Edward
Member
- Joined
- Apr 20, 2013
- Messages
- 134
- Age
- 41
Put it all together and what do you get? A mechanism for why modern society is damaging to the thyroid... and if you use your imagination a bit... a mechanism for various different psychological behaviors...
Cerebellar brain volume accounts for variance in cognitive performance in older adults
http://www.ncbi.nlm.nih.gov/pubmed/20167312
Cognitive and motor function and the size of the cerebellum in adolescents born very pre-term
http://brain.oxfordjournals.org/content/124/1/60.full.pdf
Thyroid hormones, brain function and cognition: a brief review.
http://www.ncbi.nlm.nih.gov/pubmed/11835983
In addition to their role in cellular metabolic activity, thyroid hormones (THs), also regulate neural development; the central nervous system is particularly dependent on TH for normal maturation and function. Specifically, there appears to be extensive inter-reliance between TH and acetylcholine (Ach), nerve growth factor and hippocampal function. These associations led us to investigate the possible effects of thyroxine (L-T4) on performance of a spatial learning task, where cholinergic activity and hippocampal function are known to be important. Groups of rats (n=20) received saline (controls) or L-T4 at 2.5 or 5mg/kg daily for 4 days as a sub-chronic treatment, or 0, 5 or 10mg/kg doses administered every third day for 28 days prior to testing as a chronic regimen. Rats were assessed in a water maze for their ability to find a submerged or visible platform. Forty minutes prior to water maze testing, half the animals in each group received 1mg/kg scopolamine to elicit a cognitive deficit. Following testing, rats were decapitated, blood samples taken, and the frontal cortex and hippocampus were dissected out for acetylcholinesterase (AChE) assay. The results showed that L-T4 treatment, administered both sub-chronically and chronically, significantly enhanced the ability of rats to learn a spatial memory task, compared with controls. Moreover, both short-term and long-term L-T4 treatment reduced the cognitive-impairing effects of scopolamine. Improvements in performance were shown to occur alongside significantly increased cholinergic activity in frontal cortex and in the hippocampus of treated animals. These findings demonstrate an augmentative effect of L-T4 upon cognitive function, possibly mediated by an enhancement of cholinergic activity. The results support previous findings of a relationship between L-T4 and acetylcholine, and underscore possible mechanisms by which disorders of thyroid function may be associated with cognitive decline.
Maternal stress produces learning deficits associated with impairment of NMDA receptor-mediated synaptic plasticity.
http://www.ncbi.nlm.nih.gov/pubmed/16554481
Stress in adulthood can have a profound effect on physiology and behavior, but the extent to which prolonged maternal stress affects the brain function of offspring when they are adult remains primarily unknown. In the present work, chronic immobilization stress to pregnant mice affected fetal growth and development. When pups born from stressed mice were reared to adulthood in an environment identical to that of nonstressed controls, several physiological parameters were essentially unaltered. However, spatial learning and memory was significantly impaired in the maternally stressed offspring in adulthood. Furthermore, electrophysiological examination revealed a significant reduction in NMDA receptor-mediated long-term potentiation in the CA1 area of hippocampal slices. Subsequent biochemical analysis demonstrated a substantial decrease in NR1 and NR2B subunits of the NMDA receptor in synapses of the hippocampus, and the interaction between these two subunits appeared to be reduced. These results suggest that prolonged maternal stress leads to long-lasting malfunction of the hippocampus, which extends to and is manifested in adulthood.
Thyroid hormone and central nervous system development
http://joe.endocrinology-journals.org/content/165/1/1.full.pdf
It is well established that the thyroid status of neonates and children has a significant long-term impact on their behaviour, locomotor ability, speech, hearing and cognition (Legrand 1986). Delay in restoring normal thyroid status in the neonate can lead to irreversible damage. Prompt thyroid supplementation following the diagnosis of neonatal hypothyroidism can restore neurodevelopment to within the normal range (Fisher 1979). Even so, there are still subtle abnormalities of language, visuo-spatial impairments and lower mean IQs later in childhood compared with euthyroid controls. This implies that brain development may, in part, be thyroid hormone sensitive not only in the neonatal period but also prior to birth (New England Congenital Collaborative 1990, Heyerdahl 1991). Development of different areas of central nervous sytem has been associated with the timing and duration of thyroid hormone deficiency, suggesting that there are critical periods during which various parts of the brain are sensitive to thyroid hormone supply (Rovet et al. 1992).
