[Comparison of the application methods and effects of skin flaps in the repair of defects in different parts of the nose according to the concept of aesthetic nosesubunits].

Objective: To analyze the difference of application methods and effects of local flap in small and medium-sized defects of different aesthetic subunits of nose, in order to provide reference for clinical work. Methods: A retrospective analysis was made on 59 patients with external nasal masses and scars who underwent surgical treatment in the Department of Aesthetic Plastic Surgery of the Affiliated Hospital of Qingdao University from July 1, 2021 to January 30, 2022, including 27 females and 32 males, aged 15 to 69 years. Using Likert scale, the repair methods and effects of local flap for nasal soft tissue defects were evaluated and summarized from three aspects of texture, flatness and scar concealment. GraphPad Prism 5.0 software was used for data statistics and analysis. Results: The use of skin flaps to repair small and medium-sized areas of the nose could achieve satisfactory results. For patients with different subunits, in terms of skin flatness and scar concealment degree in the operation area, patients' satisfaction with the dorsal and lateral nasal areas was higher than that of the alar and tip areas, respectively (F=6.40, P=0.001; F=10.57, P<0.001). For patients with different skin flap repair methods, the satisfaction of patients with Z-plasty and Dufourmentel skin flap was higher than that of other skin flap repair methods (F=4.38, P=0.002), and the satisfaction of patients with Dufourmentel skin flap was the highest in the degree of scar concealment (F=2.57, P=0.038). Conclusions: In the small and medium-sized defects of the nose, the use of multiple local flaps can achieve good cosmetic effects and functional recovery. The operator should select the appropriate flap repair method according to the characteristics of different aesthetic subunits of the nose.

[Study on the relationship between quality of nursing professional life and depression tendency of nursing staff].

Objective: To explore the relationship between the quality of professional life and depression tendency of nurses. Methods: From November 2018 to January 2019, 242 nurses from some third-class A hospitals were randomly selected as the subjects. The Quality of Professional Life Scale of Nurses were used to evaluate the status of nurses' professional life quality, and the depression state of nurses was measured by Self Rating Depression Scale, and the relationship between them was analyzed. Results: The total score of professional life of nurses was (156.86±26.60) , including family work balance (24.60±4.73) , working environment (77.30±14.78) , workload (36.34±6.11) and social environment (18.62±4.21) . The total score of depression tendency of nurses was (43.76±9.50) , the overall depression tendency rate was 64.46% (156/242) , and the incidence rates of moderate and severe depression tendency were 23.55% (57/242) and 10.74% (26/242) , respectively. There was negative correlation between the total score of professional quality of life and each dimension score with depression tendency (P<0.05) ; Multiple linear regression analysis showed that high quality of professional life was the protective factor of depression tendency of nurses (P<0.001) . Conclusion: The quality of professional life of nurses is related to depression tendency, and the high quality of professional life is not prone to depression.

Dissecting the role of Krüppel homolog 1 in the metamorphosis and female reproduction of the cotton bollworm, Helicoverpa armigera.

In insects, metamorphosis and reproduction are controlled by juvenile hormone (JH) and 20-hydroxyecdysone (20E). Krüppel homolog 1 (Kr-h1), a transcription factor, is regarded as a JH-early inducible gene responsible for the repression of metamorphosis. However, the role of Kr-h1 in reproduction of holometabolic insects is relatively less understood. In this study, we studied the role of Kr-h1 in larvae-pupae transition and female reproduction in the major agricultural pest Helicoverpa armigera. Two HaKr-h1 isoforms (HaKr-h1α and HaKr-h1ß) were identified, with HaKr-h1α predominant in the cotton bollworm. In larvae, HaKr-h1 was predominately expressed in the epidermis and markedly up-regulated during the moult stage, whereas in adults HaKr-h1 was mainly expressed in females and the highest transcription was detected in the ovaries. Considering the function of hormones in larval metamorphosis, we examined the modulation of gene expression in response to hormones, which showed that HaKr-h1 was significantly induced by both JH analogue (JHA) and 20E. Knockdown of HaKr-h1 in fifth-instar larvae resulted in precocious metamorphosis from larvae to pupae. Moreover, a fluorescence immunoassay coupled with heterologous expression revealed that HaKr-h1 was localized in the nucleus of oocyte membrane. In female adults, depletion of HaKr-h1 severely repressed the transcription of vitellogenin, disrupted oocyte maturation and reduced the number of eggs laid, suggesting that HaKr-h1 is required for vitellogenesis and egg production in H. armigera. The present study provides insight into the roles of HaKr-h1 in JH-mediated reproduction and highlights HaKr-h1 as a target for suppression of lepidopteran pests.

