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PubMed2001

Involvement of dopamine D(2) receptors in complex maze learning and acetylcholine release in ventral hippocampus of rats.

In the current study we focus on the involvement of dopamine D(2) receptors in the ventral hippocampus in memory performance and acetylcholine release. Using the aversively motivated 14-unit T-maze (Stone maze) the injection of raclopride, a D(2) receptor antagonist, into the ventral hippocampus (8 microg/kg) was found to impair memory performance. Co-injection of quinpirole, a D(2) receptor agonist (8 microg/kg), overcame the impairment in performance. Microdialysis study revealed that quinpirole infusion (10-500 microM) into the ventral hippocampus stimulated acetylcholine release in a dose-dependent manner, and systemic injection of quinpirole (0.5 mg/kg, i.p.) also stimulated acetylcholine release in the ventral hippocampus. Infusion of eticlopride, another D(2) receptor antagonist, into the ventral hippocampus suppressed acetylcholine release in the hippocampus induced by systemic injection of quinpirole. Taken together, we suggest that D(2) receptors in the ventral hippocampus are involved in memory performance, possibly through the regulation of acetylcholine.

Acetylcholine↗
PubMed2001

Evidence of functional vitamin D receptors in rat hippocampus.

The steroid hormone vitamin D has important biological roles in calcium transport, cell growth, and cell differentiation. Its cellular activities are mediated by high affinity interaction with the vitamin D receptor. In brain, autoradiographic, immunohistologic, and messenger RNA expression studies implicate a number of neuronal systems, including the hippocampus, as potential targets of vitamin D. However, cellular distribution and protein expression, and binding of the receptor to vitamin D response elements have yet to be established in hippocampus. This investigation was undertaken to characterize the vitamin D receptor in rat hippocampus with western blot, immunocytochemistry, and gel shift analyses. The presence of the receptor protein in hippocampus extracts was revealed with western blotting using an anti-rat vitamin D receptor antiserum. In vivo and in vitro immunocytochemical results confirmed the presence of vitamin D receptor in neuronal and glial cells. In the hippocampus, the receptor was localized in pyramidal and granule cell layers, CA1, CA2, and CA3 subfields and in the dentate gyrus. Double labeling for the vitamin D receptor and glial fibrillary acidic protein revealed that glia also expressed the receptor protein. Gel shift analyses evaluated with the murine osteopontin vitamin D response element indicated a specific, bound receptor-containing complex from hippocampal extracts. Altogether, these findings clearly document the localization of vitamin D receptor in rat hippocampus and that hippocampus contains vitamin D receptors capable of specifically binding to DNA. In combination with reports of a neuroprotective role for vitamin D in hippocampal cell survival, these data suggest that the endogenous vitamin D receptor may mitigate processes related to cellular homeostasis, perhaps through a calcium buffering mechanism.

Animals↗
PubMed2002

Grafts of fetal septal cells after cholinergic immunotoxic denervation of the hippocampus: a functional dissociation between dorsal and ventral implantation sites.

Three-month-old Long-Evans rats were subjected to intraseptal infusions of 0.8 microg of 192 IgG-saporin followed, 2 weeks later, by intrahippocampal suspension grafts containing fetal cells from the medial septum and the diagonal band of Broca. The suspensions were implanted in the dorsal or the ventral hippocampus. Sham-operated and lesion-only rats were used as controls. Between 18 and 32 weeks after grafting, all rats were tested in a water maze (using protocols placing emphasis on reference memory or on working memory) and an eight-arm radial maze. The lesion produced extensive cholinergic denervation of the hippocampus, as evidenced by reduced acetylcholinesterase-positivity and acetylcholine content. Depending upon their implantation site, the grafts restored an acetylcholinesterase-positive reinnervation pattern in either the dorsal or the ventral hippocampus. Nevertheless, the grafts failed to normalize the concentration of acetylcholine in either region. The cholinergic lesion impaired working memory performance in both the water maze and the radial maze. To a limited degree, reference memory was also altered. Grafts placed in the ventral hippocampus had no significant behavioral effect, whereas those placed in the dorsal hippocampus normalized working memory performance in the water maze. Our data show that infusion of 192 IgG-saporin into the septal region deprived the hippocampus of its cholinergic innervation and altered spatial working memory more consistently than spatial reference memory. Although the cholinergic nature of the graft-induced reinnervation remains to be established more clearly, these results further support the idea of a functional dissociation between the dorsal and the ventral hippocampus, the former being preferentially involved in spatial memory.

