Rat Dentate Gyrus Research Articles

Dendropanax morbifera Léveille extract ameliorates cadmium-induced impairment in memory and hippocampal neurogenesis in rats

BackgroundCadmium leads to learning and memory impairment. Dendropanax morbifera Léveille stem extract (DMS) reduces cadmium-induced oxidative stress in the hippocampus. We investigated the effects of DMS on cadmium-induced impairments in memory in rats.MethodsCadmium (2 mg/kg), with or without DMS (100 mg/kg), was orally administered to 7-week-old Sprague-Dawley rats for 28 days. Galantamine (5 mg/kg), an acetylcholinesterase inhibitor, was intraperitoneally administered as a positive control. A novel-object recognition test was conducted 2 h after the final administration. Cell proliferation and neuroblast differentiation were assessed by immunohistochemistry for Ki67 and doublecortin, respectively. Acetylcholinesterase activity in the synaptosomes of the hippocampus was also measured based on the formation of 5,5′-dithio-bis-acid nitrobenzoic acid.ResultsAn increase in the preferential exploration time of new objects was observed in both vehicle-treated and cadmium-treated rats. In addition, DMS administration increased cell proliferation and neuroblast differentiation in the dentate gyrus of vehicle-treated and cadmium-treated rats. Acetylcholinesterase activity in the hippocampal synaptosomes was also significantly higher in the DMS-treated group than in the vehicle-treated group. The effect of DMS on cadmium-induced memory impairment and cell proliferation in the hippocampus was comparable to that of galantamine.ConclusionsThese results suggest that DMS ameliorates cadmium-induced memory impairment via increase in cell proliferation, neuroblast differentiation, and acetylcholinesterase activity in the hippocampus. The consumption of DMS may reduce cadmium-induced neurotoxicity in animals or humans.

Amyloid β Is Not the Major Factor Accounting for Impaired Adult Hippocampal Neurogenesis in Mice Overexpressing Amyloid Precursor Protein.

SummaryAdult hippocampal neurogenesis was impaired in several Alzheimer's disease models overexpressing mutant human amyloid precursor protein (hAPP). However, the effects of wild-type hAPP on adult neurogenesis and whether the impaired adult hippocampal neurogenesis was caused by amyloid β (Aβ) or APP remained unclear. Here, we found that neurogenesis was impaired in the dentate gyrus (DG) of adult mice overexpressing wild-type hAPP (hAPP-I5) compared with controls. However, the adult hippocampal neurogenesis was more severely impaired in hAPP-I5 than that in hAPP-J20 mice, which express similar levels of hAPP mRNA but much higher levels of Aβ. Furthermore, reducing Aβ levels did not affect the number of doublecortin-positive cells in the DG of hAPP-J20 mice. Our results suggested that hAPP was more likely an important factor inhibiting adult neurogenesis, and Aβ was not the major factor affecting neurogenesis in the adult hippocampus of hAPP mice.

High Pressure and [Ca 2+ ] Produce an Inverse Modulation of Synaptic Input Strength and Network Excitability in the Rat Dentate Gyrus.

Hyperbaric environments induce the high pressure neurological syndrome (HPNS) characterized by hyperexcitability of the central nervous system (CNS) and memory impairment. Human divers and other animals experience the HPNS at pressures beyond 1.1 MPa. High pressure depresses synaptic transmission and alters its dynamics in various animal models. Medial perforant path (MPP) synapses connecting the medial entorhinal cortex with the hippocampal formation are suppressed by 50% at 10.1MPa. Reduction of synaptic inputs is paradoxically associated with enhanced ability of dentate gyrus (DG)’ granule cells (GCs) to generate spikes at high pressure. This mechanism allows MPP inputs to elicit standard GC outputs at 0.1–25 Hz frequencies under hyperbaric conditions. An increased postsynaptic gain of MPP inputs probably allows diving animals to perform in hyperbaric environments, but makes them vulnerable to high intensity/frequency stimuli producing hyperexcitability. Increasing extracellular Ca2+ ([Ca2+]o) partially reverted pressure-mediated depression of MPP inputs and increased MPP’s low-pass filter properties. We postulated that raising [Ca2+]o in addition to increase synaptic inputs may reduce network excitability in the DG potentially improving its function and reducing sensitivity to high intensity and pathologic stimuli. For this matter, we activated the MPP with single and 50 Hz frequency stimuli that simulated physiologic and deleterious conditions, while assessing the GC’s output under various conditions of pressure and [Ca2+]o. Our results reveal that the pressure and [Ca2+]o produce an inverse modulation on synaptic input strength and network excitability. These coincident phenomena suggest a potential general mechanism of networks that adjusts gain as an inverse function of synaptic inputs’ strength. Such mechanism may serve for adaptation to variable pressure and other physiological and pathological conditions and may explain the increased sensitivity to strong sensory stimulation suffered by human deep-divers and cetaceans under hyperbaric conditions.