Reproductive Cost Associated With Juvenile Hormone in Bt-Resistant Strains of Helicoverpa armigera (Lepidoptera: Noctuidae).

Transgenic Bacillus thuringiensis (Bt) crops are increasingly significant in pest control, but resistance development of target pests is a major issue in the sustainable deployment of Bt crops. The fitness cost of resistance in target pests is regarded as one of the main factors delaying resistance when adopting the refuge strategy. In this study, we compared the life-history traits of three independent sets of Helicoverpa armigera (Hübner, 1809) adults, of each there were a susceptible population and a Cry1Ac-resistant population derived by selection from it. Confirming to the previous studies, resistant individuals exhibited fewer progeny, less fecundity, lower egg hatching rate, and longer adult longevity. And poor fecundity in resistant strains was associated with the decline of the mature follicular amount, the ovarian weight ratio, and the length of the longest ovarian tubule. Interestingly, the juvenile hormone (JH) level appeared higher in resistant strains relative to susceptible strains. Application of methoprene (JH analogue) in vivo was effective in reducing fecundity and hatchability with the up-regulation of detected JH titer. These results suggested that resistance against Bt toxin reduced the reproductive capacity of H. armigera, and JH level is affected in the tradeoff between reproductive capacity and Bt resistance.

Intestinal lactic acid bacteria from Muscovy duck as potential probiotics that alter adhesion factor gene expression.

The purpose of this study was to assess the suitability of lactic acid bacteria (LABs) isolated from Muscovy duck as a potential probiotic. Isolates were identified by targeted polymerase chain reaction and assessed in vitro for probiotic characteristics such as autoaggregation; surface-charge; hydrophobicity; tolerance to acidic pH, bile salts and protease; and expression of genes involved in Caco-2 cell adhesion. The LAB isolates exhibited strong resistance to high bile concentration and acidic pH, produced lactic acid, and bacteriostatic (P < 0.05) were identified as bacilli compared with LAB isolates of cocci. Additionally, the LAB isolates showed high sensitivity to penicillin and tetracycline antibiotics, while they were resistant to ofloxacin, Macrodantin, and cotrimoxazole. The level of F-actin mRNA increased in the groups treated with CM3, Salmonella enterica, and CM3 + S. enterica (P < 0.0001, P < 0.05 and P < 0.05 ). The level of cell adhesion molecule (CAM) and E-cadherin (E-cad) mRNA expression was significantly lower in the treatment group (P < 0.05 for both) than in the control. The F-actin, CAM, and E-cad mRNA levels were significantly lower in the S. enterica and CM3 + S. enterica groups (P < 0.01) than in the CM3 group. Among these, RNA levels were higher in the CM3 + S. enterica than S. enterica group. These results indicate that the natural duck gut microflora is an excellent source for probiotic bacteria and can facilitate the establishment of criteria to select probiotic strains for the prevention of diarrhea.

A clinical study of pingyangmycin sclerotherapy for venous malformation: an evaluation of 281 consecutive patients.

WHAT IS KNOWN AND OBJECTIVE: In China, lidocaine together with 2 mg/mL of pingyangmycin (PYM, also known as bleomycin A5) is recommended for the treatment of venous malformations (VMs). The purpose of this study was to investigate whether lidocaine has a synergistic effect with PYM in improving the therapeutic outcomes of patients with VMs. Additionally, this study aimed to evaluate the outcomes of sclerotherapy for VMs using an intralesional injection of a low concentration of PYM (0·5 mg/mL). METHODS: A total of 281 patients with VMs were treated with 0·5 or 2 mg/mL of PYM with or without lidocaine and dexamethasone (DEX). All of the patients received a direct intralesional injection at a rate of 1 mL/min, and the volume of the solution varied from 1·5 to 6·0 mL per injection. RESULTS AND DISCUSSION: No significant differences were observed in the clinical outcomes between the PYM and PYM + lidocaine treatment groups (P > 0·05). The clinical outcomes were similar between the groups that were treated with 0·5 and 2 mg/mL of PYM, but the swelling and pain in the patients who were treated with 0·5 mg/mL of PYM were less severe compared with the patients who were treated with 2 mg/mL of PYM. A total of 29 patients with VM lesions on the glans penis were treated with 0·5 mg/mL of PYM + 0·5% lidocaine. Of these patients, 26 were cured, whereas three experienced a marked improvement. WHAT IS NEW AND CONCLUSION: Lidocaine does not have a synergistic effect with PYM in improving the therapeutic outcomes of patients with VMs. Sclerotherapy with a low concentration of PYM (0·5 mg/mL) combined with lidocaine and DEX is a safe and effective therapy for small superficial VMs of critical organs, such as the lips and the glans penis.