Transient stimulation of myelin basic protein gene expression in differentiating cultured oligodendrocytes: a model for 3,5,3'-triiodothyronine-induced brain development.
http://www.ncbi.nlm.nih.gov/pubmed/9002997
We compared the regulation of myelin basic protein (MBP) gene expression by T3 in differentiating oligodendrocytes in culture with that previously observed by us in the neonatal rat brain. As in intact brain, expression of the T3R alpha gene preceded that of the T3R beta gene. Although the absence of T3 retarded the rate of accumulation of MBP messenger RNA, the level ultimately attained was similar to that reached in the presence of T3. This relationship mirrored the pattern observed in the neonatal brain. Transient transfection experiments showed that T3 regulates MBP expression at the transcriptional level, but only for a limited period during differentiation. These observations imply that the early rise of MBP messenger RNA is T3 dependent, whereas the terminal levels are maintained independently of T3. Both the T3-dependent and, surprisingly, the T3-independent expression of MBP require the presence of an intact T3 response element. T3 receptor may regulate MBP expression in a ligand-independent manner, or a nuclear factor other than T3 receptor may bind to the T3 response element of MBP to regulate terminal gene expression. These findings support the use of differentiating oligodendrocytes as a model of T3-induced brain development.
Prevalence of thyroid disorders in untreated adult celiac disease patients and effect of gluten withdrawal: an Italian multicenter study.
http://www.ncbi.nlm.nih.gov/pubmed/11280546
Thyroid disease was 3-fold higher in patients than in controls (p < 0.0005). Hypothyroidism, diagnosed in 31 patients (12.9%) and nine controls (4.2%), was subclinical in 29 patients and of nonautoimmune origin in 21. There was no difference regarding hyperthyroidism, whereas autoimmune thyroid disease with euthyroidism was present in 39 patients (16.2%) and eight controls (3.8%). In most patients who strictly followed a 1-yr gluten withdrawal (as confirmed by intestinal mucosa recovery), there was a normalization of subclinical hypothyroidism. Twenty-five percent of patients with euthyroid autoimmune disease shifted toward either a subclinical hyperthyroidism or subclinical hypothyroidism; in these subjects, dietary compliance was poor. In addition, 5.5% of patients whose thyroid function was normal while untreated developed some degree of thyroid dysfunction 1 yr later.
Maternal thyroid hormones early in pregnancy and fetal brain development
http://www.bprcem.com/article/S1521-690X(04)00022-3/abstract
During the last few decades our understanding of the possible role of thyroid hormones during brain development has increased and contributed to resolve previously discordant hypotheses, although much remains to be clarified. Thyroid hormones of maternal origin are present in the fetal compartment, despite the very efficient uterine-placental ‘barrier’, necessary to avoid potentially toxic concentrations of free T4 and T3 from reaching fetal tissues before they are required for development. T3 remains low throughout pregnancy, whereas FT4 in fetal fluids increases rapidly to adult levels, and is determined by the maternal availability of T4. It is present in embryonic fluids 4 weeks after conception, with FT4 steadily increasing to biologically relevant values. T3, generated from T4 in the cerebral cortex, reaches adult values by mid-gestation and is partly bound to specific nuclear receptor isoforms. Iodothyronine deioidinases are important for the spatial and temporal regulation of T3 bioavailability, tailored to the differing and changing requirements of thyroid hormone-sensitive genes in different brain structures, but other regulatory mechanism(s) are likely to be involved. Maternal transfer constitutes a major fraction of fetal serum T4, even after onset of fetal thyroid secretion, and continues to have an important protective role in fetal neurodevelopment until birth.
Prompt treatment of maternal hypothyroidism, identified by increased TSH, is being advocated to mitigate a negative effect on the woman and her child. However, even a moderate transient period of maternal hypothyroxinemia at the beginning of rat neurogenesis disrupts neuronal migration into cortical layers. These findings reinforce the epidemiological evidence that early maternal hypothyroxinemia—when neuronal migratory waves are starting—is potentially damaging for the child. Detection of an inappropiate first trimester FT4 surge that may not result in increased TSH, may be crucial for the prevention of learning disabilities in a significant number of unborn children.
