Changes in perceived ageism during the COVID-19 pandemic: impact on quality of life and mental well-being among Dutch adults aged 55 and older.

Objectives: The COVID-19 pandemic brought ageism to the forefront of public discourse. Negative ageism incurs more negative self-perceptions of aging, which affects physical and mental functioning. Whether negative ageism as perceived and experienced by older adults has worsened as the pandemic lingered, and how such changes impact quality of life (QoL) and mental well-being (MWB), remain urgent questions.Method: In a sample of adults aged 55 or older (n = 500), we aimed to address this by administering the Perceived Ageism Questionnaire twice during the pandemic (T1: between October 2020 and May 2021; T2: on average 45 wk after T1).Results: Higher levels of perceived negative ageism were associated with lower QoL and MWB, at least partially through its unfavorable effects on self-perceptions of aging, even after controlling for ageism experiences in the preceding year (at T2, corrected for T1). Furthermore, we found that perceived negative ageism increased from T1 to T2, which had negative implications for QoL/MWB. Opposite effects were found for perceived positive ageism, although less consistently.Conclusion: These patterns reveal that ageism as perceived and experienced by adults of 55 or older became stronger and more negative throughout the COVID-19 pandemic, which had detrimental implications for individuals' QoL and MWB. These disconcerting findings emphasize the importance of combatting negative ageism in our society.

The consequences of early-life adversity: neurobiological, behavioural and epigenetic adaptations.

During the perinatal period, the brain is particularly sensitive to remodelling by environmental factors. Adverse early-life experiences, such as stress exposure or suboptimal maternal care, can have long-lasting detrimental consequences for an individual. This phenomenon is often referred to as 'early-life programming' and is associated with an increased risk of disease. Typically, rodents exposed to prenatal stress or postnatal maternal deprivation display enhanced neuroendocrine responses to stress, increased levels of anxiety and depressive-like behaviours, and cognitive impairments. Some of the phenotypes observed in these models of early-life adversity are likely to share common neurobiological mechanisms. For example, there is evidence for impaired glucocorticoid negative-feedback control of the hypothalamic-pituitary-adrenal axis, altered glutamate neurotransmission and reduced hippocampal neurogenesis in both prenatally stressed rats and rats that experienced deficient maternal care. The possible mechanisms through which maternal stress during pregnancy may be transmitted to the offspring are reviewed, with special consideration given to altered maternal behaviour postpartum. We also discuss what is known about the neurobiological and epigenetic mechanisms that underpin early-life programming of the neonatal brain in the first generation and subsequent generations, with a view to abrogating programming effects and potentially identifying new therapeutic targets for the treatment of stress-related disorders and cognitive impairment.

Distribution of the glucocorticoid receptor in the human amygdala; changes in mood disorder patients.

Exposure to stress activates the hypothalamic-pituitary-adrenal (HPA) axis that stimulates glucocorticoid (GC) release from the adrenal. These hormones exert numerous effects in the body and brain and bind to a.o. glucocorticoid receptors (GR) expressed in the limbic system, including the hippocampus and amygdala. Hyperactivity of the HPA axis and disturbed stress feedback are common features in major depression. GR protein is present in the human hypothalamus and hippocampus, but little is known-neither in healthy subjects nor in depressed patients-about GR expression in the amygdala, a brain structure involved in fear and anxiety. Since chronic stress in rodents affects GR expression in the amygdala, altered GR protein level in depressed versus healthy controls can be expected. To test this, we investigated GR-α protein expression in the post-mortem human amygdala and assessed changes in ten major or bipolar depressed patients and eight non-depressed controls. Abundant GR immunoreactivity was observed in the human amygdala, both in neurons and astrocytes, with a similar pattern in its different anatomical subnuclei. In major depression, GR protein level as well as the percentage of GR-containing astrocytes was significantly higher than in bipolar depressed patients or in control subjects. Taken together, the prominent expression of GR protein in the human amygdala indicates that this region can form an important target for corticosteroids and stress, while the increased GR expression in major, but not bipolar, depression suggests possible involvement in the etiology of major depression.

Stress and excitatory synapses: from health to disease.

