Maternal exposure to bacterial endotoxin during pregnancy enhances amphetamine-induced locomotion and startle responses in adult rat offspring

An increased incidence of schizophrenia has been associated with several perinatal insults, most notably maternal infection during pregnancy and perinatal hypoxia. This study used a rat model to directly test if maternal exposure to bacterial endotoxin (lipopolysaccharide, LPS) during pregnancy alters behaviors relevant to schizophrenia, in offspring at adulthood. The study also tested if postnatal anoxia interacted with gestational LPS exposure to affect behavior. At adulthood, offspring from dams administered LPS on days 18 and 19 of pregnancy showed significantly increased amphetamine-induced locomotion, compared to offspring from saline-treated dams. A period of anoxia on postnatal day 7 had no effect on amphetamine-induced locomotion and there was no interaction between effects of gestational LPS and postnatal anoxia on this behavior. Offspring from LPS-treated dams also showed enhanced acoustic startle responses as adults, compared to offspring from saline-treated dams. In offspring tested for pre-pulse inhibition (PPI) of acoustic startle and for apomorphine modulation of PPI, no effects of either gestational LPS or of postnatal anoxia and no interactions between LPS and anoxia were observed. It is concluded that maternal LPS exposure during pregnancy in the rat may be a useful model to study mechanisms responsible for effects of maternal infection on behaviors relevant to schizophrenia, in offspring.     

Repeated stress, like vasopressin, sensitizes the excitatory effects of corticotropin releasing factor on the acoustic startle reflex

In the rat, evidence now suggests a neurotransmitter function for the neuropeptides arginine vasopressin (AVP) and corticotropin releasing factor (CRF), implicating them in various autonomic, behavioral, and neuroendocrine responses to stress. Repeated AVP/CRF release in the pituitary portal circulation, due to stress, sensitizes and potentiates the release of ACTH from the anterior pituitary. Using a neuroanatomically well-defined behavior, the acoustic startle reflex in the rat, we sought to determine whether an interaction between AVP, CRF and stress might also occur centrally as measured by increased behavioral sensitivity to AVP or CRF given directly into the brain. The first experiment tested whether repeated intraventricular (i.c.v.) infusion of AVP would lead to an increase in the excitatory effect of a subthreshold dose of AVP on the acoustic startle reflex when infused 48 h later. Different groups of rats were infused with various doses of AVP (0.3, 3, or 30 ng) or vehicle on Day 1 and tested for startle over the next 60 min. On Day 2, 48 h later, all animals were infused with a single dose of AVP (300 pg) and tested for startle. Infusion of AVP on Day 1 did not increase startle consistently at any dose, but did lead to a sensitized excitatory effect of AVP on startle on Day 2 which was non-monotonically related to the dose of AVP given on Day 1. Experiment 2 tested whether AVP on Day 1 would sensitize the excitatory effects on startle of CRF given i.c.v. on Day 2. Different groups of rats were infused i.c.v. with various doses of AVP (10, 30, 100, 300 pg) or vehicle on Day 1. On Day 2, 48 h later, all rats were infused with a subthreshold dose of CRF (0.25 μg). Infusion of AVP on Day 1 led to a sensitized excitatory effect of CRF on startle on Day 2 which was non-monotonically related to the dose of AVP given on Day 1. In experiment 3, we tested whether footshocks given on Day 1 would sensitize the excitatory effect of CRF on startle tested 48 h later. Different groups were given footshocks (0.2, 0.4, 0.8, 1.6 mA) on Day 1. On Day 2, 48 h later, all rats were infused with a subthreshold dose of CRF (0.25 μg). Footshocks given on Day 1 led to a sensitized excitatory effect of CRF on startle on Day 2 which was non-monotonically related to the intensity of footshock on Day 1. Taken together, these results suggest that an interaction between AVP, CRF and stress may occur centrally, consistent with other studies showing similar interactions peripherally. This may provide a model system for analyzing how prior stress leads to enhanced behavioral reactions to subsequent stressors and a mechanism to explain dysregulation of the stress response.     