Role of thyroid hormone during early brain development
http://www.eje.org/content/151/Suppl_3/U25.short
Socio-spatial criteria are important for the establishment of maternal preference in lambs
http://www.journals.elsevierhealth.com/periodicals/applan/article/S0168-1591(05)00220-0/abstract
At lambing, ewes (Ovis aries) tend to isolate themselves from the flock and this is believed to be beneficial to the early relationship with their young. Later, they return to the flock and lambs progressively interact with other conspecifics. This study focused on the importance of isolation and socio-spatial factors on maternal recognition in lambs. All the ewes gave birth in individual 2m2 pens and lambs were able to interact freely with their mothers. A first experiment investigated the role of isolation: INT1 lambs could progressively interact with other mothers and young in a pen which was increased in surface area from birth to 24h (0–6h: 1 ewe, 1 litter, 2m2; 6–12h: 2 ewes, 2 litters, 4m2; 12–24h: 4 ewes, 4 litters, 8m2); ISO lambs remained in small pens (2m2) and only with their mothers for 24h. The lambs were submitted to a 5min choice test between their own mothers and an alien ewe. At 12h INT1 lambs, unlike ISO lambs, showed a clear preference for their mothers. ISO lambs still did not show any maternal preference at 24h. The second experiment investigated the relative importance of social interactions while keeping the same space allowance for the two groups: INT2 lambs as described for INT1 in Experiment 1, and SPA lambs that remained isolated from the flock with their mothers but had the same increase in pen surface area as INT2 lambs. Both INT2 and SPA lambs displayed a preference for their own mothers at 12h but INT2 lambs did so more rapidly. Our data also suggest that INT1 and INT2 lambs chose their own mothers at a distance. These results demonstrate that progressively increasing social interactions with flock members other than the mother facilitates the establishment of a preference for the mother in lambs. Increasing space allowance only also seems to have facilitating effects. This suggests that a rich socio-spatial environment from birth has beneficial effects on the development of filial bonding.
Prenatal stress and cognitive development and temperament in infants
http://www.neurobiologyofaging.org/article/S0197-4580(03)00050-2/abstract
Studies in rodents and nonhuman primates indicate that maternal stress during pregnancy can influence the developing fetus, resulting in delay of motor and cognitive development and impaired adaptation to stressful situations. These effects may be mediated by the hypothalamic–pituitary–adrenal (HPA) axis. We examined whether stress during pregnancy predicted developmental outcome of human infants in a prospective design. Self-report data about daily hassles and pregnancy-specific anxiety and salivary cortisol levels were collected in nulliparous pregnant women. Dependent measures were scores on the Bayley Scales of Infant Development and on temperamental questionnaires at 3 and 8 months. Pregnancy-specific anxiety in mid pregnancy predicted lower mental and motor developmental scores at 8 months. Early morning values of cortisol in late pregnancy were negatively related to both mental and motor development at 3 months and motor development at 8 months. Pregnancy-specific anxiety explained 7% of the variance of test-affectivity and goal-directedness at 8 months. Increased maternal stress during pregnancy seems to be one of the determinants of temperamental variation and delay of development of infants and may be a risk factor for developing psychopathology later in life.
Prenatal Restraint Stress and Long-Term Affective Consequences
http://www.karger.com/Article/FullText/86711
Chronic or repeated stress during critical periods of human fetal brain development has been associated with various learning, behavioral and/or mood disorders in later life. In this investigation, pregnant Fischer 344 rats was individually restrained three times a day for 45 min during the last week of gestation in transparent plastic cylinders while at the same time being exposed to bright light. Control pregnant females were left undisturbed in their home cages. Anxiety and depressive-like behavior was measured in the offspring at an age of 6 months using the open field test, the home cage emergence test and the forced swim test. Prenatally stressed rats spent more time in the corners and less time along the walls of an open field, while no difference in total distance moved was observed. In addition, prenatally stressed rats took more time to leave their home cage in the home cage emergence test. On the other hand, no differences in immobility were observed in the forced swim test. Moreover, prenatally stressed rats showed lower stress-induced plasma corticosterone levels compared with control rats. Prenatal stress (PS) had no effect on the number of 5-bromo-2-deoxyuridine-positive cells – used as a measure for cell proliferation – in the dentate gyrus of these rats. These data further support the idea that PS may perturb normal anxiety-related development. However, the present data also suggest that an adaptive or protective effect of PS should not be ignored. Genetic factors are likely to play a role in this respect.