Animals↗
PubMed1997

Cholinergic deafferentation exacerbates seizure-induced loss of somatostatin-immunoreactive neurons in the rat hippocampus.

The loss of somatostatin-immunoreactive neurons and the sprouting of mossy fibers are typical histopathological abnormalities in the hippocampus in experimental and human temporal lobe epilepsy. To investigate whether the development of seizure-induced alterations is regulated by the subcortical afferent pathways to the hippocampus, we lesioned cholinergic, noradrenergic or serotonergic afferent pathways in rats two days after seizures were induced with kainate. Two months later, somatostatin-immunoreactive neurons were counted in the hilus to assess the severity of neuronal damage. Mossy fiber sprouting was analysed from adjacent Timm-stained sections. Kainate-induced seizures caused a loss of hilar somatostatin-immunoreactive neurons in the septal end of the hippocampus, where 63% of the somatostatin-immunoreactive neurons survived. Even more severe damage was found in the temporal end of the hippocampus (only 21% surviving). Cholinergic deafferentation of the hippocampus (using 192-IgG saporin) decreased the overall number of hilar somatostatin-immunoreactive neurons. In control rats that did not receive kainate, 87% (septal end) and 74% (temporal end) of the hilar somatostatin-immunoreactive neurons remained after cholinergic deafferentation. Moreover, seizure-induced damage to hilar somatostatin-immunoreactive neurons was further exacerbated by 192-IgG-saporin, with only 35% of the neurons remaining in the septal end and 14% in the temporal end of the hippocampus. Noradrenergic [using N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine] or serotonergic (using 5,7-dihydroxytryptamine) lesions did not affect the number of hilar somatostatin-immunoreactive neurons either in control or in kainate-treated rats. The severity and distribution of seizure-induced mossy fiber sprouting were also not affected by any of the lesions. These data suggest that various subcortical afferent pathways may differentially modulate seizure-induced damage to the hippocampus. Damage to cholinergic neurons results in the loss of hilar somatostatin-immunoreactive neurons and exacerbates the seizure-induced loss of somatostatin-immunoreactive neurons.

Afferent Pathways↗
PubMed2000

Expression of mRNAs encoding for 17beta-hydroxisteroid dehydrogenase isozymes 1, 2, 3 and 4 in epileptic human hippocampus.

Sex steroid hormones exert important influences on neuroendocrine and behavioural brain function. As neuroactive steroids they are able to modify neuronal excitability. Unbalanced synthesis may thus be implicated in pathophysiological conditions, such as epilepsy, migraine, depression and anxiety. In sex steroid metabolism, 17beta-hydroxisteroid dehydrogenases (17beta-HSDs) play a crucial role in catalyzing the final steps of androgen and estrogen biosynthesis. The hippocampus appears to be a major target area of neurosteroidal action. The expression of 17beta-HSD isozymes has not yet been studied in human hippocampus. Therefore, we investigated the expression of 17beta-HSD 1, 2, 3 and 4 mRNAs in hippocampal tissue specimens obtained at neurosurgery from 42 patients with pharmacoresistant temporal lobe epilepsy. A competitive RT-PCR assay was used to quantify the mRNA transcript level. 17beta-HSD 1 mRNA concentrations were 10000 fold lower in the hippocampus compared to placental tissue, whereas 17beta-HSD 3 mRNA concentrations were 50 fold lower than in testis and 17beta-HSD 4 concentrations were in the same order of magnitude as in liver. 17beta-HSD 2 mRNA was not expressed. 17beta-HSD 1, 3 and 4 mRNA concentrations in the hippocampus showed no significant differences between men and women and there were no significant differences in expression levels of these enzymes between patients with Ammon's horn sclerosis (AHS) and those with histopathologically normal hippocampus associated with extrahippocampal lesions. No significant correlation could be detected between duration of epilepsy, individual seizure frequency and expression levels of 17beta-HSDs. In conclusion, the present study is the first to demonstrate mRNA expression of 17beta-HSD 1, 3 and 4 in the epileptic human hippocampus. Together with data on 5alpha-reductase 1, 3alpha-hydroxisteroid oxidoreductase 2 and cytochrome P450scc, previously shown to be expressed in the human hippocampus also, our data provide further evidence for the existence of sex steroid formation and metabolism in this specific brain area.

