The effect of prenatal morphine exposure on memory consolidation in the chick

The central nervous system exhibits remarkable plasticity in early life and can be altered significantly by prenatal morphine exposure. Previous studies show that prenatal morphine exposure may alter the capacity for learning and memory in post-partum chicks. The one-trial passive avoidance learning paradigm with 1-day-old chicks is an excellent model to study several mechanisms of memory formation, including STM, ITM, and LTM. The following represents our investigation of the effect of prenatal morphine exposure on learning and memory deficits in the chick. In these experiments, morphine was injected into the airspace of eggs (20 mg/kg) and the one-trial passive avoidance learning paradigm was used to test the effect of prenatal morphine exposure on memory consolidation. The data suggest that chicks injected with morphine daily from E12 to E16 had significantly impaired long-term memory at 120 min after training (p < 0.001) but not intermediate-term memory at 30 min after training.     

The effects of morphine at different embryonic ages on memory consolidation and rewarding properties of morphine in day-old chicks

Prenatal exposure to morphine can alter the capacities for learning and memory and the sensitivity to drugs of abuse in progeny. In the present study, we examined the effects of morphine during chick embryonic period of 5–8, 9–12, 13–16 and 17–20 on cognitive function and the sensitivities to morphine reward in the post-hatch chick, using the one-trial passive avoidance learning task and the conditioned place preference paradigm. It was observed that the injection of morphine (1 mg/kg of egg weight) during E5–8, but not in other three periods, significantly impaired intermediate- and long-term memory in one-day-old chicks. On the other hand, the chicks prenatally exposed to morphine during E17–20 remarkably not only acquired but also maintained the conditioned place preference induced by morphine. The present results suggest that there are two time-windows during development, which in the chick are around E5–8 and E17–20, when prenatal morphine exposure is likely to confer maximal risks for vulnerabilities to breakdown of memory consolidation and to morphine-induced reward in day-old chicks respectively.     

Effects of prenatal exposure to antithyroid drugs on imprinting behavior in chicks

Thyroid hormones play important roles in vertebrate brain development. However, there is little understanding of the direct effects of fetal thyroid dysfunction, i.e., not acquired through the mother, on learning ability. In the present study, we use a chick embryo as a fetal model to investigate the effects of prenatal exposure to antithyroid drugs on imprinting behavior in hatched chicks. Methimazole (MMI) at 20 µmol/egg or 5 µmol/egg of propylthiouracil (PTU) was administered to eggs on day 14 while the control was given only a vehicle. An imprinting test was conducted after the chicks hatched. Day-old chicks were exposed to a rotating training object for 150 min. The next day, the trained chicks were exposed to the training object and a novel object. The imprinting preference was represented as a preference score (PS) calculated as the rate of following the training object to following the training and novel objects. In the MMI-treated chicks, the PS was 0.68 ± 0.06 (range, 0.38-0.88), which was significantly lower than that in the control chicks (0.86 ± 0.04, p < 0.01). In the PTU-treated chicks, the PS was 0.69 ± 0.04 (range, 0.52-0.89), which was also significantly lower than that in the control (0.88 ± 0.02, p < 0.001). The present findings suggested that fetal thyroid dysfunction inhibited brain development, leading to impaired learning and memory. Our chick model can be considered useful for investigating the direct effects of prenatal exposure to antithyroid drugs or substances in the environment on learning ability after birth.     

Transient increase in forebrain muscarinic cholinergic receptor binding following passive avoidance learning in the young chick

The concentration of the muscarinic cholinergic receptor in two regions of the chick brain was measured by atropine-sensitive binding of the ligand [³H]quinuclidinyl benzilate at varying times after training 1–2 day old chicks on a one-trial passive avoidance task. Thirty min after training, there was a 21% increase (P < 0.001) in [³H]quinuclidinyl benzilate binding/mg protein in the chick fore brain, though not the optic lobes. The elevation was not significant at 10 min after training and had disappeared in 3 h. The elevation could not be induced merely by making the birds taste the aversive stimulus, methylanthranilate, whilst agents which disrupted acquisition and memory, ouabain and cyclo heximide, also abolished the training-induced rise in [³H]quinuclidinyl benzilate binding activity.We suggest that increased [³H]quinuclidinyl benzilate binding in the chick forebrain is a correlate of the early phases of memory fixation.     