- Cerebellum associated with intelligence (also plays important part in motor control)
- Cerebellum is also involved with thyroid hormones
- The Hippocampus which plays roles in short/long term memory and spatial navigation are dependent on thyroid hormone for proper functioning and development
Cerebellar brain volume accounts for variance in cognitive performance in older adults
http://www.ncbi.nlm.nih.gov/pubmed/20167312
Cognitive and motor function and the size of the cerebellum in adolescents born very pre-term
http://brain.oxfordjournals.org/content/124/1/60.full.pdf
Thyroid hormones, brain function and cognition: a brief review.
http://www.ncbi.nlm.nih.gov/pubmed/11835983
In addition to their role in cellular metabolic activity, thyroid hormones (THs), also regulate neural development; the central nervous system is particularly dependent on TH for normal maturation and function. Specifically, there appears to be extensive inter-reliance between TH and acetylcholine (Ach), nerve growth factor and hippocampal function. These associations led us to investigate the possible effects of thyroxine (L-T4) on performance of a spatial learning task, where cholinergic activity and hippocampal function are known to be important. Groups of rats (n=20) received saline (controls) or L-T4 at 2.5 or 5mg/kg daily for 4 days as a sub-chronic treatment, or 0, 5 or 10mg/kg doses administered every third day for 28 days prior to testing as a chronic regimen. Rats were assessed in a water maze for their ability to find a submerged or visible platform. Forty minutes prior to water maze testing, half the animals in each group received 1mg/kg scopolamine to elicit a cognitive deficit. Following testing, rats were decapitated, blood samples taken, and the frontal cortex and hippocampus were dissected out for acetylcholinesterase (AChE) assay. The results showed that L-T4 treatment, administered both sub-chronically and chronically, significantly enhanced the ability of rats to learn a spatial memory task, compared with controls. Moreover, both short-term and long-term L-T4 treatment reduced the cognitive-impairing effects of scopolamine. Improvements in performance were shown to occur alongside significantly increased cholinergic activity in frontal cortex and in the hippocampus of treated animals. These findings demonstrate an augmentative effect of L-T4 upon cognitive function, possibly mediated by an enhancement of cholinergic activity. The results support previous findings of a relationship between L-T4 and acetylcholine, and underscore possible mechanisms by which disorders of thyroid function may be associated with cognitive decline.
Maternal stress produces learning deficits associated with impairment of NMDA receptor-mediated synaptic plasticity.
http://www.ncbi.nlm.nih.gov/pubmed/16554481
Stress in adulthood can have a profound effect on physiology and behavior, but the extent to which prolonged maternal stress affects the brain function of offspring when they are adult remains primarily unknown. In the present work, chronic immobilization stress to pregnant mice affected fetal growth and development. When pups born from stressed mice were reared to adulthood in an environment identical to that of nonstressed controls, several physiological parameters were essentially unaltered. However, spatial learning and memory was significantly impaired in the maternally stressed offspring in adulthood. Furthermore, electrophysiological examination revealed a significant reduction in NMDA receptor-mediated long-term potentiation in the CA1 area of hippocampal slices. Subsequent biochemical analysis demonstrated a substantial decrease in NR1 and NR2B subunits of the NMDA receptor in synapses of the hippocampus, and the interaction between these two subunits appeared to be reduced. These results suggest that prolonged maternal stress leads to long-lasting malfunction of the hippocampus, which extends to and is manifested in adulthood.
Thyroid hormone and central nervous system development
http://joe.endocrinology-journals.org/content/165/1/1.full.pdf
It is well established that the thyroid status of neonates and children has a significant long-term impact on their behaviour, locomotor ability, speech, hearing and cognition (Legrand 1986). Delay in restoring normal thyroid status in the neonate can lead to irreversible damage. Prompt thyroid supplementation following the diagnosis of neonatal hypothyroidism can restore neurodevelopment to within the normal range (Fisher 1979). Even so, there are still subtle abnormalities of language, visuo-spatial impairments and lower mean IQs later in childhood compared with euthyroid controls. This implies that brain development may, in part, be thyroid hormone sensitive not only in the neonatal period but also prior to birth (New England Congenital Collaborative 1990, Heyerdahl 1991). Development of different areas of central nervous sytem has been associated with the timing and duration of thyroid hormone deficiency, suggesting that there are critical periods during which various parts of the brain are sensitive to thyroid hormone supply (Rovet et al. 1992).