17-Hydroxysteroid Dehydrogenases↗
PubMed1999

Neuronal firing activity in the dorsal hippocampus during the auditory discrimination oddball task in awake rats: relation to event-related potential generation.

In order to investigate the roles of the hippocampus in event-related potential (ERP) generation, extracellular neuronal firings in the dorsal hippocampus were recorded together with the ERPs on the cortical surface and at the hippocampus during the auditory discrimination task in awake rats. The major ERP components on the cortical surface in response to the target tone were the P2, N2, and P3 with the latencies being approximately 100, 200 and 450 ms, respectively. For the non-target tone, the N2 and P3 components were not clearly observed. Local ERP at the hippocampus exhibited similar wave-forms to that on the cortex in response to the target and non-target tones. In the hippocampus, 11 of 21 neuronal firings showed a long-latency sustained activation from 113.6+/-89.7 ms to 539.1+/-208.6 ms with the peak being 281.6+/-167.4 ms after the target tone onset. This increase was not observed after the non-target tone, and was not prominent when the rat did not perform the task. It was not time-locked to lever pressing behavior, and was not affected by the intensity of the tone stimulus. These features in relation to behavioral and paradigm indices were similar to the long-latency ERP components, N2 and P3. Possible involvement of the hippocampus in ERP generation was further suggested by the correlation between the magnitude of the long-latency activation and the amplitudes of N2 and P3 in some hippocampal firings. On the other hand, seven neuronal firings showed a short-latency transient activation with the peak at 36.3+/-14.4 ms accompanied by the early components of local ERP in the hippocampus both after the target and non-target tones. This response was more conspicuous when the rat did not perform the task and its amplitude was positively affected by the stimulus intensity. These findings imply that there are two types of hippocampal neuronal activation during the auditory discrimination oddball task. One is the short-latency activation that is related to information processing of the exogenous stimulus property. The second is the long-latency activation that may be involved in execution of the cognitive task, and in generation of long-latency ERP components.

Animals↗
PubMed1994

Ontogeny of kainate-induced gene expression in rat hippocampus.

The ontogeny of kainate induction of AP-1 mRNAs, proteins, and DNA binding activities was examined in the rat hippocampus. In addition, kainate induction of preproenkephalin and preprodynorphin mRNAs was examined; these genes have been shown to be induced by kainate and have been suggested to be targets of AP-1 regulation in adult rat hippocampus. Despite producing seizures at postnatal day (P) 7, kainate failed to induce AP-1 or opiate gene expression and did not increase AP-1 DNA binding activity at this age. Basal levels of AP-1 and opiate mRNAs were low in P7 hippocampus. Basal levels of c-jun protein and AP-1 DNA binding activity were elevated in the P7 hippocampus, to values greater than induced levels in adult hippocampus. Furthermore, AP-1 DNA binding in P7 hippocampal nuclear extract was unaffected by antibodies against fos-related antigens, in contrast to hippocampal extracts from the older rats examined. At P14, induction of AP-1 and preproenkephalin (but not preprodynorphin) mRNAs was observed with kainate treatment, but the time course for inductions was delayed relative to kainate inductions in the adult hippocampus. At P21, responses to kainate were similar to the adult response. Unlike in adult hippocampus, seizure activity caused by kainate treatment does not increase the transcription factor and opioid peptide gene expression in the hippocampi of P7 rats.