The impairment of one-trial passive avoidance learning in chicks caused by prenatal aluminum exposure

Prenatal aluminum exposure may affect the development of the embryo and alter the capacity for learning and memory in adults. The chick embryo is a good experimental model to study the effect of prenatal toxin exposure on cognitive defects in offspring, because it eliminates maternal confounding variables. In the present study, we applied a one‐trial passive avoidance‐learning task in day‐old chicks to examine the effects of prenatal aluminum chloride injections (2, 20, and 200 mM in 200 µl per egg, daily over a period of 4 successive days) on memory consolidation. The data suggest that chicks injected with aluminum chloride (20 mM) daily from E12 to E15 had significantly impaired short‐term memory, intermediate‐term memory, and long‐term memory (LTM) after training (p < .05) but chicks injected with aluminum chloride (2 mM) had impaired LTM only. © 2011 Wiley Periodicals, Inc. Dev Psychobiol 54:133‐138, 2012.     

Ouabain does not impair reconsolidation following a reminder of passive avoidance learning in the day-old chick

This study investigated the effect of ouabain, an inhibitor of NA⁺ and K⁺ ATPase, on consolidation and reconsolidation of a passive avoidance learning task in the day-old chick. In the consolidating trace, ouabain is thought to inhibit an intermediate-term memory phase, some aspects of which acts as a “trigger” for long-term stabilisation of the trace by new protein synthesis. It was hypothesised that a similar process may initiate the protein synthesis observed following reminder-activated reconsolidation in the young chick. Chicks were trained on a single trial passive avoidance task. A dose of 0.2 ug/kg ouabain was administered intracranially either 5 min post-training (consolidation processes) or 5 min post-reminder (reconsolidation processes). Consistent with previous research, ouabain administration induced a memory deficit following the initial learning trial. However, contrary to expectation, ouabain did not disrupt memory processing post-reactivation. This finding provides further evidence for the notion that consolidation and reconsolidation are associated with similar, but distinct, stages of processing.     

Comparisons of insulin related parameters in commercial-type chicks: Evidence for insulin resistance in broiler chicks

The aim of this study is to elucidate whether insulin acts differentially within the central nervous system (CNS) of two types of commercial chicks to control ingestive behavior. Male layer and broiler chicks (4-day-old) were intracerebroventricularly (ICV) injected with saline or insulin under satiated and starved conditions. Feed intake was measured at 30, 60 and 120 min after treatment. Secondly, blood and hypothalamus were collected from both chick types under ad libitum feeding and fasting for 24 h. Plasma insulin concentration was measured by time-resolved fluoro-immunoassay. Hypothalamic insulin receptor mRNA expression levels were measured by quantitative RT-PCR. The ICV injection of insulin significantly inhibited feed consumption in layer chicks when compared with saline (P < 0.05), but not broiler chicks (P > 0.1). Plasma insulin concentration of both chick types significantly decreased following 24 h of fasting, while insulin concentrations in the broiler chicks were significantly higher compared to the layers fed under ad libitum conditions. Hypothalamic insulin receptor mRNA expression levels were significantly lower (P < 0.05) in broiler chicks than in layer ones under ad libitum feeding. Feed deprivation significantly decreased insulin receptor mRNA levels in layer chicks (P < 0.01), but not in broiler chicks (P > 0.1). Moreover, plasma insulin concentrations correlated negatively with hypothalamic insulin receptor protein expression in the two types of chicks fed ad libitum (P < 0.05). These results suggest that insulin resistance exists in the CNS of broiler chicks, possibly due to persistent hyperinsulinemia, which results in a down-regulation of CNS insulin receptor expression compared to that in layer chicks.     

Central ghrelin acts as an anti-dipsogenic peptide in chicks

The aim of this study was to look at whether ghrelin has an anti-dipsogenic effect, as seen in the eel, when administered centrally in neonatal chicks. Intracerebroventricular (ICV) injection of chicken ghrelin inhibited water intake (WI) in chicks under both ad libitum and 17-h water-deprived drinking conditions at doses ranging from 0.01 to 0.1 nmol/chick. This inhibitory effect was observed when 0.1 nmol of rat ghrelin was injected. On the other hand, 0.1 nmol des-acyl rat ghrelin did not reduce WI. To examine the mechanism underlying the effect of ghrelin on WI, chicken B-type (or brain) natriuretic peptide (BNP), an anti-dipsogenic peptide in mammals, was injected at doses ranging from 0.1 to 1 nmol/chick. BNP did not affect WI in chicks under both normal and water-deprived drinking conditions. These findings indicate that ghrelin acts as an anti-dipsogenic peptide through the GHS receptor in the chicken.     

