Effects of Neonatal Tactile Stimulation and Maternal Separation on the Anxiety and the Emotional Memory in Adult Female Rats

We investigated the long-lasting effects of early postnatal tactile stimulation （TS） and maternal separation （MS） on the emotional behaviors of adult female rats. A split-litter design was introduced to remove confusing factors such as maternal disturbance. Pups of the non-tactile stimulation （NTS） group did not receive any handling. Pups subjected to the TS treatment were handled and marked for approximately 30 s daily from postnatal days （PND） 2 - 9 or from PND 10 - 17. Pups subjected to the MS treatment were handled and marked in the same way as the TS pups and then individually placed in a cup with familiar nest bedding for 1 h daily. At the age of 3 months, female rats with different neonatal experiences were employed in the light/dark box test and the one-trial passive avoidance response. Both PND 2 - 9 TS and PND 10 - 17 TS groups exhibited more time spent in the illuminated chamber of the light/dark box, and longer step-through latencies in the passive avoidance response when compared to the NTS group, indicating that early life TS treatment reduced novelty-induced anxious emotion and facilitated the retention of emotional memory in adult female rats. No significant effects were found on any behavioral measures between the MS groups and the TS groups, suggesting that neonatal short-time MS treatment was not intensive enough to alter the emotional behaviors, at least in female rats. Infantile age was not an effective factor for these measures. This result supports the hypothesis that neonatal tactile stimulation and maternal separation lead to different effects on the neural development of postnatal pups.

Analgesic effects of JCM-16021 on neonatal maternal separation-induced visceral pain in rats

AIM:To investigate the pharmacological effect of JCM-16021,a Chinese herbal formula,and its underlying mechanisms.METHODS:JCM-16021 is composed of seven herbal plant materials.All raw materials of the formula were examined according to the quality control criteria listed in the Chinese Pharmacopeia(2005).In a neonatal maternal separation(NMS)model,male SpragueDawley rats were submitted to daily maternal separation from postnatal day 2 to day 14,or no specific handling(NH).Starting from postnatal day 60,rats were administered JCM-16021(2,4,8 g/kg per day)orally twice a day for 28 d.Pain threshold pressure and electromyographic activities of external oblique muscles in response to colorectal distention recorded with a Power Lab System(AD Instruments International),were tested as pain indices.Changes in serotonin(5-HT)and 5-hydroxyindoleacetic acid(5-HIAA)concentrations in the colon of rats were analyzed;the enterochromaffin cell numbers and serotonin transporter in the colon of rats were also evaluated with an immunohistochemistry method.RESULTS:NMS treatment significantly reduced pain threshold pressure(37.4±1.4 mmHg),as compared to that of NH rats(57.7±1.9 mmHg,P<0.05).After JCM-16021 treatment,the pain threshold pressure significantly increased when compared to that before treatment(34.2±0.9 mmHg vs 52.8±2.3 mmHg in the high dose group,40.2±1.6 mmHg vs 46.5±1.3 mmHg in the middle dose group,and 39.3±0.7 mmHg vs 46.5±1.6 mmHg in the low dose group,P<0.05).Also JCM-16021 significantly and dose-dependently decreased electromyographic activity to the graded colorectal distension(CRD),(the meanΔAUC values were:0.17±0.03,0.53±0.15,1.06±0.18,1.22±0.24 in the high dose group;0.23±0.04,0.68±0.17,1.27 ±0.26,1.8±0.3 in the middle dose group;and 0.29 ±0.06,0.8±0.16,1.53±0.24,2.1±0.21 in the low dose group for the pressures 20,40,60,80 mmHg),as compared to the NMS vehicle group.The meanΔAUC values were:0.57±0.12,1.33±0.18,2.57±0.37,3.08±0.37 for the pressures 20,40,60,80 mmHg(P <0.05).JCM-16021 treatment significantly reduced the 5-HT concentrations(from high,middle and low dosage groups:60.25±5.98 ng/100 mg,60.32±4.22 ng/100 mg,73.31±7.65 ng/100 mg),as compared to the NMS vehicle groups(93.11±9.85 ng/100 mg,P<0.05);and increased the 5-HIAA concentrations(after treatment,from high,middle and low dosage groups:54.24±3.27 ng/100 mg,50.34±1.26 ng/100 mg,51.37±2.13 ng/100 mg)when compared to that in the NMS vehicle group(51.75±1.98 ng/100 mg,P <0.05);but did not change the enterochromaffin cell numbers in the colon of rats.In addition,NMS rats had higher SERT expression(n=10)than NH rats(n=8,P<0.05).JCM-16021 treatment significantly decreased SERT expression when compared to the NMS group(P <0.01-0.001).CONCLUSION:JCM-16021 can attenuate visceral hypersensitivity,and this analgesic effect may be mediated through the serotonin signaling pathway in the colon of rats.