Effects of Exogenous Estrogen Treatment on Hippocampal Neurogenesis of Diabetic Ovariectomized Rats

Background: Mellitus Diabetes (DM) is the most important metabolic diseases. The incidence of DM is prone to increase. Vasculopathy, retinopathy, central and peripheral neuropathy are the most important reported side effects of DM. Cognitive dysfunction following DM reported in both sexes. Hippocampus is a major part of brain involving in cognitive function, its cells are able to neurogenesis, so it is possible that DM affects the hippocampus. In addition, neuroprotective effects of female sex steroids are reported elsewhere. In order to answer the question of whether female sex steroid are able to suppress the effects of DM on neurogenesis of dentate gyrus (DG) in diabetic ovariectomized rat the present study designed. Methods: Sprague-Dawley adult female rats were used in this study. The animals randomly divided in 8 groups including; control, diabetic (Diab), ovariectomy (OVX), Diab+OVX, estrogen treated (E2; Diab+OVX+E2), surgical and vehicle sham. Intrapritoneal injection of STZ, subcutaneous injection of E2 and routine bilateral surgery were used respectively to induce diabetes, estrogen treatment and OVX. Nissl staining, Brdu immunohistochemistry (IHC) and western blotting were used in this study. Statistical analysis was done and the results presented in mean ± SD, P v < 0.05 considered significant. Results: Brdu IHC showed that the neurogenesis significantly decreased in OVX, Diab and OVX-Diab groups (P v < 0.05) in comparison with control and sham groups. Western blotting showed significant increase of Bax and decrease of Bcl2 proteins of trial groups comparing to control. Estrogen treatment significantly improved neurogenesis in animals of Diab+OVX+E2 group. The neurogenesis impairment was more sever in OVX + Diab animals than OVX and Diab ones merely. Conclusion: Based on our data, cognitive dysfunction caused by DM is related to hippocampal neurogenesis reduction and might improve under the influence of ovarian steroidal hormone therapy.

Chronic corticosterone administration reduces dendritic complexity in mature, but not young granule cells in the rat dentate gyrus

Background: Our previous work has shown that exposure to the stress hormone corticosterone (40 mg/kg CORT) for two weeks induces dendritic atrophy of pyramidal neurons in the hippocampal CA3 region and behavioral deficits. However, it is unclear whether this treatment also affects the dentate gyrus (DG), a subregion of the hippocampus comprising a heterogeneous population of young and mature neurons.Objective: We examined the effect of CORT treatment on the dendritic complexity of mature and young granule cells in the DG.Methods: We utilized a Golgi staining method to investigate the dendritic morphology and spine density of young neurons in the inner granular cell layer (GCL) and mature neurons in the outer GCL in response to CORT application. The expressions of glucocorticoid receptors during neuronal maturation were examined using Western blot analysis in a primary hippocampal neuronal culture.Results: Sholl analysis revealed that CORT treatment decreased the number of intersections and shortened the dendritic length in mature, but not young, granule cells. However, the spine density of mature and young neurons was not affected. Western blot analysis showed a progressive increase in the protein levels of glucocorticoid receptors (GRs) in the cultured primary hippocampal neurons during neuronal maturation.Conclusion: These data suggest that mature neurons are likely more vulnerable to chronic exposure to CORT; this may be due to their higher expression of GRs when compared to younger DG neurons.