Animals↗
PubMed1995

Persistent translocation and inhibition of Ca2+/calmodulin-dependent protein kinase II in the crude synaptosomal fraction of the vulnerable hippocampus following hypoglycemia.

Alterations in the levels and activity of Ca2+/calmodulin-dependent protein kinase II (CaM-kinase II) were studied in the rat hippocampus during and after insulin-induced hypoglycemic coma. A permanent loss of CaM-kinase II immunohistostaining in the neuronal layer begins at 10 min of isoelectricity in the tip of the dentate gyrus and at 30-min isoelectricity in the CA1 region. The reduction in immunohistostaining in the neurites is less pronounced. Immunoreactivity of CaM-kinase II on western blots increases in the crude synaptosomal fractions and decreases in cytosolic fraction, indicative of a translocation of CaM-kinase II. The translocation persists for at least 1 day of recovery after 30 min of isoelectricity in the vulnerable hippocampus (dorsomedial hippocampus) but not in the resistant hippocampus (dorsolateral hippocampus). Calmodulin binding to western blots shows changes similar to the immunoblots. Ca2+/calmodulin-dependent activity of CaM-kinase II in the crude synaptosomal fraction is elevated immediately before isoelectricity and is then inhibited during and after 30 min of isoelectricity, despite the increase of CaM-kinase II immunoreactivity. This was seen in the vulnerable hippocampus. The data indicate that stimulus of translocation and inhibition of CaM-kinase II persist during the recovery phase, preceding neuronal degeneration in the vulnerable hippocampus. This may be of significance for hypoglycemia-induced neuronal death.

Animals↗
PubMed1997

Differential regulation by methylenedioxymethamphetamine of 5-hydroxytryptamine1A receptor density and mRNA expression in rat hippocampus, frontal cortex, and brainstem: the role of corticosteroids.

The present study examined the effects of repeated administration to rats of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") on 5-hydroxytryptamine1A (5-HT1A) receptor density and mRNA expression in the hippocampus, frontal cortex, and brainstem. As expected, 7 days after subacute MDMA administration (20 mg/kg i.p. twice daily for 4 consecutive days) 5-HT content was markedly reduced (-70%) in the hippocampus and the frontal cortex. 5-HT1A receptor density was increased in the frontal cortex by 23% and decreased in the hippocampus and the brainstem by 25%. These changes correlated with an enhanced or diminished 5-HT1A receptor mRNA expression in the three regions studied. To examine the influence of corticosteroids on these changes, adrenalectomized (ADX) rats received the same dosage regimen as above. Adrenalectomy by itself did not modify 5-HT content in the brain regions examined and increased 5-HT1A receptor density in the hippocampus (+20%) but produced no change in the frontal cortex and brainstem. Adrenalectomy also prevented MDMA-induced changes in receptor number in the hippocampus and brainstem but not in the frontal cortex. Dexamethasone (1 mg/kg/day i.p.) administered for 7 consecutive days reversed the effects of adrenalectomy in the hippocampus but not in the frontal cortex. In the brainstem, MDMA no longer reduced 5-HT1A receptor number in ADX rats, but a significant reduction was restored when ADX animals received the glucocorticoid treatment. The present data show that MDMA may affect 5-HT1A receptors in a regionally dependent manner, notably through a drug effect on corticosterone release, which attenuates 5-HT1A receptor gene transcription selectively in the hippocampus.

Adrenal Cortex Hormones↗
PubMed2004

Functional dissociation between serotonergic pathways in dorsal and ventral hippocampus in psychotomimetic drug-induced locomotor hyperactivity and prepulse inhibition in rats.

