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Cellular and Molecular Life Sciences :... Jul 2012Neurogenesis, the production of new neurons, occurs in two specialized niches in the adult brain, the subgranular zone (SGZ) of the dentate gyrus and the subventricular... (Review)
Review
Neurogenesis, the production of new neurons, occurs in two specialized niches in the adult brain, the subgranular zone (SGZ) of the dentate gyrus and the subventricular zone (SVZ) adjacent to the lateral ventricles. In the SGZ, neural stem cells (NSCs) give rise to glutamatergic granule neurons that integrate into the granule cell layer. In the SVZ, NSCs generate a more diverse cohort of new neurons, including GABAergic, dopaminergic, and glutamatergic neurons, all of which migrate to the olfactory bulb through the rostral migratory stream. In both adult neurogenic niches, specific transcription factors have been shown to direct fate specification and lineage commitment. This review summarizes current progress on the transcriptional control of glutamatergic neurogenesis in the SGZ and SVZ, highlighting commonalities as well as differences in their transcriptional programs. In particular, we focus on work from our laboratory and others indicating that precise, sequential expression of transcription factors regulates the progression from NSC to lineage-committed progenitor, and ultimately regulates the production and differentiation of adult-born glutamatergic neurons.
Topics: Adult; Cell Differentiation; Dentate Gyrus; Gene Expression Regulation; Humans; Models, Biological; Neural Stem Cells; Neurogenesis; Receptors, Glutamate; Transcription Factors
PubMed: 22249196
DOI: 10.1007/s00018-011-0916-y -
Brain : a Journal of Neurology Aug 2019Generalized convulsive status epilepticus is a life-threatening emergency, because recurrent convulsions can cause death or injury. A common form of generalized...
Generalized convulsive status epilepticus is a life-threatening emergency, because recurrent convulsions can cause death or injury. A common form of generalized convulsive status epilepticus is of focal onset. The neuronal circuits activated during seizure spread from the hippocampus, a frequent site of seizure origin, to the bilateral motor cortex, which mediates convulsive seizures, have not been delineated. Status epilepticus was initiated by electrical stimulation of the hippocampus. Neurons transiently activated during seizures were labelled with tdTomato and then imaged following brain slice clearing. Hippocampus was active throughout the episode of status epilepticus. Neuronal activation was observed in hippocampus parahippocampal structures: subiculum, entorhinal cortex and perirhinal cortex, septum, and olfactory system in the initial phase status epilepticus. The tdTomato-labelled neurons occupied larger volumes of the brain as seizures progressed and at the peak of status epilepticus, motor and somatosensory cortex, retrosplenial cortex, and insular cortex also contained tdTomato-labelled neurons. In addition, motor thalamic nuclei such as anterior and ventromedial, midline, reticular, and posterior thalamic nuclei were also activated. Furthermore, circuits proposed to be crucial for systems consolidation of memory: entorhinal cortex, retrosplenial cortex, cingulate gyrus, midline thalamic nuclei and prefrontal cortex were intensely active during periods of generalized tonic-clonic seizures. As the episode of status epilepticus waned, smaller volume of brain was activated. These studies suggested that seizure spread could have occurred via canonical thalamocortical pathway and many cortical structures involved in memory consolidation. These studies may help explain retrograde amnesia following seizures.
Topics: Amnesia, Retrograde; Animals; Brain; Brain Mapping; Cerebral Cortex; Electroshock; Genes, Reporter; Hippocampus; Memory Consolidation; Mice; Neural Pathways; Neurons; Olfactory Bulb; Seizures; Single-Blind Method; Status Epilepticus; Thalamic Nuclei
PubMed: 31237945
DOI: 10.1093/brain/awz170 -
Brain Sciences Apr 2023Alzheimer's disease (AD) is associated with the abnormal connection of functional networks. Olfactory impairment occurs in early AD; therefore, exploring alterations in...
Alzheimer's disease (AD) is associated with the abnormal connection of functional networks. Olfactory impairment occurs in early AD; therefore, exploring alterations in olfactory-related regions is useful for early AD diagnosis. We combined the graph theory of local brain network topology with olfactory performance to analyze the differences in AD brain network characteristics. A total of 23 patients with AD and 18 normal controls were recruited for resting-state functional magnetic resonance imaging (fMRI), clinical neuropsychological examinations and the University of Pennsylvania Smell Identification Test (UPSIT). Between-group differences in the topological properties of the local network were compared. Pearson correlations were explored based on differential brain regions and olfactory performance. Statistical analysis revealed a correlation of the degree of cognitive impairment with olfactory recognition function. Local node topological properties were significantly altered in many local brain regions in the AD group. The nodal clustering coefficients of the bilateral temporal pole: middle temporal gyrus (TPOmid), degree centrality of the left insula (INS.L), degree centrality of the right middle temporal gyrus (MTG.R), and betweenness centrality of the left middle temporal gyrus (MTG.L) were related to olfactory performance. Alterations in local topological properties combined with the olfactory impairment can allow early identification of abnormal olfactory-related regions, facilitating early AD screening.
PubMed: 37190596
DOI: 10.3390/brainsci13040631 -
European Journal of Nuclear Medicine... May 2022Hyposmia is a common feature of COVID-19 and Parkinson's disease (PD). As parkinsonism has been reported after COVID-19, a link has been hypothesized between SARS-CoV2...