Interactive effects of AM251 and baclofen on synaptic plasticity in the rat dentate gyrus

Long-term potentiation (LTP), a form of synaptic plasticity, is considered to be a critical cellular mechanism that underlies learning and memory. Cannabinoid CB1 and metabotropic GABAB receptors display similar pharmacological effects and co-localize in certain brain regions. In this study, we examined the effects of co-administration of the CB1 and GABAB antagonists AM251 and baclofen, respectively, on LTP induction in the rat dentate gyrus (DG).Male Wistar rats were anesthetized with urethane. A stimulating electrode was placed in the lateral perforant path (PP), and a bipolar recording electrode was inserted into the DG until maximal field excitatory postsynaptic potentials (fEPSPs) were observed. LTP was induced in the hippocampal area by high-frequency stimulation (HFS) of the PP. fEPSPs and population spikes (PS) were recorded at 5, 30, and 60min after HFS in order to measure changes in the synaptic responses of DG neurons.Our results showed that HFS coupled with administration of AM251 and baclofen increased both PS amplitude and fEPSP slope. Furthermore, co-administration of AM251 and baclofen elicited greater increases in PS amplitude and fEPSP slope.The results of the present study suggest that CB1 receptor activation in the hippocampus mainly modifies synapses onto GABAergic interneurons located in the DG. Our results further suggest that, when AM251 and baclofen are administered simultaneously, AM251 can alter GABA release and thereby augment LTP through GABAB receptors. These results suggest that functional crosstalk between cannabinoid and GABA receptors regulates hippocampal synaptic plasticity.

Sensorimotor Intervention Recovers Noradrenaline Content in the Dentate Gyrus of Cortical Injured Rats.

Nowadays, a consensus has been reached that designates the functional and structural reorganization of synapses as the primary mechanisms underlying the process of recovery from brain injury. We have reported that pontine noradrenaline (NA) is increased in animals after cortical ablation (CA). The aim of the present study was to explore the noradrenergic and morphological response after sensorimotor intervention (SMI) in rats injured in the motor cortex. We used male Wistar adult rats allocated in four conditions: sham-operated, injured by cortical ablation, sham-operated with SMI and injured by cortical ablation with SMI. Motor and somatosensory performance was evaluated prior to and 20 days after surgery. During the intervening period, a 15-session, SMI program was implemented. Subsequently, total NA analysis in the pons and dentate gyrus (DG) was performed. All groups underwent histological analysis. Our results showed that NA content in the DG was reduced in the injured group versus control, and this reduction was reverted in the injured group that underwent SMI. Moreover, injured rats showed reduction in the number of granule cells in the DG and decreased dentate granule cell layer thickness. Notably, after SMI, the loss of granule cells was reverted. Locus coeruleus showed turgid cells in the injured rats. These results suggest that SMI elicits biochemical and structural modifications in the hippocampus that could reorganize the system and lead the recovery process, modulating structural and functional plasticity.

Sodium Butyrate, a Histone Deacetylase Inhibitor, Exhibits Neuroprotective/Neurogenic Effects in a Rat Model of Neonatal Hypoxia-Ischemia