Altered hippocampal function and brain serotonin activity are implicated in the development and symptoms of schizophrenia. We have previously shown that lesions of the median raphe nucleus, but not the dorsal raphe nucleus, produced a marked enhancement of locomotor hyperactivity induced by phencyclidine and disruption of prepulse inhibition. The dorsal and ventral hippocampus receive serotonin projections predominantly from the median raphe nucleus and dorsal raphe nucleus, respectively. Therefore, we investigated the effect of local lesions of serotonin projections into the dorsal and ventral hippocampus on psychotomimetic drug-induced locomotor hyperactivity and prepulse inhibition. Male Sprague-Dawley rats were anaesthetized with pentobarbitone and stereotaxically microinjected with 5 microg of the serotonergic neurotoxin 5,7-dihydroxytryptamine into either the dorsal or the ventral hippocampus. Two weeks after surgery, dorsal hippocampus-lesioned rats showed a 100% enhancement of the locomotor hyperactivity caused by phencyclidine treatment and a slight but significant reduction of the effect of amphetamine. Prepulse inhibition was significantly disrupted in lesioned rats and serotonin levels in the dorsal hippocampus were reduced by 80%. Rats with lesions of the ventral hippocampus showed 85% depletion of serotonin and partial disruption of prepulse inhibition, but no significant changes in the effect of phencyclidine or amphetamine. These results suggest that serotonin projections from the median raphe nucleus to the dorsal hippocampus play an important role in locomotor hyperactivity and prepulse inhibition in rats, animal models of aspects of schizophrenia. This suggests that these serotonin projections may be involved in the pathophysiology of schizophrenia symptomology.

Amphetamine↗
PubMed1996

Functional characterization of 5-HT1D autoreceptors on the modulation of 5-HT release in guinea-pig mesencephalic raphe, hippocampus and frontal cortex.

1. The aims of the present study were (i) to characterize further the pharmacology of 5-HT1D autoreceptors modulating 5-HT release in guinea-pig mesencephalic raphe, hippocampus and frontal cortex; (ii) to determine whether 5-HT1D receptors in the mesencephalic raphe are located on 5-HT neurones; (iii) to determine whether 5-HT1D autoreceptors are coupled to G proteins; and (iv) to assess their sensitivity following long-term 5-HT reuptake blockade and inhibition of type-A monoamine oxidase. 2. In mesencephalic raphe, hippocampus and frontal cortex slices, the 5-HT1D/1B receptor agonist, sumatriptan and the 5-HT1 receptor agonist, 5-methoxytryptamine (5-MeOT) but not the 5-HT1B receptor agonist, CP93129, inhibited electrically the evoked release of [3H]-5-HT in a concentration-dependent manner. This effect was antagonized by the 5-HT1D/1B receptor antagonist GR127935 in the three structures, but not by the 5-HT1A receptor antagonist, (+)-WAY100635 in mesencephalic raphe slices. These results confirm the presence of functional 5-HT1D autoreceptors controlling 5-HT release within the mesencephalic raphe as well as in terminal regions. 3. The inhibitory effect of sumatriptan on K(+)-evoked release of [3H]-5-HT was not reduced by the addition of the Na+ channel blocker, tetrodotoxin to the superfusion medium, suggesting that these 5-HT1D receptors in the mesencephalic raphe are located on 5-HT neurones and may be considered autoreceptors. 4. The in vitro treatment with the alkylating agent N-ethylmaleimide (NEM) was used to determine whether these 5-HT1D autoreceptors are coupled to G proteins. The inhibitory effect of sumatriptan on electrically evoked release of [3H]-5-HT was attenuated in NEM-pretreated slices from mesencephalic raphe, hippocampus and frontal cortex, indicating that the 5-HT1D autoreceptors activated by sumatriptan are coupled to G proteins in these three structures. Taken together with our previous results, this suggests that, in addition to the 5-HT1D autoreceptor activated by sumatriptan, another subtype of 5-HT autoreceptor is activated by 5-MeOT in the hippocampus. 5. Following a 3-week treatment with the selective 5-HT reuptake inhibitor, paroxetine (10 mg kg-1 day-1) and a 48 h washout period, the electrically evoked release of [3H]-5-HT was enhanced in mesencephalic raphe, hippocampus and frontal cortex slices. There was an attenuation of the capacity of sumatriptan to inhibit the evoked release of [3H]-5-HT from mesencephalic raphe slices but not from frontal cortex and hippocampus slices. Only in the latter structure was the suppressant effect of 5-MeOT attenuated. After a 3-week treatment with the reversible type-A monoamine oxidase inhibitor, befloxatone (0.75 mg kg-1 day-1) and 48 h washout period, the effectiveness of sumatriptan and 5-MeOT on the evoked release of [3H]-5-HT was unaltered in the same brain structures. 6. The enhancement of [3H]-5-HT release by long-term paroxetine treatment is possibly due to a desensitization of 5-HT1D autoreceptors activated by sumatriptan in mesencephalic raphe and by terminal 5-HT autoreceptors activated by 5-MeOT in hippocampus. In the case of the frontal cortex, it appears that 5-MeOT and sumatriptan may act on the same 5-HT1D autoreceptor which is not desensitized either after paroxetine or befloxatone treatment, as previously reported.