Role of brain-derived neurotrophic factor and presynaptic proteins in passive avoidance learning in day-old domestic chicks.

The consolidation of a one-trial passive avoidance learning task in the day-old chick involves a number of transient and longer-term biochemical processes, including increased release of glutamate. This study demonstrated that brain-derived neurotrophic factor, a proposed modulator of synaptic transmission and neurotransmitter release, is involved in the cascade associated with memory consolidation in the chick and that its actions were linked to modulation of expression of SNAP-25, syntaxin and synaptophysin, required for exocytosis. Intracerebral injections of 5 microl of antibodies to brain-derived neurotrophic factor into the left and right intermediate medial hyperstriatum ventrale resulted in a dose-dependent reduction in avoidance of an "aversive" bead by 3 h after training. Neurotrophin antibodies (0.5 microg/chick) administered between 1 h before, and up to 30 min after, training induced amnesia by 3 h which was sustained for at least 24 h. Injections of recombinant brain-derived neurotrophic factor (50 microg/ml; 0.5 microg/chick) just before training maintained avoidance in birds trained with a weaker aversant (10% methylanthranilate), such that chicks showed enhanced recall at times (24 h) beyond that when shorter-term forms of memory have decayed. In lysed synaptosomal membranes prepared from chicks injected with antibodies to brain-derived neurotrophic factor there was a decrease in expression of SNAP-25 and syntaxin in the left, but not the right, intermediate medial hyperstriatum ventrale, a region known to be associated with memory formation, which correlated with the decrease in neurotrophin concentration. Thus, these data indicate that brain-derived neurotrophic factor is involved in the formation of a long-term memory for an aversive stimulus and may function as a modulator of presynaptic proteins associated with exocytosis, enabling increases in neurotransmitter release.     

Nelumbo nucifera semen extract improves memory in rats with scopolamine-induced amnesia through the induction of choline acetyltransferase expression

Nelumbo nucifera semen (NNS) is a traditional herb with anti-diarrheal, anti-ganacratia, and tranquilizer-like pharmacological activities. In this study, we examined the anti-amnesic effect of NNS on rats with scopolamine-induced amnesia. Passive avoidance tests, acetylcholinesterase (ACHE) activity, and choline acetyltransferase (CHAT) expression were used to evaluate the NNS anti-amnesic effects. The rats were divided into five groups: the normal group, scopolamine-treated group (1 mg/kg; control), NNS (1 g/kg) and scopolamine (1 mg/kg) co-treatment group, and the ARICEPT (1 mg/kg) and scopolamine (1 mg/kg) co-treatment group (positive control). The rats were administered the compounds orally for 14 days. The latency time of passive avoidance significantly increased by 54% in the NNS-treated group compared to the scopolamine-treated group. The ACHE activity in the NNS-treated group significantly decreased to 7.35% than that of the control group. CHAT-positive neurons increased by 51.02% in the NNS group compared to the control group. These results suggest that NNS extract improves scopolamine-induced dementia by inhibiting ACHE activity and inducing CHAT expression.     

Prenatal endotoxin exposure alters behavioural pain responses to lipopolysaccharide in adult offspring