Individuals are exposed to stressful events in their daily life. The effects of stress on brain function ranges from highly adaptive to increasing the risk to develop psychopathology. For example, stressful experiences are remembered well which can be seen as a highly appropriate behavioral adaptation. On the other hand, stress is an important risk factor, in susceptible individuals, for depression and anxiety. An important question that remains to be addressed is how stress regulates brain function and what determines the threshold between adaptive and maladaptive responses. Excitatory synapses play a crucial role in synaptic transmission, synaptic plasticity and behavioral adaptation. In this review we discuss how brief and prolonged exposure to stress, in adulthood and early life, regulate the function of these synapses, and how these effects may contribute to behavioral adaptation and psychopathology.

Within-litter variation in maternal care received by individual pups correlates with adolescent social play behavior in male rats.

Maternal care represents an essential environmental factor during the first post-natal week(s) of rodents and is known to have lasting consequences for neuronal structure, brain function as well as behavioral outcome later in life, including social functions and reward-related processes. Previous experiments have shown that the amount of maternal care received by individual pups varies substantially, even within one litter. During adolescence, mammals display high levels of social play behavior, a rewarding form of social interaction that is of great importance for social and cognitive development. In order to investigate how maternal care influences adaptive social behavior later in life, we here examined whether individual differences in maternal licking and grooming (%LG) received during the first postnatal week affect social play behavior during adolescence. We observed that %LG received by male rats early in life correlates positively with the frequency and duration of pouncing and pinning, the two most characteristic behavioral expressions of social play behavior in rats. The latency to engage in social exploration also correlated with %LG. In female rats we observed no correlation between %LG and any social parameter. The data indicate that subtle variations in maternal care received early in life influence social interactions in male adolescent rats. These changes in social play likely have repercussions for the social development of male rats, suggesting that maternal care can have both direct and indirect effects on the behavioral development of the offspring.

Maternal care received by individual pups correlates with adult CA1 dendritic morphology and synaptic plasticity in a sex-dependent manner.

Maternal care is an important environmental factor for rats early in life. Adult offspring from dams exhibiting extremely high versus low maternal care differ remarkably in dendritic complexity and long-term synaptic potentiation in the CA1 area. However, >70% of the pups do not belong to these extreme categories of maternal care, questioning the general relevance of these observations. Therefore, the present study investigated whether the influence of maternal care is discernable over its entire range and can serve as an index predicting later CA1 structure and function. The amount of licking and grooming (%LG) received was determined for each pup during the first postnatal week. In males, both total apical branch length and dendritic complexity correlated significantly and positively with %LG. In females, we observed a nonsignificant negative correlation, also when controlled for variations in oestradiol and progesterone levels. The correlation in females was significantly different from that in males. No significant correlation was observed between the %LG and the amount of synaptic potentiation, either in male or in female offspring, regardless of whether slices had been treated with corticosterone or vehicle. However, in male rats, the degree of potentiation seen after corticosterone compared to vehicle treatment was almost significantly related to the %LG received early in life; this differed significantly from that observed in females. The data from the present study suggest that %LG received early in life results in mild, yet sex-dependent effects on adult CA1 structure and function.

Early-life stress mediated modulation of adult neurogenesis and behavior.

Early life is a period of unique sensitivity during which experience can confer enduring effects on brain structure and function. During early perinatal life the quality of the surrounding environment and experiences, in particular the parent-child relationship, is associated with emotional and cognitive development later in life. For instance, adverse early-life experience is correlated with an increased vulnerability to develop psychopathologies and aging-related cognitive decline. These are thought to be mediated by acute and long-lasting effects on the, at that time still developing, stress-neuroendocrine and cognitive systems. Adult hippocampal neurogenesis is involved in learning and memory while both regulation of the stress response as well as early-life stress is known to permanently reduce neurogenesis, and to be implicated in these functional deficits. In order to increase our understanding of the influence of the perinatal environment on the long-lasting programming of neurogenesis, we here discuss immediate and lasting effects of various adverse early-life experiences on hippocampal neurogenesis and the associated behavioral alterations. Considering the persistence of these effects, the underlying molecular mechanisms, with focus on the potential epigenetic mechanisms will be discussed as well. Finally, special attention will be paid to the prominent sex differences in early-life stress-induced alterations in neurogenesis.

Opposite effects of glucocorticoid receptor activation on hippocampal CA1 dendritic complexity in chronically stressed and handled animals.