Transient stimulation of myelin basic protein gene expression in differentiating cultured oligodendrocytes: a model for 3,5,3'-triiodothyronine-induced brain development.
http://www.ncbi.nlm.nih.gov/pubmed/9002997
We compared the regulation of myelin basic protein (MBP) gene expression by T3 in differentiating oligodendrocytes in culture with that previously observed by us in the neonatal rat brain. As in intact brain, expression of the T3R alpha gene preceded that of the T3R beta gene. Although the absence of T3 retarded the rate of accumulation of MBP messenger RNA, the level ultimately attained was similar to that reached in the presence of T3. This relationship mirrored the pattern observed in the neonatal brain. Transient transfection experiments showed that T3 regulates MBP expression at the transcriptional level, but only for a limited period during differentiation. These observations imply that the early rise of MBP messenger RNA is T3 dependent, whereas the terminal levels are maintained independently of T3. Both the T3-dependent and, surprisingly, the T3-independent expression of MBP require the presence of an intact T3 response element. T3 receptor may regulate MBP expression in a ligand-independent manner, or a nuclear factor other than T3 receptor may bind to the T3 response element of MBP to regulate terminal gene expression. These findings support the use of differentiating oligodendrocytes as a model of T3-induced brain development.
Prevalence of thyroid disorders in untreated adult celiac disease patients and effect of gluten withdrawal: an Italian multicenter study.
http://www.ncbi.nlm.nih.gov/pubmed/11280546
Thyroid disease was 3-fold higher in patients than in controls (p < 0.0005). Hypothyroidism, diagnosed in 31 patients (12.9%) and nine controls (4.2%), was subclinical in 29 patients and of nonautoimmune origin in 21. There was no difference regarding hyperthyroidism, whereas autoimmune thyroid disease with euthyroidism was present in 39 patients (16.2%) and eight controls (3.8%). In most patients who strictly followed a 1-yr gluten withdrawal (as confirmed by intestinal mucosa recovery), there was a normalization of subclinical hypothyroidism. Twenty-five percent of patients with euthyroid autoimmune disease shifted toward either a subclinical hyperthyroidism or subclinical hypothyroidism; in these subjects, dietary compliance was poor. In addition, 5.5% of patients whose thyroid function was normal while untreated developed some degree of thyroid dysfunction 1 yr later.
Maternal thyroid hormones early in pregnancy and fetal brain development
http://www.bprcem.com/article/S1521-690X(04)00022-3/abstract
During the last few decades our understanding of the possible role of thyroid hormones during brain development has increased and contributed to resolve previously discordant hypotheses, although much remains to be clarified. Thyroid hormones of maternal origin are present in the fetal compartment, despite the very efficient uterine-placental ‘barrier’, necessary to avoid potentially toxic concentrations of free T4 and T3 from reaching fetal tissues before they are required for development. T3 remains low throughout pregnancy, whereas FT4 in fetal fluids increases rapidly to adult levels, and is determined by the maternal availability of T4. It is present in embryonic fluids 4 weeks after conception, with FT4 steadily increasing to biologically relevant values. T3, generated from T4 in the cerebral cortex, reaches adult values by mid-gestation and is partly bound to specific nuclear receptor isoforms. Iodothyronine deioidinases are important for the spatial and temporal regulation of T3 bioavailability, tailored to the differing and changing requirements of thyroid hormone-sensitive genes in different brain structures, but other regulatory mechanism(s) are likely to be involved. Maternal transfer constitutes a major fraction of fetal serum T4, even after onset of fetal thyroid secretion, and continues to have an important protective role in fetal neurodevelopment until birth.
Prompt treatment of maternal hypothyroidism, identified by increased TSH, is being advocated to mitigate a negative effect on the woman and her child. However, even a moderate transient period of maternal hypothyroxinemia at the beginning of rat neurogenesis disrupts neuronal migration into cortical layers. These findings reinforce the epidemiological evidence that early maternal hypothyroxinemia—when neuronal migratory waves are starting—is potentially damaging for the child. Detection of an inappropiate first trimester FT4 surge that may not result in increased TSH, may be crucial for the prevention of learning disabilities in a significant number of unborn children.
