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Developmental Neurobiology Aug 2011Neurogenesis in the adult brain, a process once thought to be essentially absent, has now been demonstrated to occur throughout adult mammalian life within several brain... (Review)
Review
Neurogenesis in the adult brain, a process once thought to be essentially absent, has now been demonstrated to occur throughout adult mammalian life within several brain regions. Adult neurogenesis normally occurs only within the subventricular zone (SVZ) bordering the lateral ventricles and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG). Neurogenic progenitors within these regions produce distinct neuron types, with progenitors in the SGZ giving rise to glutamatergic neurons that populate the DG granule cell layer and those within the SVZ producing neurons destined for the olfactory bulb. In this review, we highlight recent research on transcription factor expression and function during adult hippocampal neurogenesis. In this regard, recent evidence indicates that adult neurogenesis replicates important aspects of progenitor cell development in the embryonic brain. Specifically, work from our laboratory and others indicates that transcription factor cascades active in progenitor cells during neurogenesis in the embryonic cerebral cortex are also activated in adult hippocampal progenitor cells, where they play an important role in determining neuronal fate and regulating progenitor cell proliferation and maintenance. These findings suggest that conserved transcription factor cascades regulate genetic programs that delineate progenitor cell lineages and control progenitor cell proliferation and differentiation.
Topics: Animals; Hippocampus; Humans; Neurogenesis; Neurons; Transcription Factors
PubMed: 21412988
DOI: 10.1002/dneu.20882 -
Neuroscience Research Sep 2022New neurons are constantly generated in the olfactory bulb and the dentate gyrus of the hippocampus. The number of new cells depends on sensory experiences; an enriched...
New neurons are constantly generated in the olfactory bulb and the dentate gyrus of the hippocampus. The number of new cells depends on sensory experiences; an enriched odor environment increases neurogenesis and neural survival. The aim of this study was to investigate whether enriched olfactory stimuli affect neurogenesis of mitral and granule cells of the olfactory bulb and dentate gyrus, and whether respiratory activity accompanied by olfactory stimuli is associated with new cells in these regions. To this end, respiratory activity during enriched odor stimuli was continuously measured in mice and new cells were stained with 5-bromo-2'-deoxyuridine, which selectively labels proliferating cells. An enriched olfactory environment significantly increased neurogenesis of mitral and granule cells in the olfactory bulb, but not in the dentate gyrus. Additionally, an increase of new granule cells under the enriched odor condition was correlated to sniffing frequency power, which had a significantly different pattern from the no-odor condition. A high respiratory frequency with frequent odor stimuli may be associated with activation of granule cells to form inhibitory neurons and this active state might increase granule cell neurogenesis.
Topics: Animals; Mice; Neurogenesis; Neurons; Odorants; Olfactory Bulb; Smell
PubMed: 35636589
DOI: 10.1016/j.neures.2022.05.007 -
Neuron May 2011While adult-born neurons in the olfactory bulb (OB) and the dentate gyrus (DG) subregion of the hippocampus have fundamentally different properties, they may have more... (Comparative Study)
Comparative Study Review
While adult-born neurons in the olfactory bulb (OB) and the dentate gyrus (DG) subregion of the hippocampus have fundamentally different properties, they may have more in common than meets the eye. Here, we propose that new granule cells in the OB and DG may function as modulators of principal neurons to influence pattern separation and that adult neurogenesis constitutes an adaptive mechanism to optimally encode contextual or olfactory information. See the related Perspective from Aimone, Deng, and Gage, "Resolving New Memories: A Critical Look at the Dentate Gyrus, Adult Neurogenesis, and Pattern Separation," in this issue of Neuron.
Topics: Animals; Cell Differentiation; Hippocampus; Humans; Nerve Net; Neurogenesis; Neurons; Olfactory Bulb
PubMed: 21609817
DOI: 10.1016/j.neuron.2011.05.012 -
Brain Structure & Function Jan 2022Brain structural features of healthy individuals are associated with olfactory functions. However, due to the pathophysiological differences, congenital and acquired...
