Human Brain Slice Culture: A Useful Tool to Study Brain Disorders and Potential Therapeutic Compounds / 神经科学通报·英文版

Investigating the pathophysiological mechanisms underlying brain disorders is a priority if novel therapeutic strategies are to be developed. In vivo studies of animal models and in vitro studies of cell lines/primary cell cultures may provide useful tools to study certain aspects of brain disorders. However, discrepancies among these studies or unsuccessful translation from animal/cell studies to human/clinical studies often occur, because these models generally represent only some symptoms of a neuropsychiatric disorder rather than the complete disorder. Human brain slice cultures from postmortem tissue or resected tissue from operations have shown that, in vitro, neurons and glia can stay alive for long periods of time, while their morphological and physiological characteristics, and their ability to respond to experimental manipulations are maintained. Human brain slices can thus provide a close representation of neuronal networks in vivo, be a valuable tool for investigation of the basis of neuropsychiatric disorders, and provide a platform for the evaluation of novel pharmacological treatments of human brain diseases. A brain bank needs to provide the necessary infrastructure to bring together donors, hospitals, and researchers who want to investigate human brain slices in cultures of clinically and neuropathologically well-documented material.

Quantification of Tyrosine Hydroxylase and ErbB4 in the Locus Coeruleus of Mood Disorder Patients Using a Multispectral Method to Prevent Interference with Immunocytochemical Signals by Neuromelanin / 神经科学通报·英文版

The locus coeruleus (LC) has been studied in major depressive disorder (MDD) and bipolar disorder (BD). A major problem of immunocytochemical studies in the human LC is interference with the staining of the immunocytochemical end-product by the omnipresent natural brown pigment neuromelanin. Here, we used a multispectral method to untangle the two colors: blue immunocytochemical staining and brown neuromelanin. We found significantly increased tyrosine hydroxylase (TH) in the LC of MDD patients-thus validating the method-but not in BD patients, and we did not find significant changes in the receptor tyrosine-protein kinase ErbB4 in the LC in MDD or BD patients. We observed clear co-localization of ErbB4, TH, and neuromelanin in the LC neurons. The different stress-related molecular changes in the LC may contribute to the different clinical symptoms in MDD and BD.

Activation of the Brain to Postpone Dementia: A Concept Originating from Postmortem Human Brain Studies / 神经科学通报·英文版

Alzheimer's disease (AD) is characterized by decreased neuronal activity and atrophy, while hyperactivity of neurons seems to make them resistant to aging and neurodegeneration, a phenomenon which we have paraphrased as 'use it or lose it'. Our hypothesis proposes that (1) during their functioning, neurons are damaged; (2) accumulation of damage that is not repaired is the basis of aging; (3) the vulnerability to AD is determined by the genetic background and the balance between the amount of damage and the efficiency of repair, and (4) by stimulating the brain, repair mechanisms are stimulated and cognitive reserve is increased, resulting in a decreased rate of aging and risk for AD. Environmental stimulating factors such as bilingualism/multilingualism, education, occupation, musical experience, physical exercise, and leisure activities have been reported to reduce the risk of dementia and decrease the rate of cognitive decline, although methodological problems are present.

Progress in determination of histamine levels in biological samples / 浙江大学学报·医学版

Neuronal histamine is crucially involved in a number of physiological functions as well as in neuropsychiatric diseases. Determination of histamine in biological samples is thus of importance in the clinical studies. The aim of this review is to summarize the progress or effort made in this field, with focus on the high-performance liquid chromatography.

Research progress on role of ghrelin in brain / 浙江大学学报·医学版

The brain-gut peptide ghrelin, a endogenous ligand for the growth hormone secretagogue hormone receptor, is mainly produced by gastric cells in the periphery, regulating energy metabolism via stimulating the appetite. Inside the brain, ghrelin is mainly expressed in the pituitary and in the hypothalamic arcuate nucleus, regulating the synthesis and secretion of neuropeptides that are correlated with feeding behavior, reproduction, and stress responses. Recently, more and more researches focused on the regulating roles of ghrelin on learning and memory, and mood regulation have indicated that ghrelin may inhibit neuronal apoptosis, improve cognitive function, and regulate the activities of neuroendocrine systems such as the hypothalamo-pituitary-adrenal axis and the hypothalamo-pituitary-gonadal axis thus get involved in the pathogenesis of neuropsychiatric diseases. The aim of this review is to summarize the main findings in this field, with the purpose of promoting further studies on the role of ghrelin in the brain.

