Nuanchan Jutapakdeegul

Exercise during pregnancy increases hippocampal brain-derived neurotrophic factor mRNA expression and spatial learning in neonatal rat pup

Physical activities for a few days can increase brain-derived neurotrophic factor (BDNF) mRNA in rat hippocampus. To investigate the influence of maternal exercise during pregnancy on rat pup hippocampal BDNF mRNA, we studied its expression by a semi-quantitative RT-PCR method after young pregnant rats were exercised on a motor driven treadmill. Pups of exercised mothers had significantly increased hippocampal BDNF mRNA expression compared to the control rat pups at birth (on postnatal day 0) (P<0.001). In contrast, hippocampal BDNF mRNA expression in pups of exercised mothers decreased significantly on postnatal day 28 (P<0.002). Spatial learning of rat pups was examined by multiple T maze training for 7 consecutive days between postnatal days 40 and 47. Pups of exercised mothers showed a significant increase in spatial learning ability as demonstrated by significant decreases in total time from starting to target and total number of errors as compared to age-matched control pups during the first 4 days of 7 consecutive days on multiple T maze training (P<0.05). Thus, physical exercise during gestation in pregnant mothers can increase hippocampal BDNF mRNA expression of postnatal pups and result in an improvement in spatial learning in pups from exercised dams.

Postnatal Touch Stimulation Acutely Alters Corticosterone Levels and Glucocorticoid Receptor Gene Expression in the Neonatal Rat

Environmental manipulation early in life can alter the development of the hypothalamic-pituitary-adrenal (HPA) axis by mechanisms that are still unclear. The aim of the present work was to study the acute effects of postnatal touch stimulation, in an attempt to understand the mechanism by which touch stimulation early in life alters the HPA response to stress in adult animals. Rat pups were gently brushed for 15 min daily during the 1st postnatal week. Serum corticosterone levels were determined by radioimmunoassays, while glucocorticoid receptor (GR) gene expression was assayed by semiquantitative reverse transcriptase-polymerase chain reaction. Touch stimulation induced a significant decrease (30–36%) in serum corticosteroid secretion during the 1st and 2nd postnatal day as compared to the unstimulated group. In contrast, GR gene expression in the touch stimulation group was significantly increased in several brain areas such as the hippocampus (19–21%), frontal cortex (26–34%) and midbrain (15–24%). The results thus indicate that neonatal touch stimulation causes acute hormone- secretion and gene-expression changes within the period of stimulation. These changes may be the underlying cause for the permanent changes that have been observed in adult animals touch-stimulated as neonates.

Repeated restraint stress and corticosterone injections during late pregnancy alter GAP-43 expression in the hippocampus and prefrontal cortex of rat pups

In the offspring of prenatal stress animals, overactivity and impaired negative feedback regulation of the hypothalamic–pituitary–adrenal axis are consistent finding. However, little was known about how prenatal stress can permanently alter developmental trajectories of pups brain. Growth‐associated protein‐43 (GAP‐43) is a presynaptic membrane phosphoprotein whose expression increases during developmental events such as axonal outgrowth or remodeling and synaptogenesis. Phosphorylation of GAP‐43 by protein kinase C was correlated with enhanced axonal growth and transmitter release. In adult animals, increase of GAP‐43 correlated with monoaminergic deficit in neuropsychiatric disorders. The present study examines the effects of repeated maternal restraint stress on the level of GAP‐43 in the brain of rat pups. The results showed that prenatal stress significantly increased GAP‐43 level in the PFC of rat pup during PND 7–14 as compared to control but not significant difference when observed at PND 21. Increased GAP‐43 expression was also observed in the pups hippocampus during the same postnatal periods. However, when observed at PND 60, pups born from stressed mother showed a significant lower (p < 0.001) GAP‐43 expression as compare with control group. These changes indicate the direct effect of corticosteroid hormone, since repeated maternal injection with corticosterone (CORT, 40 mg/kg) during GD 14–21 also gave the same results. PND 7–14 is the peak period of synaptogenesis in these brain areas and abnormal axon sprouting and reorganization may lead to a defect in synaptic pruning at later stage of life. The results suggested that maternal stress is harmful to the developing brain and upregulation of GAP‐43 indicated a protective mechanism against the toxicity of maternal stress hormone. Prenatal stress alter the normal developmental trajectories in the pups brain may underlies the mechanism link between early life stress and neuropsychopathology in later life.

The opioid receptors in inner ear of different stages of postnatal rats

There is increasing evidence that the opioid system has a role in hearing. To provide further evidence for such a role, the expression of opioid receptor mRNAs and proteins in the inner ear of rats was studied during development from birth (P0) to postnatal day 16 (P16). A semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was employed to detect changes in the expression of delta- (DOR) kappa- (KOR) and mu- (MOR) opioid receptor mRNAs in rat cochleae at P0, P4, P8 and P16. Expression of DOR mRNA levels steadily increased from P0 to P8 with no further increases by P16. KOR mRNA was expressed at a relatively high level at P0 and P4 followed by a decrease while MOR mRNA was expressed at a low level at P0 and P4 followed by an increase by P8 and P16. Immunocytochemical labelling of inner ear sections revealed unique developmental and distribution patterns of opioid receptors. In the organ of Corti DOR immunoreactivity (DOR-IR) was detected in hair cells from P4. In contrast MOR-IR was present only in supporting cells at P0-P16. In the spiral ganglion all three receptor subtypes were expressed from P0 on nerve cell soma and qualitatively appeared to increase with age. Also DOR-IR and MOR-IR were detected at P8 and P16 in nerve fibers within the spiral ganglion. In the limbus DOR-IR was detected at P8 and P16 on cells proximal to the tectorial membrane while MOR-IR was detected more distally. In general these findings demonstrate that within the inner ear each receptor subtype follows specific temporal and spatial developmental patterns, some of which may be associated to the onset of hearing. The data provide further evidence that the opioid system may play a role in the development and functioning of the inner ear.