Neonatal lipopolysaccharide and adult stress exposure predisposes rats to anxiety-like behaviour and blunted corticosterone responses: Implications for the double-hit hypothesis

The double-hit hypothesis posits that an early life genetic or environmental insult sets up a neural predisposition to psychopathology, which may emerge in the presence of a subsequent insult, or ‘second hit’ in later life. The current study assessed the effect of neonatal lipopolysaccharide (LPS) exposure on anxiety-like behaviours in the adult Wistar rat. Rats were administered either LPS (Salmonella enterica, serotype enteritidis, 0.05 mg/kg, ip) or saline (equivolume) on days 3 and 5 of life (birth = day 1). In adulthood (85 days), subjects were allocated to either “stress” or “no stress” treatment groups. For the “stress” group, subjects were exposed to a three-day stress protocol consisting of a 30 min period of restraint and isolation. The “no stress” group was left unperturbed but were handled during this period to control for handling effects between adult “stress” and “no stress” conditions. All animals then underwent behavioural testing using standardised tests of anxiety-like behaviour, including either the Hide Box/Open Field, Elevated Plus Maze (EPM) or Acoustic Startle Response (ASR). Time and event measures for restraint and isolation, the Hide Box/Open Field and EPM were recorded using automated tracking software. Startle amplitude and habituation across time was measured in the ASR test. Prior to and following behavioural test sessions, peripheral blood was collected to assess serum corticosterone and ACTH levels. Data analysis indicated that LPS-treated animals exposed to stress in adulthood exhibited increased anxiety-like behaviour across all behavioural tests compared to controls. Sexually dimorphic effects were observed with males exhibiting increased anxiety-related behaviours compared to females (p < .05). Neonatal LPS exposure induced a significant increase in corticosterone compared to controls (p < .05), whereas corticosterone responses to stress in adulthood were associated with a significantly blunted HPA axis response (p < .05). No differences in ACTH were observed. These results lend support to the double-hit hypothesis of anxiety-related behaviour, demonstrating that neonatal immune activation produces an enhanced propensity toward anxiety-related behaviour following stress in adulthood, and that this susceptibility is associated with alterations to HPA axis ontogeny.     

Anatomical distribution and response patterns of reticular neurons active in relation to acoustic startle

A population of reticulospinal neurons with short latency response to startle-inducing stimuli was identified in the nucleus reticularis pontis caudalis (NRPC) and nucleus gigantocellularis (NRGC) of the medial pontomedullary reticular formation. The threshold and magnitude of response to auditory stimuli was correlated in these cells and in the muscles mediating startle. Startle-related neurons were significantly more likely to have high conduction velocity spinal projections than adjacent cells not related to startle. Startle-related cells were not 'dedicated' to startle, but were active in relation to spontaneous movements. Both the unit response of the startle-related cells and the startle response recorded in muscles were suppressed by the prior presentation of a weak prepulse. Thus, prepulse inhibition of startle occurs at, or prior to, the medial pontomedullary reticular formation. We conclude that these reticulospinal cells convey the output of the brainstem system modulating and triggering startle.     

Effects of various direct or indirect dopamine agonists on the latency of the acoustic startle response in rats

Summary The effects of dopamine agonists were investigated on the latency of the acoustic startle response in male Wistar rats. Four indirect dopamine agonits were tested: GBR 12783 (5–20mg/kg), BTCP (5–20mg/kg), dexamphetamine (3–6mg/kg) and L-DOPA 100 mg/kg associated with benserazide 25 mg/kg; they induced an increase in startle latency. Apomorphine at a dose (50 g/kg) known to decrease dopaminergic transmissions, was ineffective on the startle response. On the contrary, at 0.6 or 2 mg/kg, apomorphine induced an increase in the startle latency. A similar effect was observed with bromocriptine at 10 mg/kg from the 10th min up to at least the 9th hour after treatment. The specific agonist of D2 receptors Ru 24926 (0.45 mg/kg) enhanced the startle latency as well as the specific agonist of D1 receptors SKF 38393 (10 mg/kg). The association of these drugs resulted in an apparent additivity of their individual effects. The effect of apomorphine (0.6 mg/kg) was only partially reduced by a high dose of the specific D2 antagonist amisulpride (80 mg/kg) and more clearly antagonized by the specific D1 antagonist SCH 23390 (50 g/kg). It is concluded that D2 and D1 receptors contribute to the increase in startle latency elicited by direct or indirect dopamine agonists.     