Maternal deprivation-induced stress responses in female rats / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effect of maternal deprivation on the activity of hypothalamo-pituitary-adrenal (HPA) axis, acute stress response and the sex hormone receptors expression in hypothalamic paraventricular nucleus (PVN) in female rats.</p><p><b>METHODS</b>Maternal deprivation model was induced in female Sprague-Dawley (SD) rats. Foot shock was given at different stages of estrus cycle during the adulthood. Plasma estradiol, testosterone and adrenocorticotropin (ACTH) levels were determined by radioimmunoassay; and plasma corticosterone level was measured by enzyme linked immunosorbent assay. The expression of androgen receptor (AR) and estrogen receptor (ER-β) in the hypothalamic PVN was detected by immunohistochemistry.</p><p><b>RESULTS</b>Decreased plasma ACTH and corticosterone levels were found in the proestrus of female rats with maternal deprivation (P=0.012 and P=0.019, respectively). A significant down-regulation (P=0.008) of PVN-AR, but not PVN-ER-β expression was found in female rats with maternal deprivation.</p><p><b>CONCLUSION</b>Maternal deprivation may reduce the HPA axis activity in female SD rats, which is closely correlated with the fluctuation of the circulating sex hormones. The androgen in the hypothalamus seems to play a more important role than the estrogen in this procedure.</p>

Alterations of plasma aspartic acid, glycine and asparagine levels in patients with major depressive disorder / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To evaluate the changes of plasma levels of the excitatory amino acid neurotransmitter aspartic acid (Asp), inhibitory neurotransmitter glycine (Gly) and asparagine (Asn) in patients with major depressive disorder (MDD).</p><p><b>METHODS</b>Plasma samples were collected from 15 MDD patients (9 males and 6 females, aged 32-64 y) and 14 healthy subjects (7 males and 7 females, aged 30-65 y); and also collected from 7 MDD patients (5 males and 2 females) 2 months after antidepressant treatment. The plasma levels of amino acids were determined by high performance liquid chromatography with fluorescence detection method.</p><p><b>RESULTS</b>Plasma Asp and Gly levels were significantly lower in MDD patients than those in controls (P<0.04). There were positive correlations between plasma levels of Gly and Asp, and between Gly and Asn (P<0.005) in the control group; while in MDD patients, a significant positive correlation was found only between plasma levels of Gly and of Asp (P<0.001). MDD patients did not show significant changes in plasma Asp, Asn and Gly levels after antidepressant treatment compared to those before treatment.</p><p><b>CONCLUSION</b>The reduced plasma Asp and Gly levels may serve as a clinical biomarker for MDD.</p>

Changes in circadian sleep-wake and rest-activity rhythms during different phases of menstrual cycle / 生理学报

The results of previous studies on the menstrual-related sleep changes were inconsistent. The menstrual-related circadian sleep-wake and rest-activity rhythms changes are still uncertain. Using actigraphic monitoring of wrist activity, we investigated the sleep-wake and rest-activity patterns of 12 normally cyclic healthy women during reproductive life. Multivariate analyses were performed during the four phases of the menstrual cycle: menstrual phase (lst to 5th day of menstrual cycle), late follicular/peri-ovulation phase (11th to 15th day), early to mid luteal phase (18th to 23rd day) and late luteal phase (25th to 28th day), respectively. The variables of circadian sleep-wake pattern were similar in the four phases, except an increased tendency of the sleep latency in peri-ovulation phase compared with the early to mid-luteal phase (19+/-18 vs 9+/-6), but unfortunately no statistical significance were found (P<0.10). Concerning the circadian patterning of rest and activity, the interdaily stability (IS) in menstrual phase was significantly higher than the early to mid luteal phase (P<0.05). In early to mid luteal phase, the M10 onset time was significantly earlier compared with that of the late follicular/peri-ovulation phase (P<0.05), and the cosinor peak time was significantly earlier compared with that of the late luteal phase (P<0.05). The circadian periodogram calculated the period length of the rhythm of average woman. The average length was (24.01+/-0.29) h, and there was no significant difference among the four menstrual phases. The results suggest that the phase of circadian rest-activity rhythm may be modulated by the menstrual cycle, but the quantity and quality of the rest-activity rhythm have no essential different, and that menstrual cycle may have no effects on the circadian sleep-wake rhythm in normally cyclic healthy women.

Changes in diurnal rhythms of free cortisol secretion during different phases of menstrual cycle / 生理学报

The effect of the menstrual cycle on the diurnal cortisol rhythm was investigated in 15 normally cyclic healthy women during reproductive life. Salivary cortisol was measured by radioimmunoassay in samples collected every 2 h for 24 h during the four phases of the menstrual cycle: menstrual phase, late follicular/peri-ovulation phase, early to mid luteal phase and late luteal phase, respectively. Distinct diurnal rhythms of free cortisol were found throughout the menstrual cycle by using a nonlinear periodic regression model. The model was characterized by an asymmetrically peaked diurnal cycle and ultradian harmonics. There was a trend to higher troughs and significantly shorter peak-width in phase II and phase IV compared to phase I. The ultradian amplitude in phase IV was significantly lower compared with phase I and showed a trend of decrease compared with phase II. The results suggest that the daily cortisol secretion is modulated by the phase of the menstrual cycle.