Depletion of pre-mRNA splicing factor Cdc5L inhibits mitotic progression and triggers mitotic catastrophe.

Disturbing mitotic progression via targeted anti-mitotic therapy is an attractive strategy for cancer treatment. Therefore, the exploration and elucidation of molecular targets and pathways in mitosis are critical for the development of anti-mitotic drugs. Here, we show that cell division cycle 5-like (Cdc5L), a pre-mRNA splicing factor, is a regulator of mitotic progression. Depletion of Cdc5L causes dramatic mitotic arrest, chromosome misalignments and sustained activation of spindle assembly checkpoint, eventually leading to mitotic catastrophe. Moreover, these defects result from severe impairment of kinetochore-microtubule attachment and serious DNA damage. Genome-wide gene expression analysis reveals that Cdc5L modulates the expression of a set of genes involved in the mitosis and the DNA damage response. We further found that the pre-mRNA splicing efficiency of these genes were impaired when Cdc5L was knocked down. Interestingly, Cdc5L is highly expressed in cervical tumors and osteosarcoma. Finally, we demonstrate that downregulation of Cdc5L decreases the cell viability of related tumor cells. These results suggest that Cdc5L is a key regulator of mitotic progression and highlight the potential of Cdc5L as a target for cancer therapy.

Tradeoff between reproduction and resistance evolution to Bt-toxin in Helicoverpa armigera: regulated by vitellogenin gene expression.

Evolution of resistance to insecticides usually has fitness tradeoffs associated with adaptation to the stress. The basic regulation mechanism of tradeoff between reproduction and resistance evolution to Bacillus thuringiensis (Bt) toxin in the cotton bollworm, Helicoverpa armigera (Ha), based on the vitellogenin (Vg) gene expression was analyzed here. The full-length cDNA of the Vg gene HaVg (JX504706) was cloned and identified. HaVg has 5704 base pairs (bp) with an open reading frame (ORF) of 5265 bp, which encoded 1756 amino acid protein with a predicted molecular mass of 197.28 kDa and a proposed isoelectric point of 8.74. Sequence alignment analysis indicated that the amino acid sequence of HaVg contained all of the conserved domains detected in the Vgs of the other insects and had a high similarity with the Vgs of the Lepidoptera insects, especially Noctuidae. The resistance level to Cry1Ac Bt toxin and relative HaVg mRNA expression levels among the following four groups: Cry1Ac-susceptible strain (96S), Cry1Ac-resistant strain fed on artificial diet with Bt toxin for 135 generations (BtR stands for the Cry1Ac Bt resistance), progeny of the Cry1Ac-resistant strain with a non-Bt-toxin artificial diet for 38 generations (CK1) and the direct descendants of the 135th-generation resistant larvae which were fed on an artificial diet without the Cry1Ac protein (CK2) were analyzed. Compared with the 96S strain, the resistance ratios of the BtR strain, the CK1 strain and the CK2 strain were 2917.15-, 2.15- and 2037.67-fold, respectively. The maximum relative HaVg mRNA expression levels of the BtR strain were approximately 50% less than that of the 96S strain, and the coming of maximum expression was delayed for approximately 4 days. The overall trend of the HaVg mRNA expression levels in the CK1 strain was similar to that in the 96S strain, and the overall trend of the HaVg mRNA expression levels in the CK2 strain was similar to that in the BtR strain. Our results suggest that the changes in reproduction due to the Bt-toxin resistance evolution in the BtR strain may be regulated by the Vg gene expression. The down-regulation of HaVg at the early stages resulted in a period of delayed reproduction and decreased fecundity in the BtR strain. This performance disappeared when the Bt-toxin selection pressure was lost.

Neuroprotective effects of LBP on brain ischemic reperfusion neurodegeneration.

