direct effect on the hippocampus and to determine whether or not sex differences in estrogen responsiveness are due to sex differences in estrogen receptor (ER) levels, we used immunocytochemistry with the AS409 antibody to map the location of ER-immunoreactive (ER-ir) cells in the hippocampus of male and female rats. We found that (1) the ERs appear to be in interneurons rather than pyramidal or granule cell neurons, (2) ER-ir cells are located in greatest concentration in the hilus of the dentate gyrus and the stratum radiatum of the CA1 region, (3) the density of ER-ir cells exhibits a rostral to caudal gradient in the hilus and the CA1 regions, (4) there are no sex differences in either the number or immunostaining intensity of ER-ir cells in the hippocampus, (5) the ER levels are down-regulated by estrogen in both male and female rats, and (6) the mean intensity of staining for the ER-ir cells in the hippocampus is about 25% of that in the ER-ir cells of the hypothalamus. From this, we can conclude that estrogen can have a direct effect on hippocampal neurons and that any sex differences in estrogen responsiveness is due to something other than sex differences in ER levels or function in the hippocampus.

Animals↗
PubMed1998

Lateralized fascia dentata lesion and blockade of one hippocampus: effect on spatial memory in rats.

Unilateral blockade of the dorsal hippocampus by tetrodotoxin makes it possible to form lateralized spatial memories, which rapidly transfer to the naive hippocampus when training continues with intact brain. Unilateral X-ray irradiation of newborn rats causes irreversible destruction of granule cells in the ipsilateral fascia dentata (FD). Possible compensation of poor learning in the lesioned hemisphere by commissural transfer of memories from the intact hippocampus was examined in seven rats with unilateral FD lesion, which were first trained in the Morris water maze to asymptotic performance (mean escape latency 6+/-1 s). Subsequent testing during functional ablation either of the intact or of the lesioned hippocampus by tetrodotoxin revealed escape latencies 35+/-8 s or 8+/-1 s, respectively. Probe trial tests during inactivation of the intact and lesioned hippocampus showed target quadrant preference of 32+/-2% or 54+/-3%, respectively. The results indicate: (a) that one intact hippocampus alone can support the water maze task, (b) that no, or only a very weak, memory trace is available in the lesioned hippocampus. It is concluded that the above results are due to the inability of the FD lesioned hippocampus to process the information received from the ipsilateral entorhinal cortex.

Animals↗
PubMed2000

Collateral projections from the supramammillary nucleus to the medial septum and hippocampus.

Previous reports have shown that the supramammillary nucleus projects to the medial septum and to the hippocampus, and specifically to the dentate gyrus and the CA2/CA3a region of the hippocampus. The aim of the present study was to examine collateral projections from the supramammillary nucleus to the septum and hippocampus. The fluorescent retrograde tracers, Fluororuby and Fluorogold, were injected into regions of the septum and hippocampus, respectively, and the supramammillary nucleus was examined for the presence of single- and double-labeled neurons. The main findings were: 1) pronounced numbers of single-labeled cells (about 40-60/section) were present in the supramammillary nucleus following retrograde tracer injections in either the septum or hippocampus; 2) single and double retrogradely labeled neurons were intermingled within the supramammillary nucleus and mainly localized to the lateral two-thirds of the supramammillary nucleus; 3) approximately 5-10% of supramammillary cells were double-labeled, ipsilaterally, and 2-4%, contralaterally, with injections in medial or lateral parts of the medial septum and the dentate gyrus of the hippocampus; and 4) approximately 3-5% of supramammillary cells were double-labeled, ipsilaterally, and 1-2%, contralaterally, with injections in the medial septum and CA2/CA3a of the dorsal hippocampus. Cells of the supramammillary nucleus have been shown to fire rhythmically in bursts synchronous with the hippocampal theta rhythm and have been implicated in the generation of the theta rhythm. The supramammillary cells that we identified with collateral projections to the septum and hippocampus may be directly involved in generation of the theta rhythm.

Animals↗
PubMed2001

Quantitative analysis of ER alpha and GAD colocalization in the hippocampus of the adult female rat.