Evidence suggests that exposure to bacterial endotoxin in early life can alter the production of pro-inflammatory cytokines in later life. This phenomenon may have significant consequences for pain and pain related behaviours as pro-inflammatory cytokines heighten pain sensitivity. This association has yet to be examined. As such, the aim of the present study was to characterize pain behaviours in adult rat offspring following prenatal endotoxin (PE) exposure. Pregnant F344 rats received endotoxin (200 µg/kg, s.c.) or saline on gestational days 16, 18 and 20. Pain thresholds were assessed in the adult PE offspring (n = 23) and control offspring (n = 24) prior to and 4 h following administration of lipopolysaccharide (LPS; 100 µg/kg, s.c.). Three assays of pain were employed — the hot plate, tail immersion and von Frey tests. Results demonstrated sex-specific effects of prenatal endotoxin on the offspring, with PE males displaying unaltered pain thresholds on the von Frey test post-LPS administration (p < 0.01), while male control offspring (n = 24) displayed the expected hyperalgesia. Male PE offspring also displayed increased pain thresholds on the tail immersion test (p < 0.01), while no change in pain sensitivity was observed in control males following LPS exposure. No difference in response was observed between the female PE and control offspring on the von Frey test, however PE female offspring displayed increased thresholds on the tail immersion test compared to baseline — an effect not observed in the control female offspring. Pain sensitivity on the hot plate test was unaffected by prenatal exposure to endotoxin. These data suggest that prenatal exposure to products associated with bacterial infection have the capacity to alter pain responses, which are evident in the adult offspring.     

Ameliorative effect of vitamin C on the haematological changes induced by exposure of chlorpyriphos and lead acetate in Wistar rats

The present study was designed to evaluate the effects of chlorpyriphos, lead acetate and vitamin C alone and in combinations, on various haematological parameters in Wistar rats. Rats of 150–200 g body weight were divided into eight groups of six animals each and were subjected to various daily oral treatment regimes for 98 days. Group C served as control receiving only corn oil, group CP received chlorpyriphos at 5.5 mg/kg in corn oil and group L received lead acetate at100?ppm in water, whereas animals in group CP + L received a combination of chlorpyriphos at 5.5 mg/kg in corn oil and lead acetate at 100 ppm in water. Group VC received vitamin C at 100 mg/kg in water; group CP + VC received a combination of chlorpyriphos at 5.5 mg/kg and vitamin C at 100 mg/kg; group L + VC received lead acetate at 100 ppm in water and vitamin C at 100 mg/kg and group CP + L + VC received chlorpyriphos at 5.5 mg/kg, lead acetate at 100 ppm in water and vitamin C at 100 mg/kg. Blood samples were collected on days 0, 30, 60 and 98 post exposure and analysed for packed cell volume (PCV), total erythrocyte count (TEC), haemoglobin (Hb), erythrocyte sedimentation rate (ESR), total leucocyte count (TLC) and differential leucocyte count. A significant decrease in TEC, PCV and Hb and a significant increase in ESR values were observed. However, lead acetate caused an increase in TLC while chlorpyriphos resulted in a decrease in TLC. Both of these toxicants potentiated toxicity of each other. The study demonstrated that treatment of chlorpyriphos- and lead-treated rats with vitamin C significantly altered some of the important haematological parameters revealing the protective effect of this vitamin against haematological alterations induced by chlorpyriphos and lead.     

Responsiveness to methamphetamine in adulthood is altered by prenatal exposure in rats

Methamphetamine (MA) is a drug causing potent psychomotor activation. The aim of the present study was: (1) to assess the effect of prenatal and acute MA administration on behavior in adult male rats and (2) to find out if the prenatal exposure to MA increases sensitivity to acute MA application in adulthood.Behavior of adult male rats prenatally exposed to MA (5 mg/kg) or saline was tested in Open field (OF) and Elevated plus maze (EPM). Subcutaneously administered MA (1 mg/kg) or saline were used as challenge in adulthood, 30 min prior to testing.Our results showed that prenatal MA did not have an effect on baseline behavior in either of the tests. By contrast, acute MA increased overall psychomotor activity by increasing locomotion and exploratory behavior and decreasing comforting behavior. Moreover, adult rats prenatally exposed to MA exhibited increased sniffing and decreased rearing after acute MA dose in adulthood relative to prenatally saline-exposed rats. In addition, while acute MA application decreased anxiety in rats prenatally exposed to MA, rats prenatally exposed to saline were less sensitive to the anxiolytic effects of MA.Our results indicate that changes caused by prenatal exposure to psychostimulants may become apparent as different reactivity to drugs of abuse when an individual encounters them later in life. In addition, we found that the anxiolytic effect of acute MA (1 mg/kg) probably depends also on the reactivity to stress and the activity of hypothalamo-pituitary-adrenal axis.     