Brain structural features of healthy individuals are associated with olfactory functions. However, due to the pathophysiological differences, congenital and acquired anosmia may exhibit different structural characteristics. A systematic review was undertaken to compare brain structural features between patients with congenital and acquired anosmia. A systematic search was conducted using PubMed/MEDLINE and Scopus electronic databases to identify eligible reports on anosmia and structural changes and reported according to PRISMA guidelines. Reports were extracted for information on demographics, psychophysical evaluation, and structural changes. Then, the report was systematically reviewed based on various aetiologies of anosmia in relation to (1) olfactory bulb, (2) olfactory sulcus, (3) grey matter (GM), and white matter (WM) changes. Twenty-eight published studies were identified. All studies reported consistent findings with strong associations between olfactory bulb volume and olfactory function across etiologies. However, the association of olfactory function with olfactory sulcus depth was inconsistent. The present study observed morphological variations in GM and WM volume in congenital and acquired anosmia. In acquired anosmia, reduced olfactory function is associated with reduced volumes and thickness involving the gyrus rectus, medial orbitofrontal cortex, anterior cingulate cortex, and cerebellum. These findings contrast to those observed in congenital anosmia, where a reduced olfactory function is associated with a larger volume and higher thickness in parts of the olfactory network, including the piriform cortex, orbitofrontal cortex, and insula. The present review proposes that the structural characteristics in congenital and acquired anosmia are altered differently. The mechanisms behind these changes are likely to be multifactorial and involve the interaction with the environment.
Topics: Anosmia; Brain; Gray Matter; Humans; Magnetic Resonance Imaging; Olfaction Disorders
PubMed: 34635958
DOI: 10.1007/s00429-021-02397-3 -
Journal of Clinical Medicine May 2023The efficacy of electroconvulsive therapy (ECT) in the treatment of adolescents with treatment-refractory depression is still unsatisfactory, and the individual...
OBJECTS
The efficacy of electroconvulsive therapy (ECT) in the treatment of adolescents with treatment-refractory depression is still unsatisfactory, and the individual differences are large. It is not clear which factors are related to the treatment effect. Resting-state fMRI may be a good tool to predict the clinical efficacy of this treatment, and it is helpful to identify the most suitable population for this treatment.
METHODS
Forty treatment-refractory depression adolescents were treated by ECT and evaluated using HAMD and BSSI scores before and after treatment, and were then divided into a treatment response group and a non-treatment group according to the reduction rate of the HAMD scale. We extracted the ALFF, fALFF, ReHo, and functional connectivity of patients as predicted features after a two-sample -test and LASSO to establish and evaluate a prediction model of ECT in adolescents with treatment-refractory depression.
RESULTS
Twenty-seven patients achieved a clinical response; symptoms of depression and suicidal ideation were significantly improved after treatment with ECT, which was reflected in a significant decrease in the scores of HAMD and BSSI ( < 0.001). The efficacy was predicted by ALFF, fALFF, ReHo, and whole-brain-based functional connectivity. We found that models built on a subset of features of ALFF in the left insula, fALFF in the left superior parietal gyrus, right superior parietal gyrus, and right angular, and functional connectivity between the left superior frontal gyrus, dorsolateral-right paracentral lobule, right middle frontal gyrus, orbital part-left cuneus, right olfactory cortex-left hippocampus, left insula-left thalamus, and left anterior cingulate gyrus-right hippocampus to have the best predictive performance (AUC > 0.8).
CONCLUSIONS
The local brain function in the insula, superior parietal gyrus, and angular gyrus as well as characteristic changes in the functional connectivity of cortical-limbic circuits may serve as potential markers for efficacy judgment of ECT and help to provide optimized individual treatment strategies for adolescents with depression and suicidal ideation in the early stages of treatment.
PubMed: 37240663
DOI: 10.3390/jcm12103556 -
Chemical Senses Jan 2022The brain forms robust associations between odors and emotionally salient memories, making odors especially effective at triggering fearful or traumatic memories. Using...
The brain forms robust associations between odors and emotionally salient memories, making odors especially effective at triggering fearful or traumatic memories. Using Pavlovian olfactory fear conditioning (OFC), a variant of the traditional tone-shock paradigm, this study explored the changes involved in its processing. We assessed the expression of neuronal plasticity markers phosphorylated cyclic adenosine monophosphate response element binding protein (pCREB) and phosphorylated mitogen-activated protein kinase (pMAPK) 24 h and 14 days following OFC, in newborn neurons (EdU+) and in brain regions associated with olfactory memory processing; the olfactory bulb, piriform cortex, amygdale, and hippocampus. Here, we show that all proliferating neurons in the dentate gyrus of the hippocampus and glomerular layer of the olfactory bulb were colocalized with pCREB at 24 h and 14 days post-conditioning, and the number of proliferating neurons at both time points were statistically similar. This suggests the occurrence of long-term potentiation within the neurons of this pathway. Finally, OFC significantly increased the density of pCREB- and pMAPK-positive immunoreactive neurons in the medial and cortical subnuclei of the amygdala and the posterior piriform cortex, suggesting their key involvement in its processing. Together, our investigation identifies changes in neuroplasticity within critical neural circuits responsible for olfactory fear memory.