Neonatal hypoxic-ischemic (HI) injury still remains an important issue as it is a major cause of neonatal death and neurological dysfunctions. Currently, there are no well-established treatments to reduce brain damage and its long-term sequel in infants. Recently, reported data show that histone deacetylase inhibitors provide neuroprotection in adult stroke models. However, the proof of their relevance in vivo after neonatal HI brain injury remains particularly limited. In the present study, we show neuroprotective/neurogenic effect of sodium butyrate (SB), one of histone deacetylase inhibitors (HDACis), in the dentate gyrus of HI-injured immature rats. Postnatal day 7 (P7) rats underwent left carotid artery ligation followed by 7.6 % O2 exposure for 1 h. SB (300 mg/kg) was administered in a 5-day regime with the first injection given immediately after the onset of HI. The damage of the ipsilateral hemisphere was evaluated by weight deficit. Newly produced cells were labeled with BrdU, at 50 mg/kg, injected twice daily for 3 consecutive days. Subsequent differentiation of the newborn cells was investigated 2 and 4 weeks after the insult by immunohistochemistry using neuronal and glial cell-lineage markers and BrdU incorporation. Finally, we performed several behavioral tests to evaluate functional outcome. In summary, SB led to a remarkable reduction of the brain damage caused by HI. Moreover, the application of this HDACi protected against HI-induced loss of neuroblasts and oligodendrocyte precursor cells, as well as against neuroinflammation. The observed neuroprotective action suggests that SB may serve as a potential candidate for future treatment of HI-evoked injury in neonates.

Enriched environment ameliorates depression-induced cognitive deficits and restores abnormal hippocampal synaptic plasticity

Severe depression compromises structural and functional integrity of the brain and results in impaired learning and memory, maladaptive synaptic plasticity as well as degenerative changes in the hippocampus and amygdala. The precise mechanisms underlying cognitive dysfunctions in depression remain largely unknown. On the other hand, enriched environment (EE) offers beneficial effects on cognitive functions, synaptic plasticity in the hippocampus. However, the effect of EE on endogenous depression associated cognitive dysfunction has not been explored. Accordingly, we have attempted to address this issue by investigating behavioural, structural and synaptic plasticity mechanisms in an animal model of endogenous depression after exposure to enriched environment. Our results demonstrate that depression is associated with impaired spatial learning and enhanced anxiety-like behaviour which is correlated with hypotrophy of the dentate gyrus and amygdalar hypertrophy. We also observed a gross reduction in the hippocampal long-term potentiation (LTP). We report a complete behavioural recovery with reduced indices of anhedonia and behavioural despair, reduced anxiety-like behaviour and improved spatial learning along with a complete restoration of dentate gyrus and amygdalar volumes in depressive rats subjected to EE. Enrichment also facilitated CA3-Schaffer collateral LTP. Our study convincingly proves that depression-induces learning deficits and impairs hippocampal synaptic plasticity. It also highlights the role of environmental stimuli in restoring depression-induced cognitive deficits which might prove vital in outlining more effective strategies to treat major depressive disorders.

NMDA receptor antagonist prevents cell death in the hippocampal dentate gyrus induced by hyponatremia accompanying adrenal insufficiency in rats

Selective apoptosis of granule cells in the hippocampal dentate gyrus (DG) of rats with bilateral adrenalectomy (ADX) and in patients who died of adrenal insufficiency has been reported. Although adrenal insufficiency is a common disease and is usually associated with hyponatremia, its effect on the central nervous system and in apoptosis in the hippocampus remain to be elucidated. Using rat models to represent clinical hyponatremia accompanying adrenal insufficiency, we show that reduced serum [Na+] was associated with selective apoptosis in the DG. Nine days after ADX, apoptotic cells were observed in the DG of rats whose serum [Na+] was <125mEq/L (moderate hyponatremia), but rarely in those whose serum [Na+] was ≥125mEq/L or in normonatremic rats. Although all hyponatremic ADX rats survived following treatment with corticosterone and saline started 7days after ADX when apoptosis had not yet occurred, selective apoptosis on day 9 was not prevented in moderately hyponatremic rats. Interestingly, treatment with memantine, a noncompetitive NMDAR antagonist, prevented the selective apoptosis in the DG in moderately hyponatremic, ADX rats, and improved electrophysiological dysfunction, including impaired basal synaptic transmission and long-term potentiation at the entorhinal cortex-DG synapses. These results demonstrated that in adrenal insufficient rats, hyponatremia was associated with apoptosis in the DG, and that memantine prevented the apoptosis and improved cell function. Our data imply the importance of assessing the possibility of neurological impairments after treatment with CORT in patients with moderate or severe hyponatremia accompanying adrenal insufficiency and that memantine may represent a beneficial therapeutic strategy to prevent neurological impairments in such patients.