Despite the many effects of estrogen in the hippocampus, there has been little evidence that hippocampal principal cells express nuclear estrogen receptors. In the hippocampus, the alpha form of the nuclear estrogen receptor (ER alpha) has been localized to sparsely distributed cells with the morphological characteristics of inhibitory interneurons. Because inhibitory neurons may be involved in the effects of estrogen on hippocampal principal cells, quantitative description of ER alpha expression in gamma-aminobutyric acid (GABA)ergic (inhibitory) and non-GABAergic cells of the hippocampus is a key step in understanding the mechanism(s) of estrogen action on hippocampal circuitry. We used single and double-label immunohistochemistry for ER alpha and glutamic acid decarboxylase (GAD; a marker of GABAergic neurons) to determine the numbers and distributions of hippocampal GABAergic and non-GABAergic neurons that express ER alpha in the adult female rat. We found many more ER alpha-expressing cells in the hippocampus than any previous study and observed distinct dorsal vs. ventral differences in hippocampal ER alpha expression. In the dorsal hippocampus, most ER alpha-positive cells were also GAD positive; however, ER alpha was expressed in only a subset of GAD-positive cells. Double-labeled cells were concentrated at the border between str. radiatum and str. lacunosum-moleculare. In the ventral hippocampus, we found a very high number of ER alpha-positive cells, the majority of which were not immunoreactive for GAD and are likely to be pyramidal cells. These findings suggest that ER alpha can mediate the effects of estrogen primarily in GABAergic neurons in the dorsal hippocampus and in both GABAergic and non-GABAergic neurons in the ventral hippocampus.

Animals↗
PubMed1984

Laminar origin and septotemporal distribution of entorhinal and perirhinal projections to the hippocampus in the cat.

The projections of the entorhinal and perirhinal cortices to the hippocampus in the cat have been studied with retrograde and anterograde tracing techniques. Retrogradely transported tracers, which were injected at different levels along the septotemporal longitudinal hippocampal axis, result in labeled neurons in superficial entorhinal cortical layers II and III. Occasionally, labeled cells were also observed in the deepest entorhinal layer as well as in the superficial layers of the perirhinal area 35. It could further be shown that labeled neurons located superficially in the entorhinal cortex are topographically distributed in a lateromedial gradient, which corresponds to a septotemporal gradient along the longitudinal axis of the hippocampus. This topographical organization of the entorhinal-hippocampal projection system could be substantiated by the use of anterograde tracing of radioactively labeled amino acids. Injections in the entorhinal cortex produce labeled fibers in the hippocampus. Injections in the perirhinal area 35 result also in labeling over the hippocampus, whereas area 36 does not seem to distribute fibers to the hippocampus. As anticipated from the results of the retrograde tracing experiments, injections located laterally, in or close to the posterior rhinal sulcus, produce prominent labeling over the septal pole of the hippocampus, whereas progressively more medially located injections result in progressively more temporally located labeling. This topographical distribution of perforant path fibers along the septotemporal axis of the hippocampus, which is related to a lateromedial axis in the entorhinal cortex, has been observed following injections in the lateral entorhinal area (LEA) as well as in the medial entorhinal area (MEA). The present observations are discussed in regard of other connectional and putative functional differences between the septal and temporal hippocampus.

Animals↗
PubMed2005

Dysregulation of memory-related proteins in the hippocampus of aged rats and their relation with cognitive impairment.

In the present experiments, we used conditioned fear to study whether changes in expression or functional state of proteins known to be involved in hippocampal learning could suggest correlation with age-related memory deficits. We focused on both alterations constitutively present in the hippocampus of aged rats and alterations related to different learning responses. Our results point at the dysregulation of the phosphorylation state of CREB in the hippocampus of aged rats as a primary biochemical correlate of their impaired memory. Other proteins, known to be important for various steps of memory formation and consolidation and linked to CREB, are to some extent altered in their constitutive expression or in the response to learning in the aged hippocampus. In particular, phosphorylated CREB and Arc, a protein functionally related to CREB in memory consolidation, are both present at constitutively higher levels in the hippocampus of aged rats, but they are not susceptible to the learning-related up-regulation occurring in young adults. Two other CREB-regulated proteins involved in memory consolidation, the neurotrophin BDNF and the transcription factor C/EBPbeta, are expressed at similar levels in the hippocampus of young-adult and aged rats, but their response to conditioned fear learning appears dysregulated by aging. Calcineurin, a protein phosphatase having CREB among its substrates and whose expression negatively correlates with learning, is more expressed in the hippocampus of aged rats. However, while calcineurin expression decreases in the hippocampus of young adults after learning, no changes are observed in the hippocampus of aged, learning-impaired rats.

Aging↗
PubMed2005

Self-motion and the origin of differential spatial scaling along the septo-temporal axis of the hippocampus.