Topics: Amygdala; Cell Proliferation; Fear; Humans; Infant, Newborn; Piriform Cortex; Smell
PubMed: 35997758
DOI: 10.1093/chemse/bjac021 -
The Journal of Neuroscience : the... Jan 2016Numerous clinical reports underscore the frequency of olfactory impairments in patients suffering from major depressive disorders (MDDs), yet the underlying...
UNLABELLED
Numerous clinical reports underscore the frequency of olfactory impairments in patients suffering from major depressive disorders (MDDs), yet the underlying physiopathological mechanisms remain poorly understood. We hypothesized that one key link between olfactory deficits and MDD lies in hypercortisolemia, a cardinal symptom of MDD. Corticosterone (CORT) is known to negatively correlate with hippocampal neurogenesis, yet its effects on olfactory neurogenesis and olfaction remain unknown. Here we used a rodent model of anxiety/depression-like states, which is based on chronic CORT administration and studied the effects of the antidepressant fluoxetine (FLX) on behavior, olfaction, and adult neurogenesis in the dentate gyrus (DG), olfactory bulb (OB), and the olfactory epithelium (OE). Chronic CORT had no effect on cell proliferation in the OE or on olfactory sensory neurons projecting to the OB, but induced pronounced deficits in olfactory acuity, fine discrimination of odorants and olfactory memory. These alterations were accompanied by a significant decrease in the number of adult-born neurons in both the DG and OB. Remarkably, FLX not only reversed depression-like states as expected, but also improved olfactory acuity, memory, and restored impaired adult neurogenesis. However, fine olfactory discrimination was not restored. Morphological analysis of adult-born neurons in both the DG and the OB showed that dendritic complexity was not significantly affected by CORT, but was increased by FLX. These findings demonstrate an essential role for glucocorticoids in triggering olfactory impairments in MDD and highlight a novel therapeutic effect of FLX.
SIGNIFICANCE STATEMENT
Increasing clinical reports show that major depression is characterized by pronounced olfactory deficits, yet the underlying mechanisms remain unknown. In this work, we used an endocrine model of depression to study whether hypothalamic-pituitary-adrenal axis perturbation could be sufficient to provoke olfactory impairments. We found that chronic corticosterone not only induces marked deficits in olfactory acuity, fine discrimination and olfactory memory, but also significantly decreases bulbar and hippocampal neurogenesis. Importantly, the antidepressant fluoxetine restores both adult neurogenesis and depressive states, and improves most olfactory functions. Our data reveal that impairment of hypothalamic-pituitary-adrenal axis during depression can lead to olfactory deficits and that the neurogenic effects of selective serotonin reuptake inhibitor antidepressants can successfully restore certain olfactory functions.
Topics: Animals; Anti-Inflammatory Agents; Antidepressive Agents, Second-Generation; Anxiety; Cell Proliferation; Corticosterone; Depression; Disease Models, Animal; Exploratory Behavior; Feeding Behavior; Fluoxetine; Grooming; Male; Mice; Mice, Inbred C57BL; Neurogenesis; Olfaction Disorders; Olfactory Mucosa; Olfactory Receptor Neurons; Reaction Time
PubMed: 26758842
DOI: 10.1523/JNEUROSCI.2817-15.2016 -
Frontiers in Neurology 2022Traumatic brain injury is one of the major causes of human olfactory dysfunction and leads to brain structure alterations, mainly in the cortical olfactory regions. Our...
OBJECTIVE
Traumatic brain injury is one of the major causes of human olfactory dysfunction and leads to brain structure alterations, mainly in the cortical olfactory regions. Our study aimed to investigate volume changes in the gray matter (GM) and white matter (WM) in patients with post-traumatic anosmia and then to explore the relationship between GM volume and olfactory function.
METHODS
Ethics committee approved prospective studies which included 22 patients with post-traumatic anosmia and 18 age- and gender-matched healthy volunteers. Olfactory function was assessed using the Sniffin' Sticks. High-resolution 3-dimensional T1 MRIs of the participants were acquired on a 3T scanner and the data were collected for voxel-based morphometry (VBM) analysis. Furthermore, the GM and WM volumes of the whole brain regions were compared and correlated with olfactory function.