Place field detection using grid-based clustering in a large-scale computational model of the rat dentate gyrus.

Place cells are neurons in the hippocampus that are sensitive to location within an environment. Simulations of a large-scale, computational model of the rat dentate gyrus using grid cell input have been performed resulting in granule cells that express multiple place fields. The typical method of detecting place fields using a global threshold on this data is unreliable as the characteristics of the place fields from a single neuron can be highly variable. A grid-based implementation of DENCLUE has been developed to calculate local thresholds to identify each place field. An adaptive binning algorithm used to smooth the rate maps was combined with the DENCLUE implementation to adaptively choose the size of the smoothing kernel and reduce the number of free parameters of the total algorithm. A sensitivity analysis was performed using the threshold parameter to demonstrate the robustness of using local thresholds as opposed to using a single global threshold in detecting the place fields resulting from the large-scale simulation. The analysis supports the use of applying local thresholds for place field detection and will be used to further investigate the role of granule cells in hippocampal function.

Effects of lentiviral delivery in different brain regions on transfection of rat dentate gyrus neurons

Objective To explore the effect of lentiviral delivery green fluorescent protein in different brain regions on the transfection of dentate gyrus neurons. Methods Lenti-pSyn-EGFP was stereotaxic injected into dentate gyrus (DG), Cornu Ammonis 1 (CA1) of hippocampus and medial entorhinal cortex (EC) of rats. All animals were perfused with 4% paraformaldehyde. Their brains were cut into 30 μm sections which were performed with Nissl fluorescent staining. Results The resuts showed that the GFP positive cells in DG area of DG, CA1, EC, DG-EC groups were (18.0±1.0), (17.0±0.6), (17.3±0.6), (18.3±0.6) respectively, and there was no statistical difference among each group(P>0.05). Conclusion Lentivirus delivery in EC and CA1 both can transfect DG neurons. This is a useful method to transfect dentate gyrus neurons instead of injecting lentivirus into DG directly and avoid the lesion of DG. Key words: Lentivirus; Dentate gyrus; Hippocampus; Medial entorhinal cortex

Selective plasticity of hippocampal GABAergic interneuron populations following kindling of different brain regions.

The vulnerability and plasticity of hippocampal GABAergic interneurons is a topic of broad interest and debate in the field of epilepsy. In this experiment, we used the electrical kindling model of epilepsy to determine whether seizures that originate in different brain regions have differential effects on hippocampal interneuron subpopulations. Long-Evans rats received 99 electrical stimulations of the hippocampus, amygdala, or caudate nucleus, followed by sacrifice and immunohistochemical or western blot analyses. We analyzed markers of dendritic (somatostatin), perisomatic (parvalbumin), and interneuron-selective (calretinin) inhibition, as well as an overall indicator (GAD67) of interneuron distribution across all major hippocampal subfields. Our results indicate that kindling produces selective effects on the number and morphology of different functional classes of GABAergic interneurons. In particular, limbic kindling appears to enhance dendritic inhibition, indicated by a greater number of somatostatin-immunoreactive (-ir) cells in the CA1 pyramidal layer and robust morphological sprouting in the dentate gyrus. We also found a reduction in the number of interneuron-selective calretinin-ir cells in the dentate gyrus of hippocampal-kindled rats, which suggests a possible reduction of synchronized dendritic inhibition. In contrast, perisomatic inhibition indicated by parvalbumin immunoreactivity appears to be largely resilient to the effects of kindling. Finally, we found a significant induction in the number of GAD67-cells in caudate-kindled rats in the dentate gyrus and CA3 hippocampal subfields. Taken together, our results demonstrate that kindling has subfield-selective effects on the different functional classes of hippocampal GABAergic interneurons. J. Comp. Neurol. 525:389-406, 2017. © 2016 Wiley Periodicals, Inc.

Increased protein expression levels of pCREB, BDNF and SDF-1/CXCR4 in the hippocampus may be associated with enhanced neurogenesis induced by environmental enrichment.