Spatial scaling of place specific activity in the hippocampus varies systematically from the septal pole (high resolution) to the temporal pole (low resolution). Place fields get progressively larger, and the probability of observing a field in a given environment gets progressively smaller. It was previously found that decoupling movement in space from ambulation, by having the animal actively ride on a mobile platform, results in marked enlargement of the spatial scale factor in the dorsal hippocampus and a reduction in the increase in theta rhythm power with running speed, suggesting that a self-motion signal determines the spatial scale at which the hippocampal population vector updates. These results led to the hypothesis that the gain of the self-motion signal may vary systematically along the septo-temporal axis of the hippocampus. To test this hypothesis, EEG theta rhythm and ensembles of CA1 pyramidal cells and interneurons were recorded from the extreme dorsal and middle portions of the hippocampus. Pyramidal cell population vectors representing successive locations became decorrelated over substantially shorter distances in the dorsal than in the middle hippocampus. Dorsal pyramidal cells had smaller place fields, higher mean and peak firing rates, and higher intrinsic oscillation frequencies during track running than that of middle pyramidal cells. Both dorsal pyramidal cells and interneurons had more elevated mean rates during running, compared with rest, than that of the corresponding cell classes in the middle hippocampus, and both cell classes increased their rates more as a function of speed in the dorsal hippocampus.The amplitude, but not the frequency of fissure recorded theta rhythm, increased more as a function of running speed in the dorsal than in the middle hippocampus. We conclude that variation in the neuronal response to movement speed is the likely basis for the systematic variation in spatial scaling along the septo-temporal axis of the hippocampus.

Action Potentials↗
PubMed1991

On the hippocampus and learned conditional responding: effects of aspiration versus ibotenate lesions.

To study the possible involvement of the hippocampus in learned conditional responding, rats with aspiration lesions of the hippocampus and others that had the hippocampus removed with ibotenic acid were trained on concurrent Pavlovian conditional and nonconditional discriminations. In agreement with the results reported by Ross et al. (1984), animals that had the hippocampus removed with aspiration were unable to learn the conditional discrimination, but learned the simple nonconditional discrimination without difficulty. In contrast, rats that had the hippocampus removed with ibotenic acid did not differ from controls in learning either discrimination. Furthermore, transfer test results were consistent with the hypothesis that ibotenate-lesioned rats performed conditional operations to solve the conditional discrimination problem. Histological analysis indicated that the ibotenate lesions resulted in the removal of the hippocampus and dentate gyrus with minimal involvement of other structures. In aspiration hippocampal animals there was less overall damage to the hippocampus, but there was also extensive damage to the axons passing in alveus and fimbria, together with bilateral loss of cells in the subicular complex, the cingulate gyrus, and the cortex. Since rats with ibotenate lesions had more complete removal of the hippocampus, yet learned both discriminations, the impaired conditional responding found in aspiration hippocampals must be due to extrahippocampal damage.

Animals↗
PubMed2002

Postnatal development of 11beta-hydroxysteroid dehydrogenase type 1 in the rat hippocampus.

Glucocorticoids (GCs) have important actions in the hippocampus of the brain, where their access to glucocorticoid receptor (GR) is increased by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). 11beta-HSD1 converts biologically inactive 11-dehydrocorticosterone into active corticosterone. However, the postnatal development of 11beta-HSD1 in the hippocampus is not properly understood. In this study, the postnatal distribution and development of 11beta-HSD1 in the hippocampus of the rat brain was studied with immunohistochemistry and Western blot analysis. Results showed that abundant 11beta-HSD1 immunoreactive substance (ir-11beta-HSD1) was present in the hippocampus. There were homogeneous distributions of 11beta-HSD1 in the hippocampal CA1, CA2, CA3, CA4 regions and the dentate gyrus at postnatal days 1, 3, and 7. Interestingly, the developmental distribution of GR in the hippocampus followed the same pattern as 11beta-HSD1. Western blot analysis demonstrated that a higher level of expression of 11beta-HSD1 in the hippocampus was found in the first 2 weeks of life. The expressions of 11beta-HSD1 started to drop to adult levels at about postnatal day 15 both in the hippocampus and in other brain areas. These results suggest that the higher expression of 11beta-HSD1 in the neonatal hippocampus may be important for the maturation of the central nervous system mediated by GCs through GR.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed1996

Neurochemical modulation of the hippocampus in learning, remembering and forgetting in primates.