Role of thyroid hormone during early brain development
http://www.eje.org/content/151/Suppl_3/U25.short
Socio-spatial criteria are important for the establishment of maternal preference in lambs
http://www.journals.elsevierhealth.com/periodicals/applan/article/S0168-1591(05)00220-0/abstract
At lambing, ewes (Ovis aries) tend to isolate themselves from the flock and this is believed to be beneficial to the early relationship with their young. Later, they return to the flock and lambs progressively interact with other conspecifics. This study focused on the importance of isolation and socio-spatial factors on maternal recognition in lambs. All the ewes gave birth in individual 2m2 pens and lambs were able to interact freely with their mothers. A first experiment investigated the role of isolation: INT1 lambs could progressively interact with other mothers and young in a pen which was increased in surface area from birth to 24h (0–6h: 1 ewe, 1 litter, 2m2; 6–12h: 2 ewes, 2 litters, 4m2; 12–24h: 4 ewes, 4 litters, 8m2); ISO lambs remained in small pens (2m2) and only with their mothers for 24h. The lambs were submitted to a 5min choice test between their own mothers and an alien ewe. At 12h INT1 lambs, unlike ISO lambs, showed a clear preference for their mothers. ISO lambs still did not show any maternal preference at 24h. The second experiment investigated the relative importance of social interactions while keeping the same space allowance for the two groups: INT2 lambs as described for INT1 in Experiment 1, and SPA lambs that remained isolated from the flock with their mothers but had the same increase in pen surface area as INT2 lambs. Both INT2 and SPA lambs displayed a preference for their own mothers at 12h but INT2 lambs did so more rapidly. Our data also suggest that INT1 and INT2 lambs chose their own mothers at a distance. These results demonstrate that progressively increasing social interactions with flock members other than the mother facilitates the establishment of a preference for the mother in lambs. Increasing space allowance only also seems to have facilitating effects. This suggests that a rich socio-spatial environment from birth has beneficial effects on the development of filial bonding.
Prenatal stress and cognitive development and temperament in infants
http://www.neurobiologyofaging.org/article/S0197-4580(03)00050-2/abstract
Studies in rodents and nonhuman primates indicate that maternal stress during pregnancy can influence the developing fetus, resulting in delay of motor and cognitive development and impaired adaptation to stressful situations. These effects may be mediated by the hypothalamic–pituitary–adrenal (HPA) axis. We examined whether stress during pregnancy predicted developmental outcome of human infants in a prospective design. Self-report data about daily hassles and pregnancy-specific anxiety and salivary cortisol levels were collected in nulliparous pregnant women. Dependent measures were scores on the Bayley Scales of Infant Development and on temperamental questionnaires at 3 and 8 months. Pregnancy-specific anxiety in mid pregnancy predicted lower mental and motor developmental scores at 8 months. Early morning values of cortisol in late pregnancy were negatively related to both mental and motor development at 3 months and motor development at 8 months. Pregnancy-specific anxiety explained 7% of the variance of test-affectivity and goal-directedness at 8 months. Increased maternal stress during pregnancy seems to be one of the determinants of temperamental variation and delay of development of infants and may be a risk factor for developing psychopathology later in life.
Prenatal Restraint Stress and Long-Term Affective Consequences
http://www.karger.com/Article/FullText/86711
Chronic or repeated stress during critical periods of human fetal brain development has been associated with various learning, behavioral and/or mood disorders in later life. In this investigation, pregnant Fischer 344 rats was individually restrained three times a day for 45 min during the last week of gestation in transparent plastic cylinders while at the same time being exposed to bright light. Control pregnant females were left undisturbed in their home cages. Anxiety and depressive-like behavior was measured in the offspring at an age of 6 months using the open field test, the home cage emergence test and the forced swim test. Prenatally stressed rats spent more time in the corners and less time along the walls of an open field, while no difference in total distance moved was observed. In addition, prenatally stressed rats took more time to leave their home cage in the home cage emergence test. On the other hand, no differences in immobility were observed in the forced swim test. Moreover, prenatally stressed rats showed lower stress-induced plasma corticosterone levels compared with control rats. Prenatal stress (PS) had no effect on the number of 5-bromo-2-deoxyuridine-positive cells – used as a measure for cell proliferation – in the dentate gyrus of these rats. These data further support the idea that PS may perturb normal anxiety-related development. However, the present data also suggest that an adaptive or protective effect of PS should not be ignored. Genetic factors are likely to play a role in this respect.