Temporal effects of dehydroepiandrosterone sulfate on memory formation in day-old chicks

Dehydroepiandrosterone sulfate (DHEAS) has been shown to enhance memory retention in different animal models and in various learning paradigms. In the present study, we investigated the effect of peripherally administered DHEAS on the acquisition, consolidation and retention of memory using a weak version of the one-trial passive avoidance task in day-old chicks. Intraperitoneally administered DHEAS (20 mg/kg) either 30 min before or 30 min and 4.5 h after training on the weakly aversive stimulus, enhanced recall at 24 h following training, suggesting a potentiation of not only the acquisition but also the early and late phases of memory consolidation. In contrast, when DHEAS was administered at 30 min prior to the 24 h retention test there was no memory enhancement, indicating a lack of effect on memory retrieval. Memory recall was unaltered when DHEAS was administered at 30 min before training in a control group trained on a strongly aversive stimulus, confirming memory-specific effects. Interestingly, the memory enhancement appeared to be sex-specific as male chicks showed higher recall than females. These findings provide further evidence that DHEAS enhances memory and may be involved in the temporal cascade of long-term memory formation.     

NMDA receptor antagonists extend the sensitive period for imprinting

Filial imprinting in the domestic chick occurs during a sensitive period of development. The exact timing of this period can vary according to the methods used to measure imprinting. Using our imprinting paradigm, we have shown that normal, dark-reared chicks lose the ability to imprint after the second day post-hatching. Further, we reported that chicks treated 10 h after hatching with a mixture of the noncompetitive NMDA receptor antagonist ketamine (55 mg/kg) and the alpha(2)-adrenergic receptor agonist xylazine (6 mg/kg) were able to imprint on day 8 after hatching, whereas controls treated with saline did not imprint. We now show that the effect of the ketamine-xylazine mixture can be mimicked by treating chicks with ketamine alone or with another noncompetitive NMDA receptor antagonist, MK-801 (5 mg/kg). Treating chicks with a single dose of ketamine (55 mg/kg) or with a single dose of xylazine (6 mg/kg) failed to produce the effect on the sensitive period. However, prolonging the action of ketamine by treating chicks with two doses of ketamine (at 10 and 12 h after hatching) did allow imprinting on day 8. In contrast, prolonging the action of xylazine had no effect on the sensitive period for imprinting. Chicks treated with MK-801 were also able to imprint on day 8. Thus, we have evidence that the NMDA receptor system is involved in the mechanisms that control the sensitive period for imprinting.     

Biased embryos: Prenatal experience alters the postnatal malleability of auditory preferences in bobwhite quail

Many precocial birds show a robust preference for the maternal call of their own species before and after hatching. This differential responsiveness to species-specific auditory stimuli by embryos and neonates has been the subject of study for more than four decades, but much remains unknown about the dynamics of this ability. Gottlieb [Gottlieb [1971]. Development of species identification in birds: An enquiry into the prenatal determinants of perception. Chicago/London: University of Chicago Press.] demonstrated that prenatal exposure to embryonic vocalizations serves to canalize the formation of species-specific preferences in ducklings. Apart from this, little is known about the features of the developmental system that serve to canalize such species-typical preferences, on the one hand, and generate novel behavioral phenotypes, on the other. In the current study, we show that briefly exposing bobwhite quail embryos to a heterospecific Japanese quail (JQ) maternal call significantly enhanced their acquisition of a preference for that call when chicks were provided with subsequent postnatal exposure to the same call. This was true whether postnatal exposure involved playback of the maternal call contingent upon chick contact vocalizations or yoked, non-contingent exposure to the call. Chicks that received both passive prenatal and contingent postnatal exposure to the JQ maternal call redirected their species-typical auditory preference, showing a significant preference for JQ call over the call of their own species. In contrast, chicks receiving only prenatal or only postnatal exposure to the JQ call did not show this redirection of their auditory preference. Our results indicate that prenatal sensory stimulation can significantly bias postnatal responsiveness to social stimuli, thereby altering the course of early learning and memory.     