RESULTS
The analysis revealed significant GM volume reduction in the orbitofrontal cortex (OFC), gyrus rectus (GR), olfactory cortex, insula, parahippocampal, temporal pole, and cerebellum (all < 0.001) in patients. Besides, WM volume loss was also found in the OFC, GR, and insula (all < 0.001) in patients. All WM atrophy areas were connected to areas of GM volume loss spatially. Correlation analysis showed the olfactory scores were significantly positively correlated with the GM volume of the occipital cortex ( < 0.001, and < 0.05), while no significant correlation was found between the Sniffin' Sticks test scores and the WM volume in patients.
CONCLUSION
The reduction of GM and WM volume in olfactory-related regions was responsible for olfactory dysfunction in post-traumatic patients. The occipital cortex may play a compensation mechanism to maintain the residual olfactory function. To our knowledge, we report here for the first time on white matter volume alterations specifically in post-traumatic patients with anosmia.
PubMed: 35860485
DOI: 10.3389/fneur.2022.690760 -
Neurobiology of Disease Feb 2010Neural stem cells persist in the adult mammalian forebrain and are a potential source of neurons for repair after brain injury. The two main areas of persistent... (Review)
Review
Neural stem cells persist in the adult mammalian forebrain and are a potential source of neurons for repair after brain injury. The two main areas of persistent neurogenesis, the subventricular zone (SVZ)-olfactory bulb pathway and hippocampal dentate gyrus, are stimulated by brain insults such as stroke or trauma. Here we focus on the effects of focal cerebral ischemia on SVZ neural progenitor cells in experimental stroke, and the influence of mechanical injury on adult hippocampal neurogenesis in models of traumatic brain injury (TBI). Stroke potently stimulates forebrain SVZ cell proliferation and neurogenesis. SVZ neuroblasts are induced to migrate to the injured striatum, and to a lesser extent to the peri-infarct cortex. Controversy exists as to the types of neurons that are generated in the injured striatum, and whether adult-born neurons contribute to functional restoration remains uncertain. Advances in understanding the regulation of SVZ neurogenesis in general, and stroke-induced neurogenesis in particular, may lead to improved integration and survival of adult-born neurons at sites of injury. Dentate gyrus cell proliferation and neurogenesis similarly increase after experimental TBI. However, pre-existing neuroblasts in the dentate gyrus are vulnerable to traumatic insults, which appear to stimulate neural stem cells in the SGZ to proliferate and replace them, leading to increased numbers of new granule cells. Interventions that stimulate hippocampal neurogenesis appear to improve cognitive recovery after experimental TBI. Transgenic methods to conditionally label or ablate neural stem cells are beginning to further address critical questions regarding underlying mechanisms and functional significance of neurogenesis after stroke or TBI. Future therapies should be aimed at directing appropriate neuronal replacement after ischemic or traumatic injury while suppressing aberrant integration that may contribute to co-morbidities such as epilepsy or cognitive impairment.
Topics: Animals; Brain Injuries; Brain Ischemia; Cell Proliferation; Corpus Striatum; Dentate Gyrus; Humans; Nerve Degeneration; Neurogenesis; Prosencephalon; Recovery of Function; Regeneration; Stem Cells
PubMed: 19909815
DOI: 10.1016/j.nbd.2009.11.002 -
Frontiers in Neuroscience 2016Adult neurogenesis is considered to contribute to a certain degree of plasticity for the brain. However, the effects of adult-born neurons on the brain are still largely...
Adult neurogenesis is considered to contribute to a certain degree of plasticity for the brain. However, the effects of adult-born neurons on the brain are still largely unknown. Here, we specifically altered the expression of miR-30c in the subventricular zone (SVZ) and dentate gyrus (DG) by stereotaxic injection with their respective up- and down-regulated lentiviruses. Results showed an increased level of miR-30c enhanced adult neurogenesis by prompting cell-cycles of stem cells, whereas down-regulated miR-30c led to the opposite results. When these effects of miR-30c lasted for 3 months, we detected significant morphological changes in the olfactory bulb (OB) and lineage alteration in the hippocampus. Tests of olfactory sensitivity and associative and spatial memory showed that a certain amount of adult-born neurons are essential for the normal functions of the OB and hippocampus, but there also exist redundant newborn neurons that do not further improve the functioning of these areas. Our study revealed the interactions between miRNA, adult neurogenesis, brain morphology and function, and this provides a novel insight into understanding the role of newborn neurons in the adult brain.
PubMed: 27242411
DOI: 10.3389/fnins.2016.00207