Information about the outside world is carried into the hippocampus by glutamatergic pyramidal cell pathways from the posterior association cortex via the subiculum. Processed information is carried away from the hippocampus by a reciprocal glutamatergic pathway back into posterior association cortex. These pathways are thought to be crucial for the acquisition of long term memories although it seems likely that memories are stored in cortex rather than within the hippocampus. The hippocampus is supported by functionally excitatory cholinergic modulation via fornical afferents and by functionally inhibitory serotonergic modulation specifically via 5HT1A receptors. Cholinergic modulation of the hippocampus is necessary for efficient acquisition of visuospatial tasks but not for retention of similar tasks first acquired prior to surgery. Cholinergic modulation of areas outside the hippocampus may contribute to the maintenance of memories and non-cholinergic efferents in the fornix may be required for retrieval of tasks first learnt when the hippocampus was intact. Impairments on acquisition of visuospatial tasks brought about by fornix transection can be ameliorated by direct stimulation of cholinergic receptors using pilocarpine or by blockade of the serotonergic inhibitory modulation of the hippocampus using the 5HT1A receptor antagonist, WAY100635, indicating an equal-but-opposite modulatory effect of these two neurotransmitters on hippocampal function.

Animals↗
PubMed1994

Alpha-, beta II- and gamma-subspecies of protein kinase C localized in the monkey hippocampus: pre- and post-synaptic localization of gamma-subspecies.

Protein kinase C (PKC) has attracted wide attention as a key enzyme for the expression of long-term potentiation in the hippocampus, a basic model for memory. It is of interest to study the detailed localization of PKC subspecies in the monkey hippocampus. We used immunocytochemistry to examine the localization of PKC subspecies in the hippocampus of the monkey, Macaca mulatta. Subspecies of PKC in the monkey could be separated by hydroxyapatite chromatography and the elution profile proved to be similar to that of the rat. Antibodies against each alpha, beta II and gamma-subspecies of the rat specifically reacted with the respective subspecies of monkey PKC. The alpha-, beta II- and gamma-subspecies were distinctly distributed in the hippocampus. The beta I-subspecies was not evident in the hippocampus. While both the alpha- and gamma-subspecies immunoreactive pyramidal cells were distributed throughout the hippocampus (CA1-CA3), the beta II-subspecies immunoreactive cells were scattered only in the CA1 region. The gamma-subspecies was found in granule cells and dendrites in the dentate gyrus, in mossy fibers and in their terminals in the CA3 region. The alpha-subspecies was also present in granule cells and in the dendrites but not in the mossy fibers. Glial cells did not stain with any of the antibodies used. Electron microscopy clearly showed that the gamma-subspecies was localized in both presynaptic terminals and post-synaptic dendrites. These observations suggest that subspecies of PKC in the monkey hippocampus may be involved in distinct functions and that the gamma-subspecies of PKC may act pre- and post-synaptically in pyramidal cells of the hippocampus.

Amino Acid Sequence↗
PubMed1995

Long-lasting increase in protein kinase C activity in the hippocampus of amygdala-kindled rat.

Previous studies have demonstrated that membrane-associated protein kinase C (PKC) activities in the right and left hippocampus of rats kindled from the left hippocampus increased significantly at 4 weeks [9] and 4 months [22] after the last seizure compared with those in matched control rats. In this study, we investigated the effect of kindling from the left amygdala on PKC activities in the amygdala/pyriform cortex and hippocampus at long seizure-free intervals (4 and 16 weeks) from the last amygdala-kindled seizure. Membrane-associated PKC activity of the kindled group increased significantly only in the left hippocampus compared with the left side control (the left hippocampus of rats subjected to a sham operation) at 4 weeks (by 34%, P < 0.03) and 16 weeks (by 24%, P < 0.05) after the last seizure. There was no significant alteration in the membrane-associated PKC activity of the kindled group in the right hippocampus or amygdala/pyriform cortex in any seizure-free interval after the last amygdala seizure. Cytosolic PKC activity did not differ between the kindled and control groups in any brain region examined in any seizure-free interval. At 16 weeks after the last seizure, the PKC activity in the P1 fraction of the kindled group increased significantly only in the left hippocampus (by 49%, P < 0.005), but not in the right hippocampus. Neither PKC activity in the P2 fraction nor that in the cytosolic fraction was altered in the kindled group after this seizure-free interval.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗
PubMed1993

On the role of the hippocampus in learning and memory in the rat.