Re-exposure to endotoxin induces differential cytokine gene expression in the rat hypothalamus and spleen

This study was designed to investigate whether the pattern of hypothalamic and splenic cytokine expression induced by peripheral administration of a bacterial lipopolysaccharide (LPS) is affected by prior exposure to LPS derived from another bacterial strain. Injection of LPS from Salmonella enteritidis (LPS₂) alone resulted in increased hypothalamic gene expression of IL-1β, IL-6, TNFα, IL-1ra and IL-10. However, pre-exposure to LPS derived from Escherichia coli (LPS₁) 3 weeks before, significantly attenuated hypothalamic IL-1ra, IL-6 and IL-10 expression. IL-1β expression also tended to be lower. This pattern contrasted with the robust cytokine expression in the spleen of LPS₂-treated rats previously exposed to LPS₁, since pre-treatment with endotoxin resulted in a significantly greater response of IL-1β and IL-1ra to LPS₂. Expression of TNFα and IL-10 also tended to be higher. Pre-treatment with LPS₁ did not significantly affect the marked increase in corticosterone and adrenaline blood levels induced by LPS₂. Thus, while endotoxin pre-exposure seemed not to induce a “tolerant” state in the periphery as judged by the immune and endocrine parameters evaluated upon re-stimulation, expression of four of the six cytokines measured was decreased in the hypothalamus. This is the first demonstration that endotoxin priming can differentially affect cytokine expression in the central nervous system and peripheral tissues when a host is confronted with a second, acute, pro-inflammatory stimulus. These results may provide new evidence for the involvement of cytokine pathways in the central nervous system in modulating peripheral inflammation and mediating cognitive and behavioural alterations during inflammatory diseases.     

The influence of stimulus repetition on the acoustic startle response and on responses of inferior colliculus neurons of mice

The acoustic startle response (ASR) and discharges of single units in the inferior colliculus (IC) were evaluated as a function of the repetition rate and trial (stimulus 1–10 at each rate) of intense noise bursts in mice. The amplitude of the ASR was inversely proportional to both rate and trial. The mean number of discharges for the sample population of units of the central nucleus (ICC) and the external nucleus (ICX) were also inversely proportional to stimulus rate. However, only ICX units were inversely proportional to trial (i.e. as was the ASR). When response properties of individual units were examined, a variety of profiles was observed with regard to rate and trial sensitivity: units were either not sensitive to stimulus rate, inversely sensitive, directly sensitive, or complexly sensitive. Superimposed on these rate classifications were trial sensitivity, with some units being insensitive to trial, directly sensitive, or inversely sensitive. The incidence of response types differed in some respects between ICC and ICX and these differences were, in general, consistent with the mean responses of the neuronal populations.     

Lesions of the central gray block the sensitization of the acoustic startle response in rats

The amplitude of the acoustic startle response (ASR) in rats is increased after administration of footshocks, a phenomenon termed sensitization. The neural circuitry underlying this kind of modulation of the ASR is only partly understood. It has been shown that the central nucleus of the amygdala (cA) and its efferent pathway to the caudal pontine reticular nucleus (PnC), an essential part of the primary startle circuit, is important for the sensitization of the ASR [23]. It was unclear, however, whether the amygdaloreticular pathway directly transfers the effects of footshocks onto the PnC, or whether there exists a relay nucleus within this pathway. The present study tested the hypothesis that the midbrain central gray (CG) is important for the sensitization of the ASR. Neuroanatomical tracing experiments indicate that a descending projection from the medial part of the cA might form synapses in the region of the midbrain CG, where a descending projection to the PnC takes its origin. We lesioned the dorsal and lateral part of the CG with the neurotoxin quinolinic acid and measured the effects of this lesion on the sensitization of the ASR by footshocks. Lesions confined to the dorsal and lateral parts of the CG totally blocked the sensitization of the ASR, without affecting the ASR amplitude in the absence of sensitizing stimuli. These findings suggest a crucial role of the CG for the sensitization of the ASR. The present data are reconciled with other findings from our laboratory and from the literature and we discuss possible mechanisms underlying the mediation of the sensitization of the ASR in rats.     