Animals↗
PubMed2003

Systemic hypoxia and the depression of synaptic transmission in rat hippocampus after carotid artery occlusion.

The relationship between step reductions in inspired oxygen and the amplitude of evoked field excitatory postsynaptic potentials (fEPSPs) recorded from hippocampal CA1 neurons was examined in anaesthetized rats with a unilateral common carotid artery occlusion. The amplitudes of fEPSPs recorded from the hippocampus ipsilateral to the occlusion were significantly more depressed with hypoxia than were the fEPSPs recorded from the contralateral hippocampus. The adenosine A1-selective antagonist, 8-cyclopentyl-1,3-dimethylxanthine (8-CPT), blunted the hypoxic depression of the fEPSP. Tissue partial pressure of oxygen (Ptiss,O2) was measured in the ipsilateral and contralateral hippocampus using glass Clark-style microelectrodes. Ptiss,O2 fell to similar levels as a function of inspired oxygen in the ipsilateral and contralateral hippocampus, and in the ipsilateral hippocampus after administration of 8-CPT. Hippocampal blood flow (HBF) was measured using laser Doppler flowmetry. A decline in HBF was associated with systemic hypoxia in both hippocampi. HBF, as a function of inspired oxygen, fell significantly more in the ipsilateral than in the contralateral hippocampus. We conclude that endogenous adenosine acting at the neuronal A1 receptor plays a major role in the depression of synaptic transmission during hypoxic ischaemia. The greater susceptibility of the fEPSP in the ipsilateral hippocampus to systemic hypoxia cannot be explained entirely by differences in Ptiss,O2 or HBF between the two hemispheres.

Adenosine↗
PubMed1998

Functional differentiation along the anterior-posterior axis of the hippocampus in monkeys.

We tested whether the primate hippocampus was functionally heterogenous along its anterior-posterior axis. Two monkeys were trained on both a spatial and nonspatial memory task and the incidence of spatial and nonspatial delay activity in the anterior, middle, and posterior hippocampus was noted. Spatial delay activity (activity in the delay period after the sample stimulus on the spatial memory task) was more common in the posterior than the anterior hippocampus, whereas nonspatial delay activity (activity in the delay period after the sample stimulus on the nonspatial memory task) was evenly distributed throughout the hippocampus. Furthermore, delay neurons in the anterior hippocampus exhibited scalloping delay activity, whereas those in the middle and posterior hippocampus did not. These findings suggest that the hippocampus is functionally heterogeneous and that the posterior regions may be more important for processing spatial information, whereas the anterior regions may be more important for directing or coding movements to points in space.

Acoustic Stimulation↗
PubMed2004

Mineralo- and glucocorticoid receptor mrnas are differently regulated by corticosterone in the rat hippocampus and anterior pituitary.