AIM: The present study was conducted to investigate whether LBP had a protective effect on cerebral ischemic reperfusion injury and to determine the possible mechanisms. MATERIALS AND METHODS: Male Kunming (KM) mice were used to make the model cerebral artery occlusion/reperfusion (MCAO/R). The behavioral test was used to measure neurological deficit scores for evaluation of ischemic reperfusion damage of brain. The change of electroencephalograph (EEG) was monitored by Model SMUP-E Bio-electric Signals Processing System. The infarction area of brain was assessed in brain slices with 2% solution of 2,3,5-triphenyl tetrazolium chloride (TTC). Spectrophotometric assay was used to determine the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and lactate dehydrogenase (LDH), contents of malondialdehyde (MDA) and adenosine triphosphate (ATP) of the brain. RESULTS: The results showed that LBP at doses of 20 and 40 mg/kg markedly decreased the neurological deficit scores and the infarction area in MCAO/R mice. At the same time, LBP significantly decreased MDA content, and increased SOD, GSH-Px, CAT, LDH activities in ischemic reperfusion brain. CONCLUSIONS: These suggest that LBP might act as a potential neuroprotective agent against the cerebral reperfusion-induced injury in the brain through reducing lipid peroxides, scavenging free radicals, and improving the energy metabolism.

Newly diagnosed acute lymphoblastic leukemia in China (I): abnormal genetic patterns in 1346 childhood and adult cases and their comparison with the reports from Western countries.

It has been generally acknowledged that the diagnosis, treatment and prognosis evaluation of leukemia largely rely on an adequate identification of genetic abnormalities. A systemic analysis of genetic aberrations was performed in a cohort of 1346 patients with newly diagnosed acute lymphoblastic leukemia (ALL) in China. The pediatric patients had higher incidence of hyperdiploidy and t(12;21) (p13;q22)/ETV6-RUNX1 than adults (P<0.0001); in contrast, the occurrence of Ph and Ik6 variant of IKZF1 gene was much more frequent in adult patients (all P<0.0001). In B-ALL, the existence of Ik6 and that of BCR-ABL were statistically correlated (P<0.0001). In comparison with Western cohorts, the incidence of t(9;22) (q34;q11)/BCR-ABL (14.60%) in B-ALL and HOX11 expression in T-ALL (25.24%) seemed to be much higher in our group, while the incidence of t(12;21) (p13;q22)/ETV6-RUNX1 (15.34%) seemed to be lower in Chinese pediatric patients. The occurrence of hyperdiploidy was much lower either in pediatric (10.61% vs 20-38%) or adult patients (2.36% vs 6.77-12%) in our study than in Western reports. In addition, the frequencies of HOX11L2 in adult patients were much higher in our cohort than in Western countries (20.69% vs 4-11%). In general, it seems that Chinese ALL patients bear more adverse prognostic factors than their Western counterparts do.

An efficient compact 300 mW narrow-linewidth single frequency fiber laser at 1.5 microm.

An efficient single frequency fiber laser by using a newly-developed Er(3+)/Yb(3+) co-doped single mode phosphate glass fiber with the net gain coefficient of 5.2 dB/cm and propagation loss coefficient of 0.04 dB/cm has been demonstrated. Over 300 mW stable continuous -wave single transverse and longitudinal mode seed lasering at 1.5 microm has been achieved from a 2.0 cm-long active fiber. The measured slope efficiency and the calculated quantum efficiency of laser emission are found to be 30.9% and 0.938 +/- 0.081, respectively. It is found that the linewidth of the fiber laser is less than 2 kHz, and the measured relative intensity noise (RIN) is around -120 dB/Hz in the frequency range of 50 to 500 kHz.

Fmr1 knockout mice show reduced anxiety and alterations in neurogenesis that are specific to the ventral dentate gyrus.

Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by the selective loss of the expression of the Fmr1 gene. Key symptoms in FXS include intellectual impairment and abnormal anxiety-related behaviors. Fmr1 knockout (KO) mice exhibited reduced anxiety on two behavioral tests as well as a blunted corticosterone response to acute stress. Spatial learning and memory was not impaired when tested with both the classic Morris water and Plus-shaped mazes. Adult hippocampal neurogenesis has been associated with spatial learning and memory and emotions such as anxiety and depression. The process of neurogenesis appears abnormal in young adult Fmr1 KO mice, with significantly fewer bromodeoxyuridine-positive cells surviving for at least 4 weeks in the ventral subregion of the dentate gyrus (DG), a hippocampal subregion more closely associated with emotion than the dorsal DG. Within this smaller pool of surviving cells, we observed a concomitant increase in the proportion of surviving cells that acquire a neuronal phenotype. We did not observe a clear difference in cell proliferation using both endogenous and exogenous markers. This work indicates that loss of Fmr1 expression can alter anxiety-related behaviors in mice as well as produce region-specific alterations in hippocampal adult neurogenesis.