Brain plasticity is very sensitive to the environment. Certain neurotrophic factors and neurotransmitter receptors, including brain-derived neurotrophic factor (BDNF), cyclic adenosine monophosphate response element‑binding protein (CREB), stromal cell‑derived factor‑1 (SDF‑1) and its specific receptor, C-X-C motif chemokine receptor 4 (CXCR4), are important in neurogenesis in adult animals. In the present study, the effects of environmental enrichment (EE) on neurogenesis in the dentate gyrus (DG) and subventricular zone (SVZ), and the protein expression levels of BDNF, CREB, SDF‑1 and CXCR4 were investigated. Adult rats were randomly assigned as controls or underwent EE for 30days. Subsequently, immunofluorescence staining was used to analyze cell proliferation in the DG and SVZ, and the differentiation and survival of newly‑formed cells in the hippocampus. The protein expression levels of BDNF, phosphorylated CREB (pCREB), protein kinase A catalytic subunit α, SDF‑1 and CXCR4 in the hippocampus were assayed by western blotting. Cognitive function was assessed in a Morris water maze. EE improved cognitive function, and increased the proliferation, differentiation and survival of newly‑formed neurons in the DG of adult rats; however, EE did not activate neurogenesis in the SVZ. Furthermore, EE enhanced the protein expression levels of BDNF, pCREB, SDF-1 and CXCR4 in the hippocampus. These results provide a theoretical basis to explain the beneficial effects of EE on healthy, adult rats.

Plasminogen Activator Inhibitor-1 in depression: Results from Animal and Clinical Studies.

Evidence suggests that plasminogen activator inhibitor-1 (PAI-1) is a stress-related factor, and serum PAI-1 levels are increased in patients with major depressive disorders (MDD). Herein, we analysed PAI-1 protein levels in the brain, cerebrospinal fluid (CSF) and serum of rodents exposed to chronic unpredictable mild stress or treated with escitalopram. In addition, we examined PAI-1 concentrations in serum obtained from 17 drug-free depressed patients before and after escitalopram treatment. We found that PAI-1 expression was increased in area 1 of the cingulate cortex and prelimbic cortex of the medial prefrontal cortex as well as in the hippocampal cornu ammonis 3 and dentate gyrus in stressed rats. A downregulation of PAI-1 following chronic escitalopram treatment was also found. PAI-1 levels were higher in the CSF and serum in stressed rats than in controls, although the difference did not reach statistical significance in the serum. Escitalopram treatment significantly decreased PAI-1 levels in the serum, but not in the CSF. MDD patients had significantly greater serum PAI-1 concentrations than controls. Our results suggest that PAI-1 is implicated in the pathophysiology of depression.

ISX-9 can potentiate cell proliferation and neuronal commitment in the rat dentate gyrus

Adult hippocampal neurogenesis can be modulated by various physiological and pathological conditions, including stress, affective disorders, and several neurological conditions. Given the proposed role of this form of structural plasticity in the functioning of the hippocampus (namely learning and memory and affective behaviors), it is believed that alterations in hippocampal neurogenesis might underlie some of the behavioral deficits associated with these psychiatric and neurological conditions. Thus, the search for compounds that can reverse these deficits with minimal side effects has become a recognized priority. In the present study we tested the pro-neurogenic effects of isoxazole 9 (Isx-9), a small synthetic molecule that has been recently identified through the screening of chemical libraries in stem cell-based assays. We found that administration of Isx-9 for 14days was able to potentiate cell proliferation and increase the number of immature neurons in the hippocampal DG of adult rats. In addition, Isx-9 treatment was able to completely reverse the marked reduction in these initial stages of the neurogenic process observed in vehicle-treated animals (which were submitted to repeated handling and exposure to daily intraperitoneal injections). Based on these results, we recommend that future neurogenesis studies that require repeated handling and manipulation of animals should include a naïve (non-manipulated) control to determine the baseline levels of hippocampal cell proliferation and neuronal differentiation. Overall, these findings demonstrate that Isx-9 is a promising synthetic compound for the mitigation of stress-induced deficits in adult hippocampal neurogenesis. Future studies are thus warranted to evaluate the pro-neurogenic properties of Isx-9 in animal models of affective and neurological disorders associated with impaired hippocampal structural plasticity.