Effects of (+)-methamphetamine on path integration and spatial learning,but not locomotor activity or acoustic startle,align with the stress hyporesponsive period in rats

Rats treated with (+)-methamphetamine (MA) on postnatal days (P) 11–20 exhibit long-term spatial and path integration (Morris water maze (MWM) and Cincinnati water maze (CWM)) learning deficits whereas those treated on P1–10 do not. MA treatment increases corticosterone release in an age-dependent U-shaped pattern that corresponds to the stress hyporesponsive period (SHRP; P4–15). Here we tested the hypothesis that the cognitive effects induced by MA are associated with treatment that begins within the SHRP. Three treatment regimens were compared, P1–10, P6–15, and P11–20. One male/female pair/litter received 0, 10, or 25 mg/kg MA/dose (four doses/day at 2 h intervals given s.c. with 19–21 litters/regimen). Locomotor activity and acoustic startle were tested as behaviors not predicted to be associated with the SHRP. Cincinnati and Morris water maze findings were consistent with the hypothesis in that MA-treated animals exposed from P6–15 or P11–20 showed impaired learning compared to those exposed from P1–10; however, on probe trials in the Morris water maze, MA-induced memory impairments were not regimen-specific and were contributed to by all treatment regimens. All MA treatment regimens induced reductions in locomotor activity and acoustic startle facilitation as expected. No differential effect on prepulse trials was seen suggesting no impairment in sensory gating. Cognitive deficits from neonatal MA treatment are associated with the SHRP and may be the product of hypothalamic–pituitary–adrenal (HPA) axis dysregulation during critical periods of brain development.     

Glycine receptors in the caudal pontine reticular formation: are they important for the inhibition of the acoustic startle response?

The present paper sought to test the hypothesis that inhibitory glycine receptors (GlyRs) on giant neurons of the caudal pontine reticular formation (PnC) are involved in the inhibition of the acoustic startle response (ASR) in rats. First we provided evidence for the presence of the strychnine-sensitive inhibitory GlyR on PnC neurons by immunocytochemical labeling using an antibody against the α₁ subunit of the GlyR. We then measured the ASR as well as two ASR inhibiting phenomena, short-term habituation and prepulse inhibition, after microinjections of the glycine antagonist strychnine (0, 5 or 10 nmol) or the glycine agonist β-alanine (0, 50 or 100 nmol) into the PnC. Neither strychnine nor β-alanine had a measurable influence on any of the parameters of the ASR investigated (amplitude, short-term habituation, prepulse inhibition). In contrast, systemic injection of strychnine (1 mg/kg) markedly increased the ASR amplitude. The systemic administration of strychnine did not impair prepulse inhibition. The human ‘startle disease’ (hyperekplexia), an exaggerated startle response, is caused by a defect of the α₁ subunit of the inhibitory GlyR, but it is unclear at which site in the central nervous system this defect ultimately leads to the symptoms of hyperekplexia. Our data indicate that a blockade of the inhibitory GlyRs in the PnC does not affect the ASR of rats, suggesting that deficient GlyRs in the PnC might not be involved in the etiology of the human ‘startle disease’. We conclude that the inhibitory GlyRs on PnC neurons are not necessary for the inhibition of the ASR and believe that they are involved in another behavioral context.     

Lesions of the nucleus basalis magnocellularis do not impair prepulse inhibition and latent inhibition of fear-potentiated startle in the rat

The present study tested if lesions of the nucleus basalis magnocellularis (NBM) affect prepulse inhibition (PPI) of the acoustic startle response and latent inhibition (LI) of fear-potentiated startle. The NBM is known to play an important role in learning and memory. Recently, the interest of research focused on its role in attentional and response selection processes. We here tested the effect of excitotoxic NBM-lesions on PPI, a phenomenon of sensorimotor gating that occurs at early stages of information processing. We also assessed the lesion effects on LI, a phenomenon of reduced conditioning after stimulus preexposure that can be used to measure selective attention. Bilateral infusions into the NBM of 80 nmol of quinolinic acid markedly reduced the number of choline acetyltransferase immunopositive neurons in the NBM and lead to a pronounced reduction of acetylcholine esterase in the cortex and the amygdala. However, no effects on PPI, fear-conditioning, or LI of fear-potentiated startle were found. Therefore, we conclude that there is no NBM-driven attentional or response selection process involved in PPI. Furthermore, the simple association learning in the classical conditioning paradigm used for fear-potentiated startle or LI is unaffected by NBM-lesions.     