Water T-maze,an improved method to assess spatial working memory in rats: Pharmacological validation

The present study was performed to validate a spatial working memory task using pharmacological manipulations. The water escape T-maze combines the advantages of the Morris water maze and the T-maze while minimizing the disadvantages. Scopolamine (1 mg/kg), a drug that affects cognitive function in spatial working memory tasks, significantly decreased the rats’ performance in the present delayed alternation task. Glutamate neurotransmission plays an important role in the maintenance of working memory; rats treated with dizocilpine (MK-801; 0.125–0.25 mg/kg), a N-methyl-d-aspartate (NMDA) receptor antagonist, were impaired in this task. In agreement with evidence showing a functional interaction between ionotropic and metabotropic glutamatergic receptors, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a mGlu₅ receptor antagonist, at a dose (1 mg/kg) which by itself had no significant effects, enhanced MK-801-induced impairments of spatial working memory. These evidences suggest that the water escape T-maze might be a valid method to assess spatial working memory, sensitive to pharmacological manipulations.     

Lead and Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms: A meta-analysis

This meta-analysis examined the association between Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms and lead exposure in children and adolescents. Thirty-three studies published between 1972 and 2010 involving 10,232 children and adolescents were included. There was a small to medium association between inattention symptoms and lead exposure (r = .16, k = 27, p < .001) and a similar association between hyperactivity/impulsivity symptoms and lead exposure (r = .13, k = 23, p < .001). There was significant heterogeneity among the effect sizes for both inattention symptoms and for hyperactivity/impulsivity symptoms, with studies using hair analysis to assess lead burden yielding substantially larger effect sizes than those using other methods. Excluding the hair analysis studies, the average rs were .14 for inattention (k = 23, p < .001) and .12 for hyperactivity/impulsivity (k = 21, p < .001). Overall, the relation between lead exposure and ADHD symptoms was similar in magnitude to the relation between lead exposure and decreased IQ and between lead exposure and conduct problems.     

Selective Impairments to Memory Consolidation in Chicks Produced by 5′-Iodo-2′-Deoxyuridine

The aim of the present work was to study the role of DNA synthesis in the formation of different types of memory in neonatal chicks. The nucleotide analogs 5′-iodo-2′-deoxyuridine (IdU) and 5′-bromo-2′-deoxyuridine (BrdU) were used; these are incorporated into DNA, impairing its function, and have amnestic actions in defined models of learning in mice. We studied the effects of 5′-iodo-2′-deoxyuridine of the formation of long-term memory in chicks during training in different models: passive avoidance, imprinting, taste aversion, and spatial learning in a maze. In the taste aversion model, i.p. administration of IdU (10 mg/kg 5 min before or 50 min after training) had an amnestic effect on testing 1–2 days after training. IdU-induced amnesia developed more than 6 h after training, while administration of IdU 2 h after training had no amnestic effect. 5′-Bromo-2′-deoxyuridine also had a similar amnestic action in the taste aversion model. In the passive avoidance, imprinting, and spatial maze learning models, administration of IdU at the same dose before and after training did not induce amnesia. These data lead to the suggestion that DNA synthesis in the brain may play a critical role in the mechanisms of memory consolidation in chicks in types of learning such as taste aversion.     

母鼠孕哺期铅暴露及补充铁、钙对子代神经系统的影响

目的观察孕哺期铅暴露及补充铁和钙对子代学习记忆能力及海马细胞中生长抑素（SS）表达的影响。方法母鼠从孕期第1天至仔鼠出生第30天哺乳期间给以下干预：对照组（A）：饮用去离子水;染铅组（B）：饮用浓度为0．1％醋酸铅去离子水;铁＋铅组（C）：饮用浓度为0．1％醋酸铅的去离子水同时每天灌胃3．0mg／kg铁;铁＋钙＋铅组（D）：饮用浓度为0．1％醋酸铅的去离子水同时每天灌胃3．0mg／kg铁和250mg／kg钙。Y-迷宫试验用于检测仔鼠的学习记忆能力,采用免疫组织化学的方法观察仔鼠海马细胞中生长抑素（SS）阳性神经元。结果B组与A组比较,仔鼠Y-迷宫试验的错误次数明显增多（P〈0．05）,海马CA1、CA3区SS阳性神经元数量减少（P〈0．05）。D组Y-迷宫试验的错误次数比B组明显减少（P〈0．05）,海马CAI区SS阳性神经元数量增多,有统计学意义（P〈0．05）。C组则未表现上述变化。结论孕哺期母体铅暴露会损害仔鼠的学习记忆能力,补充钙剂可有所改善,而补充铁则没有明显改变,并能从海马组织中SS表达的改变得到印证。