摘要
The ventral part of the anteromedial thalamic nucleus (AMv) is in a position to convey information to the cortico-hippocampal-amygdalar circuit involved in the processing of fear memory. Corticotropin-releasing-factor (CRF) neurons are closely associated with the regulation of stress and fear. However, few studies have focused on the role of thalamic CRF neurons in fear memory. In the present study, using a conditioned fear paradigm in CRF transgenic mice, we found that the c-Fos protein in the AMv CRF neurons was significantly increased after cued fear expression. Chemogenetic activation of AMv CRF neurons enhanced cued fear expression, whereas inhibition had the opposite effect on the cued fear response. Moreover, chemogenetic manipulation of AMv CRF neurons did not affect fear acquisition or contextual fear expression. In addition, anterograde tracing of projections revealed that AMv CRF neurons project to wide areas of the cerebral cortex and the limbic system. These results uncover a critical role of AMv CRF neurons in the regulation of conditioned fear memory.
摘要
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.
Subject(s)
Humans , Brain , Brain Diseases , Drug Therapy , Tissue Culture Techniques摘要
The striatum and globus pallidus are principal nuclei of the basal ganglia. Nissl- and acetylcholinesterase-stained sections of the tree shrew brain showed the neuroanatomical features of the caudate nucleus (Cd), internal capsule (ic), putamen (Pu), accumbens, internal globus pallidus, and external globus pallidus. The ic separated the dorsal striatum into the Cd and Pu in the tree shrew, but not in rats and mice. In addition, computer-based 3D images allowed a better understanding of the position and orientation of these structures. These data provided a large-scale atlas of the striatum and globus pallidus in the coronal, sagittal, and horizontal planes, the first detailed distribution of parvalbumin-immunoreactive cells in the tree shrew, and the differences in morphological characteristics and density of parvalbumin-immunoreactive neurons between tree shrew and rat. Our findings support the tree shrew as a potential model for human striatal disorders.
Subject(s)
Animals , Male , Mice , Rats , Acetylcholinesterase , Metabolism , Brain Mapping , Corpus Striatum , Cell Biology , Metabolism , Globus Pallidus , Cell Biology , Metabolism , Imaging, Three-Dimensional , Mice, Inbred C57BL , Models, Neurological , Neurons , Metabolism , Parvalbumins , Metabolism , Rats, Sprague-Dawley , Statistics, Nonparametric , Tupaiidae摘要
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.
Subject(s)
Female , Humans , Activity Cycles , Physiology , Circadian Rhythm , Luteal Phase , Physiology , Menstrual Cycle , Physiology , Sleep , Physiology , Wakefulness , Physiology摘要
<p><b>OBJECTIVE</b>To investigate the possible mechanism by which estrogen regulates apoptosis through the estrogen receptor.</p><p><b>METHODS</b>By means of fluorescence immunocytochemistry, the present study investigated the distribution of Bcl-2 and the colocolization of Bcl-2 and ERalpha immunoreactivity in the hippocampus of 10 Alzheimer's disease (AD) patients and 10 aged controls.</p><p><b>RESULTS</b>Bcl-2 immunoreactivity was widely distributed in neurons, concentrating predominantly on the subfields CA3 and CA4 in the stratum pyramidale of hippocampus both in controls and in AD patients. Bcl-2 staining in the labeled neuron was observed mainly in the cytoplasm and neuritic processes, but a few nuclei were also positive. Bcl-2 labeling was also detected in the astrocytes mainly in AD, but sparsely in controls. Double-labeled fluorescence immunocytochemistry showed that most Bcl-2-immunolabeled neurons also exhibited positive staining for ERalpha.</p><p><b>CONCLUSIONS</b>Estrogen may function as a regulator of apoptosis to modulate the expression of Bcl-2 in neurons and astrocytes in hippocampus of AD through ERalpha.</p>
Subject(s)
Female , Humans , Alzheimer Disease , Genetics , Metabolism , Apoptosis , Astrocytes , Metabolism , Estrogen Receptor alpha , Hippocampus , Metabolism , Pathology , Neurons , Metabolism , Proto-Oncogene Proteins c-bcl-2 , Genetics , Receptors, Estrogen , Genetics , Metabolism , Physiology摘要
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.