A review of the effects of acute and chronic cannabinoid exposure on the stress response

While cannabis has been used for centuries for its stress-alleviating properties, the effects of acute and chronic cannabinoid exposure on responses to stress remain poorly understood. This review provides an overview of studies that measured stress-related endpoints following acute or chronic cannabinoid exposure in humans and animals. Acute cannabinoid exposure increases basal concentrations of stress hormones in rodents and humans and has dose-dependent effects on stress reactivity in humans and anxiety-like behavior in rodents. Chronic cannabis exposure is associated with dampened stress reactivity, a blunted cortisol awakening response (CAR), and flattened diurnal cortisol slope in humans. Sex differences in these effects remain underexamined, with limited evidence for sex differences in effects of cannabinoids on stress reactivity in rodents. Future research is needed to better understand sex differences in the effects of cannabis on the stress response, as well as downstream impacts on mental health and stress-related disorders.     

Men and women differ in inflammatory and neuroendocrine responses to endotoxin but not in the severity of sickness symptoms

Impaired mood and increased anxiety represent core symptoms of sickness behavior that are thought to be mediated by pro-inflammatory cytokines. Moreover, excessive inflammation seems to be implicated in the development of mood/affective disorders. Although women are known to mount stronger pro-inflammatory responses during infections and are at higher risk to develop depressive and anxiety disorders compared to men, experimental studies on sex differences in sickness symptoms are scarce. Thus, the present study aimed at comparing physiological and psychological responses to endotoxin administration between men and women. Twenty-eight healthy volunteers (14 men, 14 women) were intravenously injected with a low dose (0.4 ng/kg) of lipopolysaccharide (LPS) and plasma concentrations of cytokines and neuroendocrine factors as well as negative state emotions were measured before and until six hours after LPS administration. Women exhibited a more profound pro-inflammatory response with significantly higher increases in tumor necrosis factor (TNF)-α and interleukin (IL)-6. In contrast, the LPS-induced increase in anti-inflammatory IL-10 was significantly higher in men. The cytokine alterations were accompanied by changes in neuroendocrine factors known to be involved in inflammation regulation. Endotoxin injection induced a significant increase in noradrenaline, without evidence for sex differences. The LPS-induced increase in cortisol was significantly higher in woman, whereas changes in dehydroepiandrosterone were largely comparable. LPS administration also increased secretion of prolactin, but only in women. Despite these profound sex differences in inflammatory and neuroendocrine responses, men and women did not differ in endotoxin-induced alterations in mood and state anxiety or non-specific sickness symptoms. This suggests that compensatory mechanisms exist that counteract the more pronounced inflammatory response in women, preventing an exaggerated sickness response. Disturbance of these compensatory mechanisms by environmental factors such as stress may promote the development of affective disorders in women.     

Neonatal lesions of the ventral hippocampal formation disrupt neuroendocrine responses to auditory stress in the adult rat

Lesioning the ventral hippocampal formation (vHF) in the neonatal rat with an excitotoxin replicates several features of schizophrenia. Similar lesions in the adult rat disrupt the normal constraint of neuroendocrine responses to environmental stressors, which is of potential interest because the enhanced HPA axis and antidiuretic hormone activity in schizophrenia is linked to acute stress and hippocampal formation (HF) pathology. In the current study, we investigated the effects of neonatal ventral hippocampal formation lesions (NVHFL) on plasma adrenocorticotropin hormone (ACTH) and arginine vasopressin (AVP) responses following a 2-min acoustic stressor in the adult rat. Levels of the two hormones did not differ between SHAM-operated and NVHFL animals in their home cages. ACTH levels doubled in SHAM-operated animals immediately following stress, but increased more than six-fold in the NVHFL group. AVP levels were halved immediately following stress in SHAM-operated animals, but did not change significantly in NVHFL. Findings could not be attributed to intervening factors known to influence neuroendocrine activity. Thus, NVHFL appear to disrupt the HF-mediated constraint of neuroendocrine responses to stress, and model the neuroendocrine dysfunction seen in schizophrenia. We posit that clarification of how NVHFL alters relatively “simple”, well characterized, and phylogenetically preserved systems, such as the neuroendocrine system, may provide insight into the mechanism of hippocampal pathology in schizophrenia.     