Influence of music training on academic examination-induced stress in Thai adolescents

Several pieces of evidence suggest that academic examinations fulfill the classical requirement of a psychological stressor. Academic examinations represent a stressful challenge to many students, but studies on examination-dependent corticosteroid response, a sensitive physiological indicator of a stress response, are inconsistent. In addition, several studies showed that music can decrease cortisol and adrenocorticotropic hormone (ACTH) levels, and other studies have found that music also may enhance a variety of cognitive functions, such as attention, learning, communication and memory. The present study investigated cortisol response in saliva of Thai adolescents taking academic examinations and analyzed the differences of the stress response between musician and control subjects. Also, we observed whether the academic examination-dependent corticosteroid response affected learning and memory in the test subjects, which comprised 30 musician and 30 control students, age ranging from 15 to 17 years. Mathematical examinations were used as the stressor. Pre- and post-academic examination saliva cortisol levels were measured including self-estimated stress levels. Results showed that the pre-academic examination saliva cortisol concentrations of the musician group are significantly lower than those of the control group, whereas there is no difference in the stress inventory scores. Interestingly, among students with grade point average (GPA) of >3.50, pre-academic examination cortisol levels are significantly lower in the musician compared with control group. This study suggests that under academic examination-induced stress condition, music training can reduce saliva cortisol level in Thai adolescents.

Repeated carbenoxolone injection during late pregnancy decreased SPAR but increased Snk expression in the hippocampus of rat pups

Homeostasis of circulating cortisol is maintained by two enzymes of 11 -hydroxysteroid dehydrogenase, 11 -HSD1 and 11 -HSD2. 11 -HSD2 is NAD-dependent dehydrogenase that inactivates cortisol into cortisone. In addition, 11 -HSD2 is abundantly expressed in the placenta where it protects the fetus from active maternal glucocorticoids. Administration of carbenoxolone (CBX), a powerful 11 -HSD2 inhibitor, leads to an increased of fetal cortisol level and decreased plasma cortisone levels. Previous data showed that intrauterine environment plays crucial roles in determining hippocampal structure and function in later life. Exposure to high level of corticosteroid during pregnancy lead to a low birth weight offspring, increased risk of aged related memory and cognitive deficits, however, mechanism still unclear. We proposed that repeated CBX injections during late pregnancy may alter scaffolding proteins of NMDA receptor in the hippocampus of rat pups. Here we show that pregnant rats receiving CBX injections (30 mg/kg) during GD14-21 lead to a significant decreased of SPAR (spine Associated Rap Guanylate kinase activating protein) (p < 0.01) but significant increased of Snk (Serum inducible kinase) (p < 0.01) in the pup’s hippocampus at P40 and P60, while the level of PSD-95 remain unchanged. NMDA receptor function has been shown to be influenced by turnover of the scaffolding proteins via ubiquitin proteasome system (UPS). Normally, Snk is induced by neuronal activity and plays an important role in phosphorylate SPAR. The phosphorylated SPAR was then recognized and degraded by ubiquitin-proteasome system, causing the depletion of SPAR and PSD-95 from the spines and leading to spine shrinkage and loss. The results suggest that fetal exposure with excessive corticosteroids may activate Snk/SPAR pathway and lead to the depletion of SPAR. Since, corticosteroid drugs are commonly used in various obstetric and paediatric conditions, it is important to consider the risk–benefit of prenatal GC exposure to prevent the neurodevelopment delay in the offspring.

Repeated maternal restraint stress down-regulated NMDA receptor subunits and scaffolding proteins in the hippocampus of postnatal rat

Homeostasis of circulating cortisol is maintained by two enzymes of 11 -hydroxysteroid dehydrogenase, 11 -HSD1 and 11 -HSD2. 11 -HSD2 is NAD-dependent dehydrogenase that inactivates cortisol into cortisone. In addition, 11 -HSD2 is abundantly expressed in the placenta where it protects the fetus from active maternal glucocorticoids. Administration of carbenoxolone (CBX), a powerful 11 -HSD2 inhibitor, leads to an increased of fetal cortisol level and decreased plasma cortisone levels. Previous data showed that intrauterine environment plays crucial roles in determining hippocampal structure and function in later life. Exposure to high level of corticosteroid during pregnancy lead to a low birth weight offspring, increased risk of aged related memory and cognitive deficits, however, mechanism still unclear. We proposed that repeated CBX injections during late pregnancy may alter scaffolding proteins of NMDA receptor in the hippocampus of rat pups. Here we show that pregnant rats receiving CBX injections (30 mg/kg) during GD14-21 lead to a significant decreased of SPAR (spine Associated Rap Guanylate kinase activating protein) (p < 0.01) but significant increased of Snk (Serum inducible kinase) (p < 0.01) in the pup’s hippocampus at P40 and P60, while the level of PSD-95 remain unchanged. NMDA receptor function has been shown to be influenced by turnover of the scaffolding proteins via ubiquitin proteasome system (UPS). Normally, Snk is induced by neuronal activity and plays an important role in phosphorylate SPAR. The phosphorylated SPAR was then recognized and degraded by ubiquitin-proteasome system, causing the depletion of SPAR and PSD-95 from the spines and leading to spine shrinkage and loss. The results suggest that fetal exposure with excessive corticosteroids may activate Snk/SPAR pathway and lead to the depletion of SPAR. Since, corticosteroid drugs are commonly used in various obstetric and paediatric conditions, it is important to consider the risk–benefit of prenatal GC exposure to prevent the neurodevelopment delay in the offspring.