Remodeling of synaptic networks is believed to contribute to synaptic plasticity and long-term memory performance, both of which are modulated by chronic stress. We here examined whether chronic stress modulates dendritic complexity of hippocampal CA1 pyramidal cells, under conditions of basal as well as elevated corticosteroid hormone levels. Slices were prepared from naïve, handled or chronically stressed animals and briefly treated with vehicle or corticosterone (100 nM); neurons were visualized with a fluorescent dye injected into individual CA1 pyramidal cells. We observed that 21 days of unpredictable stress did not affect hippocampal CA1 apical or basal dendritic morphology compared with naïve animals when corticosteroid levels were low. Only when slices from stressed animals were also exposed to elevated corticosteroid levels, a significant reduction in apical (but not basal) dendritic length became apparent. Unexpectedly, animals that were handled or 3 weeks showed a reduction in both apical dendritic length and number of apical branch points when compared with naïve animals. Apical dendritic length and number of branch points were restored to levels found in naïve animals several hours after in vitro treatment with 100 nM corticosterone. All effects of acute corticosterone administration could be prevented by the glucocorticoid receptor antagonist RU38486 given during the last 4 days of the stress or handling protocol. We conclude that brief exposure to high concentrations of corticosterone can differently affect apical dendritic structure, depending on the earlier history of the animal, a process that critically depends on involvement of the glucocorticoid receptor.

Dissociation between apoptosis, neurogenesis, and synaptic potentiation in the dentate gyrus of adrenalectomized rats.

Removal of adrenal hormone corticosterone in rats aged 3-4 months results within 3 days in acceleration of apoptosis and proliferation of newborn cells in the dentate gyrus (DG). A critical question is whether such a shift in the maturity of dentate cells after adrenalectomy (ADX) affects synaptic plasticity. To address this question, male rats were adrenalectomized and synaptic potentiation was recorded in vitro in hippocampal slices, as well as in vivo, in response to high frequency stimulation of the perforant path, 3 days after ADX. At this time-point, cell loss was assessed and proliferation was examined. Based on two independent parameters, bromodeoxyuridine and Ki-67, we found that removal of the adrenal glands increases proliferation rate. This increase in proliferation was, in particular, evident in those animals that displayed substantial cell loss. The accelerated cell-turnover after ADX was accompanied by reduced synaptic potentiation, both when recorded in vitro and in vivo. Corticosterone replacement in vivo (in adrenalectomized animals), at levels that activate the mineralocorticoid receptor, prevented ADX-induced proliferation, apoptosis, and restored synaptic potentiation to control levels. Importantly, corticosterone applied to slices from adrenalectomized rats also normalized synaptic potentiation, despite increased proliferation. This suggests that changes in cell proliferation and apoptotic cell death in the DG are not necessarily key factors determining the efficacy of synaptic potentiation.

Blockade of glucocorticoid receptors rapidly restores hippocampal CA1 synaptic plasticity after exposure to chronic stress.

Prolonged exposure to stressful events has been reported to inhibit the ability of hippocampal synapses to increase their synaptic efficacy. Here we tested if these effects could be prevented by blocking activation of glucocorticoid receptors during the last 4 days of the stress paradigm. In order to address this question, animals were exposed to 21 days of variable and inescapable stressors. Handled animals served as controls. During the last 4 days of the stress regime, animals were treated with the glucocorticoid receptor antagonist RU486. We found that 1 day after the last stressor, synaptic plasticity in the CA1 area of hippocampal slices is impaired in chronically stressed animals. Importantly, treating chronically stressed animals with RU486 for 4 days completely prevented this decrease in synaptic potentiation; RU486 treatment of handled controls did not affect potentiation. Treating hippocampal slices from control animals with high levels of corticosterone also impaired synaptic plasticity; this effect was similar for untreated and RU486-treated animals. Treating slices from chronically stressed animals with corticosterone did not further decrease synaptic plasticity. These data indicate that 4 days blockade of the glucocorticoid receptor, during a stress regime, is sufficient to fully restore synaptic plasticity.

Glucocorticoid receptor activation selectively hampers N-methyl-D-aspartate receptor dependent hippocampal synaptic plasticity in vitro.