Adverse effects of early-life stress:focus on the rodent neuroendocrine system

Early-life stress is associated with a high prevalence of mental illnesses such as post-traumatic stress disorders,attention-deficit/hyperactivity disorder,schizophrenia,and anxiety or depressive behavior,which constitute major public health problems.In the early stages of brain development after birth,events such as synaptogenesis,neuron maturation,and glial differentiation occur in a highly orchestrated manner,and external stress can cause adverse long-term effects throughout life.Our body utilizes multifaceted mechanisms,including neuroendocrine and neurotransmitter signaling pathways,to appropriately process external stress.Newborn individuals first exposed to early-life stress deploy neurogenesis as a stress-defense mechanism;however,in adulthood,early-life stress induces apoptosis of mature neurons,activation of immune responses,and reduction of neurotrophic factors,leading to anxiety,depression,and cognitive and memory dysfunction.This process involves the hypothalamus-pituitary-adrenal axis and neurotransmitters secreted by the central nervous system,including norepinephrine,dopamine,and serotonin.The rodent early-life stress model is generally used to experimentally assess the effects of stress during neurodevelopment.This paper reviews the use of the early-life stress model and stress response mechanisms of the body and discusses the experimental results regarding how early-life stress mediates stress-related pathways at a high vulnerability of psychiatric disorder in adulthood.

Distinct neuronal excitability alterations of medial prefrontal cortex in early-life neglect model of rats

Object:Early-life neglect has irreversible emotional effects on the central nervous system.In this work,we aimed to elucidate distinct functional neural changes in me-dial prefrontal cortex(mPFC)of model rats.Methods:Maternal separation with early weaning was used as a rat model of early-life neglect.The excitation of glutamatergic and GABAergic neurons in rat mPFC was recorded and analyzed by whole-cell patch clamp.Results:Glutamatergic and GABAergic neurons of mPFC were distinguished by typi-cal electrophysiological properties.The excitation of mPFC glutamatergic neurons was significantly increased in male groups,while the excitation of mPFC GABAergic neurons was significant in both female and male groups,but mainly in terms of rest membrane potential and amplitude,respectively.Conclusions:Glutamatergic and GABAergic neurons in medial prefrontal cortex showed different excitability changes in a rat model of early-life neglect,which can contribute to distinct mechanisms for emotional and cognitive manifestations.

Study on the Lactation Volume and Related Factors of Mother’s Milk in Puerperal Women Separated from Infant

Objective: To investigate the lactation volume and milk secretion of mother’s milk in puerperal women separated from mother and infant, and to study the related influencing factors. Methods: Selected February 2015-February 2020 in Foshan women and children’s hospital 420 cases of maternal as the research object, using lactation related factors comprehensive questionnaire of maternal and infant separation of puerperal women for continuous determination of amount of lactation, and 1 - 7 days and 8 to 14 days postpartum lactation quantity and Pearson correlation analysis, using multiple linear regression analysis to affect maternal separation of puerperal women in lactation of breast volume related factors were analyzed. Results: The lactation volume of the puerperal women was on the rise within 14 days after delivery. 14 days mammary volume ware 545.13 - 243.18 ml, postpartum lactation II period start time was (67.48 + 26.57) h. The correlation coefficient between lactation volume on day 4 and lactation volume on day 14 was 0.04 (P < 0.05). Pregnancy-induced hypertension syndrome, lactation II period start time, birth gestational age, maternal age is affecting maternal separation of the main factors of puerperal women lactation milk. Conclusion: Early maternal separation of puerperal women breast milk lactation quantity is little, lactation II later period start time, delay rate is high: in clinical nursing work, should pay attention to produce age is bigger, smaller gestational age and birth with pregnancy-induced hypertension syndrome, maternal lactation stage II startup delay, should be timely intervention of maternal and infant separation maternal management effectively, promote successful lactation and increase the amount of lactation, for clinical guidance and provides some references for the separation of puerperal women breastfeeding.

Acupuncture Alters Pro-inflammatory Cytokines in the Plasma of Maternally Separated Rat Pups

Objective: To investigate the potential alleviating effects of acupuncture on maternal separation(MS)-induced changes in plasma pro-inflammatory cytokine levels of rat pups. Methods: On postnatal day 15, rat pups were randomly assigned to 4 groups(n=6 per group) using a random number table: normal, MS, MS with acupuncture stimulation at Shenmen(HT 7) acupoint(MS+HT 7), and MS with acupuncture stimulation at Chengshan(BL 57) acupoint(MS+BL 57) groups. Rat pups in the normal group were housed with their mothers under standard conditions; those in the MS, MS+HT 7 and MS+BL 57 groups were maternally separated and individually maintained. Acupuncture stimulation was performed at HT 7 or BL 57 acupoints once a day for 7 consecutive days. A tail suspension test was performed to measure immobility time of rats and the plasma was collected on postnatal day 21, then levels of corticosterone(CORT), interleukin(IL)-1β, IL-6 and glial cell-derived neurotrophic factor(GDNF) in plasma were measured. Results: Compared with the normal group, the immobility time and the plasma levels of CORT, IL-1β, IL-6 and GDNF in the MS group were significantly increased(P<0.05 or P<0.01). Compared with the MS group, the immobility time and the plasma levels of CORT, IL-1β, IL-6 and GDNF were significantly reduced in the MS+HT 7 group(P<0.05 or P<0.01). Moreover, the immobility time and plasma levels of IL-1β and IL-6 in the MS+HT 7 group were significantly lower than those in the MS+BL 57 group(P<0.05). Conclusion: Acupuncture stimulation at HT 7 can alleviate the behavioral impairment and changes of the cytokines by MS, indicating that acupuncture can help to relieve MS-induced depression.