Neuroscience
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Melatonin, an indoleamine hormone secreted into circulation at night primarily by the brain's pineal gland, has been shown to have a wide variety of actions on the development and physiology of neurons in the CNS. Acting via two G-protein-coupled membrane receptors (MT1 and MT2), melatonin modulates neurogenesis, synaptic functions, neuronal cytoskeleton and gene expression. In the present studies, we sought to characterize the behavior and neuronal biology of transgenic mice lacking both of these melatonin receptors as a way to understand the hormone's receptor versus non-receptor-mediated actions in CNS-dependent activities, such as learning and memory, anxiety, general motor performance and circadian rhythmicity. ⋯ Electrophysiological measures in hippocampal slices revealed a clear enhancement of long-term potentiation in mice lacking melatonin receptors with no significant differences in paired-pulse facilitation. Quantitative analysis of brain protein expression levels of phosphoCREB and phosphoERK1/2 and key markers of synaptic activity (synapsin, glutamate receptor 1, spinophilin, and glutamic acid decarboxylase 1) revealed significant differences between the double-knockout and wild-type animals, consistent with the behavioral findings. Thus, genetic deletion of melatonin receptors produces mice with enhanced cognitive and motor performance, supporting the view that these receptors play an important role in neurobehavioral development.
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Evidence from the animal literature suggests that post-training glucocorticoids (GCs) interact with noradrenergic activation at acquisition to enhance memory consolidation for emotional stimuli. While there is evidence that GCs enhance memory for emotional material in humans, the extent to which this depends on noradrenergic activation at encoding has not been explored. In this study, 20-mg hydrocortisone was administered to healthy young women (18-35 yrs old) in a double-blind fashion 10 min prior to viewing a series of emotional and neutral images. ⋯ Participants returned 1 week later for a surprise recall test. Results suggest that, hydrocortisone administration resulted in emotional memory enhancement only in participants who displayed an increase in endogenous noradrenergic activation, measured via salivary alpha-amylase at encoding. These results support findings in the animal literature, and suggest that GC-induced memory enhancement relies on noradrenergic activation at encoding in women.
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Hydrocephalus is caused by the accumulation of cerebrospinal fluid (CSF) in the cerebral ventricular system which results in an enlargement of the cranium due to increased intraventricular pressure. The increase in pressure within the brain typically results in sloughing of ciliated ependymal cells, loss of cortical gray matter, and increased gliosis. Congenital hydrocephalus is associated with several syndromes including primary ciliary dyskinesia (PCD), a rare, genetically heterogeneous, pediatric syndrome that results from defects in motile cilia and flagella. ⋯ Alterations in astrocytosis, microglial activation, myelination, and the neuronal population were identified and are generally more severe on the C57BL/6J background. Analysis of ependymal ciliary clearance ex vivo and CSF flow in vivo demonstrate a physiological defect in nm1054 and bgh mice on both genetic backgrounds, indicating that abnormal cilia-driven flow is not the sole determinant of the severity of hydrocephalus in these models. These results suggest that genetic modifiers play an important role in susceptibility to severe PCD-associated hydrocephalus.
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The anterior hypothalamus (Ant Hyp) of the brain serves as the main regulator of numerous homeostatic functions, among them body temperature. Fine-tuning of the thermal-response set point during the critical postnatal sensory-developmental period involves neuronal network remodeling which might also be accompanied by alterations in hypothalamic cell populations. Here we demonstrate that heat stress during the critical period of thermal-control establishment interferes with generation of new cells in the chick hypothalamus. ⋯ Intracranial injection into the third ventricle of miR-138 led to an increase in the number of newborn cells in the Ant Hyp, an effect which might be partially mediated by inhibition of its direct target reelin. These data demonstrate the role of ambient temperature on the generation of new cells in the hypothalamus during the critical period of thermal-control establishment and highlight the long-term effect of severe heat stress on hypothalamic cell population. Moreover, miRNAs, miR-138 in particular, can regulate new cell generation in the hypothalamus.
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A previous study investigating potential adult hippocampal neurogenesis in microchiropteran bats failed to reveal a strong presence of this neural trait. As microchiropterans have a high field metabolic rate and a small body mass, it is possible that capture/handling stress may lead to a decrease in the detectable presence of adult hippocampal neurogenesis. Here we looked for evidence of adult hippocampal neurogenesis using immunohistochemical techniques for the endogenous marker doublecortin (DCX) in 10 species of microchiropterans euthanized and perfusion fixed at specific time points following capture. ⋯ Between 15 and 30 min post-capture, the detectable levels of DCX dropped dramatically and after 30 min post-capture, immunohistochemistry for DCX could not reveal any significant evidence of putative adult hippocampal neurogenesis. Thus, as with all other mammals studied to date apart from cetaceans, bats, including both microchiropterans and megachiropterans, appear to exhibit substantial levels of adult hippocampal neurogenesis. The present study underscores the concept that, as with laboratory experiments, studies conducted on wild-caught animals need to be cognizant of the fact that acute stress (capture/handling) may induce major changes in the appearance of specific neural traits.