High performance liquid chromatographic determination of a new antifungal compound, ADKZ in rat plasma.

A high performance liquid chromatography (HPLC) method was developed and validated for the determination of ADKZ (1-(1H-1,2,4-triazole)-2-(2,4-diflurophenyl) -3-[N-methyl-N-(4-iodo-benzyl)amino]-2-propanol) in rat plasma. The compound was extracted from plasma samples by liquid-liquid extraction, and an isomeric compound of ADKZ (1-(1H-1,2,4-triazole)-2-(2,4-diflurophenyl)-3-[N-methyl-N -(3-iodo-benzyl)amino]-2-propanol) was used as the internal standard (IS), which were analyzed on a reversed-phase C18 column (5 microm, 200 mm x 4.6 mm i.d.). The extracted plasma samples were eluted with acetonitrile-0.018 M triethylamine solution adjusted to pH 3.2 with phosphoric acid (35:65, v/v). The effluent was monitored by a UV detector at 230 nm. The retention time of ADKZ was 7.1 min and IS 8.2 min. The calibration curves were linear in the concentration range of 0.02-2.00 microg/ml with the correlation coefficients greater than 0.999. The quantification limit of ADKZ in rat plasma was 0.02 microg/ml. Intra- and inter-day precision ranged from 2.6 to 7.9% and 3.1 to 9.6%, respectively. The extraction recovery from plasma was no less than 80%. No endogenous interferences were observed with either ADKZ or IS. The method has been successfully used to support the pre-clinical pharmacokinetic studies of ADKZ in rats.

Activation of dopaminergic neurotransmission in the medial prefrontal cortex by N-methyl-d-aspartate stimulation of the ventral hippocampus in rats.

Many behavioral functions-including sensorimotor, attentional, memory, and emotional processes-have been associated with hippocampal processes and with dopamine transmission in the medial prefrontal cortex (mPFC). This suggests a functional interaction between hippocampus and prefrontal dopamine. The anatomical substrate for such an interaction is the intimate interconnection between the ventral hippocampus and the dopamine innervation of the mPFC. The present study yielded direct neurochemical evidence for an interaction between ventral hippocampus and prefrontal dopamine transmission in rats by demonstrating that subconvulsive stimulation of the ventral hippocampus with N-methyl-d-aspartate (NMDA; 0.5 mug/side) activates dopamine transmission in the mPFC. Postmortem measurements revealed that bilateral NMDA stimulation of the ventral hippocampus, resulting in locomotor hyperactivity, increased the homovanillic acid/dopamine ratio, an index of dopamine transmission, in the mPFC; indices of dopamine transmission in any of five additionally examined forebrain regions (amygdala, nucleus accumbens shell/core, lateral prefrontal cortex, caudate putamen) were unaltered. In vivo microdialysis measurements in freely moving rats corroborated the suggested activation of prefrontal dopamine transmission by demonstrating that unilateral NMDA stimulation of the ventral hippocampus increased extracellular dopamine in the ipsilateral mPFC. The suggested influence of the ventral hippocampus on prefrontal dopamine may be an important mechanism for hippocampo-prefrontal interactions in normal behavioral processes. Moreover, it indicates that aberrant hippocampal activity, as found in neuropsychiatric diseases, such as schizophrenia and mood disorders, may contribute to disruption of certain cognitive and emotional functions which are extremely sensitive to imbalanced prefrontal dopamine transmission.

Regional dissociations within the hippocampus--memory and anxiety.