An overview of lesion experiments concerned with the involvement of the hippocampus in learning and memory in the rat is presented. Multiple injections of small amounts of ibotenic acid were used to selectively remove the hippocampus (dentate gyrus, hilar cells, CA1-CA3 pyramidal cells). Similar selective, axon-sparing ibotenate lesions of hippocampus were used in a series of learning and memory experiments employing tasks that are thought to be important in hippocampal function. The performance of rats with the hippocampus removed was compared with that of control animals in the acquisition and retention of spatial versus nonspatial information, forgetting of spatial and nonspatial information, contextual learning, recognition memory and concurrent discrimination learning, and complex representational learning (conditional discrimination and negative patterning learning). The general finding that rats without a hippocampus were impaired on those tasks that required the utilization of spatial and contextual information stands in contrast with the spared performance that was found in learning about and handling (even complex) nonspatial information. Rather than support for views that emphasize a role for the hippocampus in specific memory processes (working memory, declarative memory, temporary memory buffer, configural learning), the present results are more compatible with the idea that the hippocampus plays an especially important role in processing and remembering spatial and contextual information. The limited data that are available using more selective lesions of related hippocampal formation structures (entorhinal cortex, subiculum) suggest that these structures also make important contributions to learning and memory, and that some of these contributions may be different from those made by the hippocampus.

Animals↗
PubMed2005

Patterns of hippocampal cell loss based on subregional lesions of the hippocampus.

It is widely accepted that the hippocampus plays an essential role in memory. Furthermore, studies have suggested that subregions within the hippocampus contribute differentially to specific behavioral components of memory. These studies typically rely on lesions produced by localized injections of neurotoxins (e.g., ibotenic acid or colchicine) into targeted subregions of the hippocampus. In the present study, the specificity of ibotenic acid lesions into areas CA1 and CA3 and colchicine lesions into the dorsal dentate gyrus (DG) was tested. Specifically, the effects of lesions within the dorsal hippocampus, the ventral hippocampus, and areas outside the hippocampus (e.g., lateral septum and entorhinal cortex) were evaluated using Fluoro-Jade, a histofluorescent stain for degenerating neurons. The results show that cell loss is relatively uniform after ibotenic acid injections into areas CA1 and CA3 and variable after colchicine injections into DG. CA1 and CA3 lesions appeared mostly localized to those relative subregions, and DG lesions appeared highly localized to the DG. Using these lesion procedures, little cell loss was apparent in the ventral hippocampus, and no cell loss was apparent in the entorhinal cortex. It is suggested that the lesion procedures described in this study produce relatively selective lesions of neurons within specific subregions of the hippocampus and should be useful for studies examining possible differential contributions of hippocampal subregions to memory processes.

Animals↗
PubMed2005

Hypoxic preconditioning attenuated in kainic acid-induced neurotoxicity in rat hippocampus.

The neuroprotective effect of hypoxic preconditioning on kainate (KA)-induced neurotoxicity, including apoptosis and necrosis, was investigated in rat hippocampus. Female Wistar-Kyoto rats were subjected to 380 mm Hg in an altitude chamber for 15 h/day for 28 days. Intrahippocampal infusion of KA was performed in chloral hydrate anesthetized rats, which acutely elevated 2,3-dihydroxybenzoic acid levels in normoxic rats. Seven days after the infusion, KA increased lipid peroxidation in the infused hippocampus and resulted in hippocampal CA3 neuronal loss. A 4-week hypoxic preconditioning attenuated KA-induced elevation in hydroxyl radical formation and lipid peroxidation as well as KA-induced neuronal loss. The effects of hypoxic preconditioning on KA-induced apoptosis and necrosis were investigated further. Two hours after KA infusion, cytosolic cytochrome c content was increased in the infused hippocampus. Twenty-four hours after KA infusion, pyknotic nuclei, cellular shrinkage, and cytoplasmic disintegration, but not TUNEL-positive staining, were observed in the CA3 region of hippocampus. Forty-eight hours after KA infusion, both DNA smear and DNA fragmentation were demonstrated in the infused hippocampus. Furthermore, TUNEL-positive cells, indicative of apoptosis, in the infused hippocampus were detected 72 h after KA infusion. Hypoxic pretreatment significantly reduced necrotic-like events in the KA-infused hippocampus. Moreover, hypoxic preconditioning attenuated apoptosis induced by KA infusion, including elevation in cytosolic cytochrome c content, TUNEL-positive cells, and DNA fragmentation. Our data suggest that hypoxic preconditioning may exert its neuroprotection of KA-induced oxidative injuries via attenuating both apoptosis and necrosis in rat hippocampus.

Animals↗