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The expression of a highly polysialylated form of the neural cell adhesion molecule (NCAM-H), often termed ‘embryonic NCAM’, has been investigated in the hippocampal formation of developing and adult rats. To determine the immunohistochemical localization of NCAM-H, a monoclonal antibody that reacts with the polysialic acid portion of NCAM-H was used. In the late embryonic and early postnatal periods, immunoreactivity for NCAM-H was found throughout the hippocampal formation, except for the ventricular layer. Thereafter, the immunoreactivity gradually decreased and almost vanished in most parts in the adult. However, a strong immunoreactivity remained on a number of cells in the dentate gyrus of adult rats, particularly in the deepest part of the granular layer. The immunoreaclive arborized dendrites, mostly arising from the primary apical pole of the granule cells, were found to enter the molecular layer. The mossy fibers also were positive. Electron-microscopic examination of the hilus portion showed that the immunoreactivity was detected on the plasma membrane of some axons in the mossy fiber bundles. Since postnatal,neurogenesis is known to continue into adulthood in the deepest part of the granule cell layer of the dentate gyrus, these results suggest that, in the adult dentate gyrus, NCAM-H is expressed by newly generated granule cells, and that the NCAM-H-expressing new cells may participate in the formation of new neural circuits.

Daily access to sucrose impairs aspects of spatial memory tasks reliant on pattern separation and neural proliferation in rats.

High sugar diets reduce hippocampal neurogenesis, which is required for minimizing interference between memories, a process that involves “pattern separation.” We provided rats with 2 h daily access to a sucrose solution for 28 d and assessed their performance on a spatial memory task. Sucrose consuming rats discriminated between objects in novel and familiar locations when there was a large spatial separation between the objects, but not when the separation was smaller. Neuroproliferation markers in the dentate gyrus of the sucrose-consuming rats were reduced relative to controls. Thus, sucrose consumption impaired aspects of spatial memory and reduced hippocampal neuroproliferation.

Effect of Audiogenic Seizures on the Dynamics of Fatty Acid Composition of Hippocampal Dental Gyrus in Krushinsky-Molodkina Rats

Changes in the fatty acid composition of the hippocampal dentate gyrus in Krushinsky-Molodkina rats with hereditary predisposition to audiogenic seizures were studied in 1, 3, and 14 days after 1 or 5 seizures. Seizure activity changed the content of saturated and monounsaturated as well as polyunsaturated fatty acids at different terms after seizures. After seizures, the content of individual fatty acids changed in different directions. Similar shifts after 1 and 5 seizures were observed only for eicosapentaenoic acid at all observation terms. More pronounced changes in fatty acid composition were observed after 5 seizures. These results can be useful for the development of new approaches to correction of seizure activity.

Combined immunohistochemical and retrograde tracing reveals little evidence of innervation of the rat dentate gyrus by midbrain dopamine neurons

Although the functional neuroanatomy of the midbrain dopamine (mDA) system has been well characterized, the literature regarding its capacity to innervate the hippocampal formation has been inconsistent. The lack of expression of definitive markers for dopaminergic fibers, such as the dopamine transporter, in the hippocampus has complicated studies in this area. Here we have used immunohistochemical techniques to characterize the tyrosine hydroxylase expressing fiber network in the rat hippocampus, combined with retrograde tracing from the dentate gyrus to assess the capacity for afferent innervation by mDA neurons. The results indicate that virtually all tyrosine hydroxylase fibers throughout the hippocampus are of a noradrenergic phenotype, while the overlying cortex contains both dopaminergic and noradrenergic fiber networks. Furthermore, retrograde tracing from the dentate gyrus robustly labels tyrosine hydroxylase-immunoreactive noradrenergic neurons in the locus coeruleus but not mDA neurons.