The amnestic effects of hippocampal lesions are well documented, leading to numerous memory-based theories of hippocampal function. It is debatable, however, whether any one of these theories can satisfactorily account for all the consequences of hippocampal damage: Hippocampal lesions also result in behavioural disinhibition and reduced anxiety. A growing number of studies now suggest that these diverse behavioural effects may be associated with different hippocampal subregions. There is evidence for at least two distinct functional domains, although recent neuroanatomical studies suggest this may be an underestimate. Selective lesion studies show that the hippocampus is functionally subdivided along the septotemporal axis into dorsal and ventral regions, each associated with a distinct set of behaviours. Dorsal hippocampus has a preferential role in certain forms of learning and memory, notably spatial learning, but ventral hippocampus may have a preferential role in brain processes associated with anxiety-related behaviours. The latter's role in emotional processing is also distinct from that of the amygdala, which is associated specifically with fear. Gray and McNaughton's theory can in principle incorporate these apparently distinct hippocampal functions, and provides a plausible unitary account for the multiple facets of hippocampal function.

Dissociation of function within the hippocampus: effects of dorsal, ventral and complete excitotoxic hippocampal lesions on spatial navigation.

The present study was designed to assess the possibility that sub-total ventral hippocampal lesions might leave intact a mechanism for only highly accurate navigation, whereas sub-total dorsal hippocampal lesions might leave intact a mechanism only for less precise navigation. Animals with selective dorsal, ventral or complete hippocampal lesions were tested in a water maze, in which the target platform was moved from trial to trial, but always within a defined area, instead of being at a fixed location. Hence, an animal that searched at exactly the point where the platform had been found on a previous trial would be disadvantaged, in comparison with an animal that searched in the right general area. This might favor animals capable of less precise navigation over those with very precise navigational abilities. In subsequent phases of the experiment, we additionally assessed, for comparison, performance with a fixed platform location, reversal learning in the water-maze, and performance on an elevated T-maze. Our results revealed no sign of any qualitative difference between the effects of the selective sub-total lesions when the water maze hidden platform location was varied within the defined area, and the effects in subsequent more conventionally used tests. Ventral hippocampal damage never led to a performance deficit. Dorsal hippocampal damage led to significantly poorer performance in only some test phases, and never led to any sign of improved performance.

Latent inhibition is spared by N-methyl-D-aspartate (NMDA)-induced ventral hippocampal lesions, but is attenuated following local activation of the ventral hippocampus by intracerebral NMDA infusion.

Repeated non-reinforced exposures of a neutral stimulus retard the development of a conditioned response to that stimulus when it is subsequently paired with a significant event. This stimulus pre-exposure effect is known as latent inhibition (LI). Early lesion studies have initially suggested an important role for the hippocampus in the normal development and expression of LI. This view has since been modified with the emergence of data derived from selective cell body lesions of the hippocampus and of the entorhinal cortex, with an abolition of LI only seen after lesions of the latter. This suggests that the significance of the hippocampus might have been overestimated in the past, possibly due to interruption of fibres en passage. However, intact behavioural expression of LI following hippocampal damage does not preclude the suggestion that the hippocampus participates in the control and regulation of LI expression in intact animals. The present study demonstrated that whilst cell body lesions of the ventral hippocampus spared LI (as expected), chemical activation of the ventral hippocampus by local N-methyl-D-aspartate infusion disrupted LI. These results parallel our earlier observations on prepulse inhibition (PPI) with similar manipulations [Neuroreport 10 (1999) 2533]. Thus, although the ventral hippocampus is itself not responsible for the behavioural manifestation of LI and PPI, it exerts at least a modulatory control over the form and/or magnitude of their expression. Our results should prompt a re-evaluation of the relative roles of the hippocampus and retrohippocampus in the development and expression of LI.

Prepulse inhibition in rats with temporary inhibition/inactivation of ventral or dorsal hippocampus.

Prepulse inhibition (PPI) of the acoustic startle response is a measure of sensorimotor gating and is decreased in neuropsychiatric diseases, including schizophrenia. Hippocampal involvement in PPI has been the subject of several studies, in particular, as aberrant hippocampal activity has been associated with schizophrenia. In rats, chemical stimulation of the ventral hippocampus reduced PPI, while normal PPI was found following hippocampal lesions, suggesting that ventral hippocampal overactivity is detrimental for PPI, but that normal hippocampal activity does not contribute substantially to PPI. In the present study, we investigated the importance of hippocampal activity for PPI by examining PPI in Wistar rats with temporarily decreased hippocampal activity, aiming to avoid compensatory processes that may occur with permanent lesions. Bilateral ventral or dorsal hippocampal infusions of the gamma-aminobutyric acid A (GABA(A)) receptor agonist muscimol (1 microg/side) or the sodium-channel blocker tetrodotoxin (TTX, 10 ng/side) reduced PPI. This reduction is probably neuroleptic-resistant since haloperidol and clozapine did not antagonize the muscimol-induced decreases in PPI. PPI reduction by muscimol inhibition or TTX inactivation of the dorsal or ventral hippocampus indicates that hippocampal activity contributes to sensorimotor gating, suggesting intact PPI after permanent hippocampal lesions to reflect compensatory processes. The data are discussed with respect to hippocampal dysfunction in schizophrenia.