In most cell lines and animal tissues, glucocorticoid receptors undergo downregulation after exposure to corticosterone. However, corticosterone treatment has not shown a consistent effect on mineralocorticoid (MR) and glucocorticoid receptors (GR) in the hippocampus, and it has been rarely assessed in the anterior pituitary. In this study we investigated dose-dependent effects of corticosterone on MR and GR mRNAs in the hippocampus and anterior pituitary. Adrenalectomized rats substituted with corticosterone in drinking fluid were injected subcutaneously with vehicle or 1, 10, 50, 100, or 200 mg of corticosterone, and sacrificed 4 h later. In the hippocampus we found a progressive decrease in MR and GR mRNAs with increasing doses of corticosterone. This was significant with 50 and 100 mg corticosterone for MR mRNA and with 10-200 mg corticosterone for GR mRNA at plasma corticosterone levels above 30 microg/dl. The anterior pituitary did not show significant changes at any dose. A time-course with 2 mg of corticosterone (non-response dose range at 4 h) revealed a significant decrease in MR and GR mRNAs in the hippocampus 8 h after the subcutaneous injection. In the anterior pituitary both mRNAs showed an increase that was significant 24 h after injection for MR and from 8 to 24 h for GR. In the hippocampus, adrenalectomy (absence of corticosterone) induced a significant increase in MR and GR mRNAs on day 3, but not on days 1, 8 and 21 after adrenalectomy. In the anterior pituitary there were no significant changes at any time after adrenalectomy. In summary, we have found an in vivo corticosterone dose- and time-dependent downregulation of MR and GR mRNAs in the hippocampus, whereas anterior pituitary MRs and GRs seem relatively insensitive to the excess or the absence of corticosterone, suggesting the lack of an autoregulatory effect in this tissue. Significant mRNA changes appearing later in time could suggest a secondary response via a glucocorticoid-induced gene product. Corticosteroid receptor downregulation in the hippocampus could prevent overstimulation or tissue damage when plasma corticosterone is high, while increased corticosteroid receptors in the anterior pituitary could buffer the excessive brain drive on the pituitary during chronic stress or pathological conditions associated with increased plasma glucocorticoids, such as depression.

Animals↗
PubMed1999

MRI volumes of the hippocampus and amygdala in adults with Down's syndrome with and without dementia.

OBJECTIVE: This study sought to determine whether volumes of the hippocampus and amygdala are disproportionately smaller in subjects with Down's syndrome than in normal comparison subjects and whether volume reduction is greater in Down's syndrome subjects with dementia. METHOD: The subjects were 25 adults with Down's syndrome (eight with dementia) and 25 cognitively normal adults who were individually matched on age, sex, and race. Magnetic resonance imaging measures included volumes of the hippocampus, amygdala, and total brain. Nineteen of the Down's syndrome subjects had follow-up scans (interscan interval = 9-41 months). RESULTS: Nondemented Down's syndrome subjects had significantly smaller volumes of the hippocampus, but not the amygdala, than their comparison subjects, even when total brain volume was controlled for. Volumes of both the hippocampus and the amygdala were smaller in the demented Down's syndrome subjects than in their comparison subjects, even when total brain volume was controlled for. Age was not correlated with volume of the hippocampus or amygdala among the nondemented Down's syndrome subjects and the comparison subjects; age was correlated with volume of the amygdala, but not the hippocampus, among the Down's syndrome subjects with dementia. Changes in volume over time were not statistically significant for either the demented or the nondemented subjects. CONCLUSIONS: Hippocampal volume, while disproportionately small for brain size in individuals with Down's syndrome, remains fairly constant through the fifth decade of life in those without dementia. All subjects over age 50 who had Down's syndrome demonstrated volume reduction in the hippocampus as well as clinical signs of dementia. Dementia was also associated with volume reductions in the amygdala that exceeded reductions in total brain volume.

Adult↗
PubMed2002

Estimated neuronal populations and volumes of the hippocampus and its subfields in schizophrenia.