Corticosterone and exposure to stressful experiences have been reported to decrease hippocampal synaptic plasticity, in particular when relatively mild stimulation paradigms-presumably activating predominantly N-methyl-d-aspartate receptors-are being used. Using various stimulation paradigms and pharmacological approaches we tested therefore the hypothesis that elevated corticosterone levels, by activating glucocorticoid receptors, predominantly hamper N-methyl-D-aspartate receptor dependent synaptic plasticity in vitro. To address this, mouse hippocampal slices were treated for 20 min with corticosterone (100 nM) or vehicle and synaptic efficacy was examined 1-6 h later. First, we found that primed burst potentiation and synaptic potentiation after 10 Hz stimulation are predominantly N-methyl-D-aspartate receptor dependent, and are significantly suppressed after corticosterone treatment. Second, these latter effects were prevented by treating slices with the glucocorticoid receptor antagonist mifepristone prior to and during corticosterone administration. Third, theta burst potentiation, which was shown to involve activation of both N-methyl-D-aspartate receptors, voltage-dependent calcium channels and possibly other mechanisms, was not affected by corticosterone. However, theta-burst potentiation in the presence of nifedipine-singling out primarily the N-methyl-D-aspartate receptor dependent component-was reduced by corticosterone. These results indicate that corticosterone, via glucocorticoid receptor activation, selectively hampers N-methyl-D-aspartate receptor dependent synaptic plasticity in vitro and leaves more complex forms of long term potentiation unaffected. We speculate that these effects are involved in the impairment of cognitive performance by corticosteroid hormones after exposure to stressful and traumatic experiences.

Corticosterone and stress reduce synaptic potentiation in mouse hippocampal slices with mild stimulation.

Elevation of circulating corticosterone levels, either through exogenous administration of the hormone or following stress exposure, is known to reduce hippocampal synaptic potentiation in rodents. It is presently debated whether this reduction is due to activation of hippocampal glucocorticoid receptors or is primarily caused in other brain structures projecting to the hippocampus. To address this issue, we examined whether synaptic potentiation in hippocampal slices from mice with low basal corticosterone levels was altered 1-4 h after a brief in vitro administration of 100 nM corticosterone. Population spike and field excitatory postsynaptic potential (fEPSP) were recorded in the cell and dendritic layers, respectively, of the CA1 area, in response to Schaffer collateral/commissural fiber stimulation. Basal characteristics of the stimulus-response relationship were not affected by corticosterone treatment, except that after corticosterone treatment the maximal fEPSP slope was reduced while the excitability ratio was increased. For studies on potentiation of the fEPSP and population spike, stimulus intensities were chosen to evoke half maximal responses before potentiation; this intensity was significantly lower for the fEPSP than for the population spike. Primed burst potentiation of the fEPSP but not population spike was significantly attenuated after corticosterone treatment. When using a more rigorous stimulation paradigm, i.e. theta burst potentiation, synaptic potentiation was not affected by corticosterone. Raising corticosterone levels in mice by exposure to a psychosocial stressor led to comparable results in subsequent in vitro experiments; stress reduced primed burst potentiation only of the fEPSP. These data support that corticosterone affects synaptic potentiation in the mouse via direct activation of hippocampal glucocorticoid receptors but only when using mild stimulation conditions.

The corticosterone synthesis inhibitor metyrapone prevents hypoxia/ischemia-induced loss of synaptic function in the rat hippocampus.

BACKGROUND AND PURPOSE: Ischemia is accompanied by abundant corticosterone secretion, which could potentially exacerbate brain damage via activation of glucocorticoid receptors. We addressed whether manipulating steroid levels during ischemia affects hippocampal synaptic function along with neuronal structure. Moreover, we established whether pretreatment with the glucocorticoid receptor antagonist RU38486 is as effective in preventing deleterious effects after ischemia as is the steroid synthesis inhibitor metyrapone. METHODS: Rats underwent 20 minutes of unilateral hypoxia/ischemia (HI). Convulsions were monitored after HI, and 24 hours later, field potentials were recorded in vitro in the hippocampal CA1 area in response to stimulation of the Schaffer collateral/commissural fibers. Morphological alterations were determined in brain slices from the same animals. Data were correlated with steroid treatment before HI. RESULTS: Metyrapone suppressed plasma corticosteroid levels during HI, whereas corticosterone treatment significantly elevated plasma steroid levels. These treatments affected the incidence of visible seizures after HI: corticosterone treatment resulted in the highest incidence, whereas metyrapone attenuated the occurrence of seizures. Moreover, the HI-induced impairment in synaptic transmission in the CA1 area in vitro was exacerbated by concomitant corticosteroid treatment and alleviated by pretreatment with metyrapone. In parallel, degenerative changes in the hippocampus after HI were most pronounced after corticosterone treatment, whereas metyrapone reduced these alterations. RU38486 was effective only in reducing the incidence of seizures shortly after ischemia. CONCLUSIONS: We tentatively conclude that synaptic function along with cellular integrity is preserved after HI by preventing the ischemia-evoked rise in corticosteroid levels rather than blocking the glucocorticoid receptor.