The ventral hippocampus and fear conditioning in rats: different anterograde amnesias of fear after infusion of N-methyl-D-aspartate or its noncompetitive antagonist MK-801 into the ventral hippocampus.

Previous studies on hippocampal involvement in classical fear conditioning mainly focused on the dorsal hippocampus and conditioning to a context. However, in line with the strong interconnectivity of the ventral hippocampus with amygdala and nucleus accumbens, more recent studies indicated an even more global role for the ventral hippocampus in fear conditioning. The present study examined the formation of classical fear conditioning to explicit and contextual cues following stimulation or blockade of N-methyl-D-aspartate (NMDA) receptors in the ventral hippocampus. NMDA (0.5 microg/side) or the noncompetitive NMDA antagonist MK-801 (dizocilpine; 6.25 microg/side) were bilaterally infused into the ventral hippocampus of Wistar rats before fear conditioning to explicit and contextual cues. Conditioned fear was assessed using an automated measurement of freezing. NMDA stimulation of the ventral hippocampus blocked fear conditioning to both the tone and the context. MK-801 selectively blocked fear conditioning to the context. Our results support that the ventral hippocampus plays a role in the formation of classical fear conditioning. The specific anterograde amnesia for fear to a context after MK-801 infusion into the ventral hippocampus indicates that formation of classical fear conditioning to a context but not to a tone requires activation of NMDA receptor-mediated processes in the ventral hippocampus. Given that NMDA stimulation of the ventral hippocampus disrupts also processes not mediated by NMDA receptors, the complete anterograde amnesia following NMDA infusion into the ventral hippocampus might be due to the concurrent severe disruption of normal ventral hippocampal activity. However, strong stimulation of the ventral hippocampus might also disrupt fear conditioning by interfering with processes in the projection areas of the ventral hippocampus, such as the amygdala or the nucleus accumbens. In addition, we report that MK-801 (6.25 microg/side) infusion into the ventral hippocampus increased locomotor activity in the open field.

Hyperactivity, decreased startle reactivity, and disrupted prepulse inhibition following disinhibition of the rat ventral hippocampus by the GABA(A) receptor antagonist picrotoxin.

RATIONALE: Functional imaging studies have revealed overactivity of the hippocampus in schizophrenic patients. Neuropathological data indicate that hyperactivity of excitatory hippocampal afferents and decreased hippocampal GABA transmission contribute to this overactivity. In rats, excitation of the ventral hippocampus, e.g. by NMDA, results in hyperactivity and disruption of sensorimotor gating measured as prepulse inhibition (PPI) of the acoustic startle response, behavioral effects related to psychotic symptoms in humans. OBJECTIVE: The present study examined whether disinhibition of the ventral hippocampus by the GABA(A) antagonist picrotoxin would result in similar psychosis-related behavioral disturbances (hyperactivity, decreased PPI) as NMDA stimulation. METHODS AND RESULTS: Wistar rats received bilateral infusions of subconvulsive doses of picrotoxin (100 or 150 ng/0.5 microl per side) into the ventral hippocampus and were then immediately tested for open field locomotor activity or startle reactivity and PPI. Only the higher dose induced hyperactivity and decreased PPI. Both doses decreased acoustic startle reactivity to a similar extent. The decreased PPI appeared not to result from decreased startle reactivity, but was associated with a diminished potency of the prepulses to inhibit the startle reaction to the startle pulse, indicating a sensorimotor gating deficit. All effects were temporary, i.e. disappeared when the rats were tested 24 h after infusion. CONCLUSIONS: Decreased GABAergic inhibition in the ventral hippocampus of rats yielded psychosis-related behavioral effects, very similar to those induced by NMDA stimulation. Thus, a concurrence of decreased GABAergic inhibition and increased afferent excitation in the hippocampus of schizophrenic patients might contribute to psychotic symptoms.