OBJECTIVE: It has been suggested that the primary focus of the pathological process in schizophrenia is on the limbic system, and there have been several postmortem reports of changes in the histological structure or volume of the hippocampus, as well as a larger number of MRI reports of volume reductions. There are conflicting findings, however, with both techniques. METHOD: The authors conducted a study of the gross and subfield structure and cellular composition of the hippocampus in postmortem brains from 30 patients with DSM-IV-diagnosed schizophrenia (13 women, 17 men) and 29 comparison subjects with no psychopathology (14 women, 15 men). Stereological sampling procedures were applied to 25-microm-thick coronal paraffin sections taken at 5-mm intervals throughout the formalin-fixed hippocampus. Subfields were defined as the dentate fascia, the hilus (CA4), an amalgamation of the CA2 and CA3 subfields, the CA1 subfield, and the subiculum. Volumes, cell densities, and cell numbers of the subfields were assessed microscopically, and the volume of the hippocampus was estimated from both photographs and histological slides of the coronal slices. RESULTS: As assessed from histologically stained slides, the volumes of the hippocampus and its subfields did not differ between patients and comparison subjects. Left-sided reduction in hippocampal volumes estimated from photographs, which may have included parahippocampal tissue, was not confirmed on histological examination. No significant differences were observed between patients and comparison subjects in the cellular composition of the hippocampus. CONCLUSIONS: These findings do not support a primary alteration of the hippocampus in schizophrenia.

Aged↗
PubMed2004

Higher atrophy rate of entorhinal cortex than hippocampus in AD.

OBJECTIVES: To determine if atrophy rates were higher for entorhinal cortex (ERC) than for hippocampus in Alzheimer disease (AD), to determine the relationship between hippocampal atrophy rate and memory impairment, and to compare atrophy rates of ERC and hippocampus in differentiating between patients with AD and cognitively normal (CN) controls. METHODS: Twenty patients with AD and 25 CN subjects had MRI scans and clinical evaluations twice approximately 1.9 years apart. ERC volumes were measured manually and hippocampal volumes were measured semiautomatically on volumetric T1-weighted MR images. RESULTS: In AD, the atrophy rate of ERC (7.1 +/- 3.2%/year) was higher (p < 0.02) than that of hippocampus (5.9 +/- 2.4%/year). Furthermore, memory deficit in mild AD, measured with the Delayed List Verbal Recall test, correlated significantly with atrophy rates of both ERC (r = -0.61) and hippocampus (r = -0.59). Atrophy rates of ERC and hippocampus were comparable in differentiating between AD and CN. Using atrophy rates of ERC or hippocampus to detect a 20% treatment effect with 90% power (p < 0.05) would require about 100 completed patients per arm in a 2-year study. CONCLUSION: The finding in AD that the atrophy rate in the entorhinal cortex is higher than in the hippocampus is consistent with the view that AD pathology begins in the entorhinal cortex.

Aged↗
PubMed1999

Amobarbital effects on the posterior hippocampus during the intracarotid amobarbital test.

OBJECTIVE: To relate functional effects on the hippocampus during the intracarotid amobarbital test (IAT) to its direct perfusion with amobarbital. METHODS: In 17 patients with intractable temporal lobe epilepsy, 28 hemispheres were perfused with 2.3 mL of 10% solution of 200 mg amobarbital and 37 MBq 99mTc-hexamethylpropylene amine oxime (HMPAO). For evaluation of amobarbital effects, data were combined from stereo-EEG (S-EEG) recordings from intrahippocampal depth electrodes and high-resolution SPECT after intracarotid injection of HMPAO. RESULTS: Perfusion of the entire hippocampus was observed only in hemispheres with a fetal origin of the posterior cerebral artery (PCA). In 10 hemispheres, S-EEG recordings could not unequivocally be assigned to either the anterior or the posterior part of the hippocampus. In the remaining 18 hemispheres, only the two with a fetal type of PCA showed perfusion of the entire hippocampus. In both, hippocampal electrical activity changed under the influence of amobarbital but did not differ in anterior and posterior contacts. In 15 of 16 hemispheres in which SPECT demonstrated perfusion of the anterior hippocampus only, amobarbital injection resulted in significant S-EEG activity change in both the anterior and the posterior parts of the hippocampus. CONCLUSION: S-EEG effects on the posterior hippocampus during the IAT can occur without direct perfusion of those brain areas.

Adolescent↗