Postischemic steroid modulation: effects on hippocampal neuronal integrity and synaptic plasticity.

Elimination of corticosteroids after ischemia, by removal of the adrenals, has been reported to preserve neuronal integrity later. To establish the therapeutic potential of this observation, the authors address two questions: first, whether clinically more relevant steroid manipulations after ischemia exert similar protective effects, and second, whether changes in synaptic functioning occur along with structural alterations. To test this, the authors treated animals immediately after hypoxia-ischemia with (1) the steroid synthesis inhibitor metyrapone, (2) the synthetic glucocorticoid receptor agonist dexamethasone, (3) the selective glucocorticoid antagonist RU 38486, or (4) corticosterone. Metyrapone, but none of the other compounds, attenuated the occurrence of seizures immediately after ischemia. Twenty-four hours after hypoxia-ischemia, CAI hippocampal field potentials in response to stimulation of Schaffer/commissural fibers were found to be reduced. The attenuation of synaptic transmission was partly prevented by metyrapone. None of the other experimental treatments influenced the impaired synaptic function. Gross morphologic analysis revealed no differences in the loss of neuronal structure between the experimental groups at this time point. Taken together, these data suggest that metyrapone preserves neuronal functioning despite loss of neuronal structure. The authors tentatively conclude that preventing the ongoing production of steroids shortly after ischemia can delay and attenuate the appearance of ischemia-related pathology.

Metyrapone reduces rat brain damage and seizures after hypoxia-ischemia: an effect independent of modulation of plasma corticosterone levels?

Hypoxia-ischemia is accompanied by abundant corticosterone secretion that could exacerbate brain damage after the insult. The authors demonstrate that the steroid synthesis inhibitor metyrapone (150 mg/kg subcutaneously) suppresses the hypoxia-ischemia-induced rise of plasma corticosterone levels (17.3 +/- 3.6 micrograms/dL) when compared with corticosterone-treated animals (72.2 +/- 4.8 micrograms/dL) immediately after hypoxia-ischemia. In parallel, metyrapone reduced brain damage (P < 0.05). Moreover, none of the metyrapone-treated animals displayed seizures, whereas seven of eight corticosterone-treated animals had seizures after hypoxia-ischemia. Although corticosterone administration in metyrapone-treated animals elevated plasma corticosterone levels (39.0 +/- 5.3 micrograms/dL), this did not result in a subsequent increase in brain damage and seizures when compared with metyrapone-treated animals. The authors conclude that metyrapone reduces brain damage and the incidence of seizures after hypoxia-ischemia but that this effect might partially be independent from its effect on modulating plasma corticosterone levels.

Altered expression of the cell cycle regulatory protein cyclin D1 in the rat dentate gyrus after adrenalectomy-induced granular cell loss.

The loss of dentate gyrus (DG) granular cells after removal of the rat adrenal glands (ADX) is mediated by a process that is apoptotic in nature. The present study was initiated to compare changes in the immunocytochemical distribution of the cell-cycle regulatory protein cyclin D1, which has been implicated in apoptosis, with the loss of DG granular cells after ADX. Our data indicate that cyclin D1-immunoreactivity (cyclin D1-ir) is enhanced in the rat dentate gyrus after adrenalectomy. The enhanced cyclin D1-ir shows a close relationship, both in time and space, with granular cell loss in the rat dentate gyrus that occurs after adrenalectomy. However, the enhanced cyclin D1-immunoreactivity was present in microglia and radial glia rather than in the dentate gyrus granular cells. This suggests that cyclin D1 is not directly involved in apoptosis of granular cells in the rat dentate gyrus after adrenalectomy.

Altered synaptic plasticity in hippocampal CA1 area of apolipoprotein E deficient mice.

In mice with a homozygous or heterozygous deficiency for ApoE as well as in wild-type animals we established synaptic responsiveness in the hippocampal CA1 area following stimulation of the Schaffer/commissural fibers. The maximal population spike amplitude was significantly larger in wild-type animals than in mice lacking the ApoE gene, whereas the facilitation in population spike amplitude after paired pulse stimulation was most pronounced in homozygous mutant mice. Primed burst stimulation induced a lasting increase in population spike amplitude of all three groups. Apart from a more pronounced initial potentiation in the homozygous mutants, primed burst potentiation was comparable in all groups. Subsequent theta burst stimulation resulted in a long-term enhanced synaptic responsiveness which was impaired in heterozygous animals. The data show that both homo- and heterozygous ApoE mutant mice display altered synaptic plasticity in the hippocampal CA1 area.