Dopaminergic neuronal injury in the adult rat brain following neonatal exposure to lipopolysaccharide and the silent neurotoxicity

Our previous studies have shown that neonatal exposure to lipopolysaccharide (LPS) resulted in motor dysfunction and dopaminergic neuronal injury in the juvenile rat brain. To further examine whether neonatal LPS exposure has persisting effects in adult rats, motor behaviors were examined from postnatal day 7 (P7) to P70 and brain injury was determined in P70 rats following an intracerebral injection of LPS (1 mg/kg) in P5 Sprague-Dawley male rats. Although neonatal LPS exposure resulted in hyperactivity in locomotion and stereotyped tasks, and other disturbances of motor behaviors, the impaired motor functions were spontaneously recovered by P70. On the other hand, neonatal LPS-induced injury to the dopaminergic system such as the loss of dendrites and reduced tyrosine hydroxylase immunoreactivity in the substantia nigra persisted in P70 rats. Neonatal LPS exposure also resulted in sustained inflammatory responses in the P70 rat brain, as indicated by an increased number of activated microglia and elevation of interleukin-1β and interleukin-6 content in the rat brain. In addition, when challenged with methamphetamine (METH, 0.5 mg/kg) subcutaneously, rats with neonatal LPS exposure had significantly increased responses in METH-induced locomotion and stereotypy behaviors as compared to those without LPS exposure. These results indicate that although neonatal LPS-induced neurobehavioral impairment is spontaneously recoverable, the LPS exposure-induced persistent injury to the dopaminergic system and the chronic inflammation may represent the existence of silent neurotoxicity. Our data further suggest that the compromised dendritic mitochondrial function might contribute, at least partially, to the silent neurotoxicity.     

Converging influence of neonatal novelty experience and maternal self-stress regulation on the plasticity of offspring acoustic startle response latency

Behavioral and brain development is influenced by both maternal and non-maternal aspects of the postnatal environment and the precise nature of their interaction is the topic of an ongoing debate. Here, we consider the joint influence of neonatal environmental novelty and maternal self-stress regulation on the development of acoustic startle reflex (ASR), an extensively investigated model system for learning and neural plasticity. We test the hypothesis in the rat that brief repeated neonatal exposures to novelty can affect ASR in late adulthood and that this influence is sensitive to postnatal context of maternal self-stress regulation. We carried out the neonatal and early adulthood novelty exposure (PND 1-21 and PND 54-63 respectively), obtained measures of maternal self-stress regulation after weaning (PND 25-26), and evaluated in the male rats, ASR and ASR plasticity at adulthood (ASR1 and ASR2, one week apart, at 13.5 months of age). During ASR1, offspring, whose mothers had poor self-stress regulation as indexed by a high circulating basal corticosterone (CORT) concentration, showed a novelty-induced decrease of ASR latency. Offspring whose mothers had good self regulation as indexed by a low CORT, showed a novelty-induced increase in ASR latency. From ASR1 to ASR2, offspring whose mothers had poor self-stress regulation, showed a novelty-induced ASR latency habituation (increase in latency) while offspring whose mothers had good self regulation showed no novelty effect. These findings support a novel framework in which maternal and non-maternal postnatal environments exert interacting influences on the neonates, with maternal individual differences in self-stress regulation providing a critical context to enable bidirectional novelty-induced influence across different rat families.     

Effects of chronic stress and corticosterone on sialidase activity in the rat hippocampus

Sialidases are acid exoglycosidases that catalyse the removal of sialic acid from non-reducing end of sialoglucoconjugated substrates. Synaptic plasticity depends on sialylation state of proteins and lipids mediated by sialic acid-metabolizing enzymes. Since chronic stress causes both, hippocampal atrophy and impairment of learning, it is reasonable to investigate whether sialidase is implicated in these processes. In this study, we tested effects of chronic stress (immobilization, 2 h daily, 21 days) or chronic corticosterone administration (5 mg/kg, sc, daily) on sialidase activity and sialylated NCAMs expression in rat hippocampus.The results showed that chronic stress affects hippocampus-depended spatial learning in the Barnes maze. Both, stress (p > 0.05) and corticosterone (p < 0.001), increased latencies to enter the escape tunnel of the maze in comparison to control animals. Similar but not significant differences between control and other experimental groups were observed in the numbers of errors. Chronic stress (p > 0.05) and corticosterone (p < 0.05) decreased sialidase activity in the brain homogenates and synaptosomes (p < 0.05, both). In the stressed animals, these changes were related to significantly higher expression of polysialic acid. These results indicate that changes in sialidase activity caused by stress and chronic corticosterone administration reflect disturbances of polysialylated glycoconjugates known to be related to synaptic plasticity in hippocampus.