Exposure to chronic psychosocial stress and corticosterone in the rat: effects on spatial discrimination learning and hippocampal protein kinase Cgamma immunoreactivity.

Previous reports have demonstrated a striking increase of the immunoreactivity of the gamma-isoform of protein kinase C (PKCgamma-ir) in Ammon's horn and dentate gyrus (DG) of rodent hippocampus after training in a spatial orientation task. In the present study, we investigated how 8 days of psychosocial stress affects spatial discrimination learning in a hole board and influences PKCgamma-ir in the hippocampal formation. The acquisition of both reference memory and working memory was significantly delayed in the stressed animals during the entire training period. With respect to cellular plasticity, the training experience in both nonstressed and stressed groups yielded enhanced PKCgamma-ir in the CA1 and CA3 regions of the posterior hippocampus but not in subfields of the anterior hippocampus. Stress enhanced PKCgamma-ir in the DG and CA3 pyramidal cells of the anterior hippocampus. In stressed animals that were subsequently trained, the PKCgamma-ir was increased in the posterior CA1 region to the same level as that found in nonstressed trained animals. Stress apparently abrogated the PKCgamma-ir training response in the CA3 region. In a second experiment, the elevation of plasma corticosterone levels to values that are found during stress did not significantly influence reference memory scores but slightly and temporarily affected working memory. The training-induced enhancement of PKCgamma-ir in the CA1 region was similar in trained and corticosterone-treated trained animals, but the learning-induced PKCgamma-ir response in the posterior CA3 area was absent after corticosterone pretreatment. These results reveal that prolonged psychosocial stress causes spatial learning deficits, whereas artificial elevation of corticosterone levels to the levels that occur during stress only mildly affects spatial memory performance. The spatial learning deficits following stress are reflected only in part in the redistribution of hippocampal PKCgamma-ir following training.

Prolonged subordination stress increases Calbindin-D28k immunoreactivity in the rat hippocampal CA1 area.

Previously we observed that corticosteroids alter Calbindin-D28k immunoreactivity in the rat hippocampus. In the present study we investigated whether prolonged subordination stress, presumably producing elevated plasma corticosterone levels (1) altered the immunocytochemical distribution of the Ca(2+)-binding proteins Calbindin-D28k (CBir) and Parvalbumin (PVir) in the rat hippocampus, and (2) induced ongoing neurodegenerative changes using a silver impregnation method. Eight days of subordination stress reduced body weight, increased adrenal weight corrected for body weight and reduced thymus weight, indicating its effectiveness to produce a stressful situation. Stress increased CBir selectively in the CA1 pyramidal cell layer whereas PVir was not altered. Silver-impregnation revealed no ongoing neurodegenerative changes in any of the hippocampal subfields.

Region-specific alterations of calbindin-D28k immunoreactivity in the rat hippocampus following adrenalectomy and corticosterone treatment.

The aim of this study was (i) to compare the immunocytochemical distribution of the calcium-binding protein calbindin-D28k (CB) in the hippocampus of rats with the pattern of neurodegeneration following adrenalectomy (ADX) using silver impregnation, and (ii) to investigate the CB-immunoreactivity in the hippocampus following 3 weeks corticosterone treatment. 24 h following ADX no degenerative changes, nor alterations in CB-immunoreactivity were found in the hippocampus. Both 3 and 21 days following ADX neurodegeneration in the dentate gyrus could be observed which was accompanied with a loss of CB-immunoreactive (CB-ir) cells in that parts of the dentate gyrus suffering neuronal degeneration. Additionally we observed a marked loss of CB-ir in the CA1 area both 3 and 21 days following ADX. Three weeks daily corticosterone treatment (10 mg/day) induced a marked increase of CB-ir exclusively in the CA1 pyramidal cell layer. We conclude that (i) there is a close relationship between the loss of CB-immunoreactive cells in the DG and the neuronal degeneration in the dentate gyrus following ADX, and (ii) corticosterone appears to be involved in the regulation of calbindin-D28k in the CA1 pyramidal cell layer.