PURPOSE
Hyposmia is a common feature of COVID-19 and Parkinson's disease (PD). As parkinsonism has been reported after COVID-19, a link has been hypothesized between SARS-CoV2 infection and PD. We aimed to evaluate brain metabolic correlates of isolated persistent hyposmia after mild-to-moderate COVID-19 and to compare them with metabolic signature of hyposmia in drug-naïve PD patients.
METHODS
Forty-four patients who experienced hyposmia after SARS-COV2 infection underwent brain [F]-FDG PET in the first 6 months after recovery. Olfaction was assessed by means of the 16-item "Sniffin' Sticks" test and patients were classified as with or without persistent hyposmia (COVID-hyposmia and COVID-no-hyposmia respectively). Brain [F]-FDG PET of post-COVID subgroups were compared in SPM12. COVID-hyposmia patients were also compared with eighty-two drug-naïve PD patients with hyposmia. Multiple regression analysis was used to identify correlations between olfactory test scores and brain metabolism in patients' subgroups.
RESULTS
COVID-hyposmia patients (n = 21) exhibited significant hypometabolism in the bilateral gyrus rectus and orbitofrontal cortex with respect to COVID-non-hyposmia (n = 23) (p < 0.002) and in middle and superior temporal gyri, medial/middle frontal gyri, and right insula with respect to PD-hyposmia (p < 0.012). With respect to COVID-hyposmia, PD-hyposmia patients showed hypometabolism in inferior/middle occipital gyri and cuneus bilaterally. Olfactory test scores were directly correlated with metabolism in bilateral rectus and medial frontal gyri and in the right middle temporal and anterior cingulate gyri in COVID-hyposmia patients (p < 0.006) and with bilateral cuneus/precuneus and left lateral occipital cortex in PD-hyposmia patients (p < 0.004).
CONCLUSION
Metabolic signature of persistent hyposmia after COVID-19 encompasses cortical regions involved in olfactory perception and does not overlap metabolic correlates of hyposmia in PD.
Topics: Anosmia; COVID-19; Fluorodeoxyglucose F18; Humans; Olfaction Disorders; Parkinson Disease; RNA, Viral; SARS-CoV-2; Smell
PubMed: 34984501
DOI: 10.1007/s00259-021-05666-9 -
Basic and Clinical Neuroscience 2022Addiction is a mental disorder that has many adverse effects on brain health. It alters brain structure and deteriorates brain functionality. Impairment of brain...
INTRODUCTION
Addiction is a mental disorder that has many adverse effects on brain health. It alters brain structure and deteriorates brain functionality. Impairment of brain cognition in drug addiction is illustrated in many previous works; however, olfactory perception in addiction and, in particular, its neuronal mechanisms have rarely been studied.
METHODS
In this experiment, we recruited 20 heroin addicts and 20 normal controls of the same sex, age, handedness, and socioeconomic status and compared their brain function while perceiving non-craving odors during the functional magnetic resonance imaging (fMRI). We intended to define the default olfactory system performance in addicts compared to healthy people.
RESULTS
Our study showed an overall larger activation in addicts when processing olfactory stimuli. In particular, and when comparing the two groups, the right anterior cingulate and right superior frontal gyrus had higher activations than normal, whereas the left lingual gyrus and left cerebellum showed stronger activations in the addicts.
CONCLUSION
The result of this study can unveil the missing components in addiction brain circuitry. This information is helpful in better understanding the neural mechanisms of addiction and may be advantageous in designing programs for addiction prevention or clinical treatment.
HIGHLIGHTS
Addiction is a mental disorder with cognitive, clinical, and social adverse effects.Drugs affect the functional brain networks by altering the level of neurotransmitters or by over-exciting the brain's reward system.Addiction could be in the form of drug dependency or behaviors.
PLAIN LANGUAGE SUMMARY
Addiction is a mental disorder that has many adverse effects on brain. It alters brain structure and deteriorates brain functionality. Impairment of brain cognition in many previous works. We intended to define the default olfactory system performance in addicts compared to healthy people. Our study showed an overall larger activation in addicts when processing olfactory stimuli. In particular, and when comparing the two groups, the right anterior cingulate and right superior frontal gyrus had higher activations than normal, whereas the left lingual gyrus and left cerebellum showed stronger activations in the addicts. Addiction could be in the form of drug dependency or behaviors such as gambling or gaming. Addictive disorders is so vast that sometimes an impulse control disorder, such as pathologic gambling, could also be included.
PubMed: 36425954
DOI: 10.32598/bcn.12.6.2210.1 -
Frontiers in Neuroscience 2023Experiencing chronic stress significantly increases the risk for depression. Depression is a complex disorder with varied symptoms across patients. However, feeling of...
Experiencing chronic stress significantly increases the risk for depression. Depression is a complex disorder with varied symptoms across patients. However, feeling of sadness and decreased motivation, and diminished feeling of pleasure (anhedonia) appear to be core to most depressive pathology. Odorants are potent signals that serve a critical role in social interactions, avoiding danger, and consummatory behaviors. Diminished quality of olfactory function is associated with negative effects on quality of life leading to and aggravating the symptoms of depression. Odor hedonic value (I like or I dislike this smell) is a dominant feature of olfaction and guides approach or avoidance behavior of the odor source. The neural representation of the hedonic value of odorants is carried by the granule cells in the olfactory bulb, which functions to modulate the cortical relay of olfactory information. The granule cells of the olfactory bulb and those of the dentate gyrus are the two major populations of cells in the adult brain with continued neurogenesis into adulthood. In hippocampus, decreased neurogenesis has been linked to development or maintenance of depression symptoms. Here, we hypothesize that chronic mild stress can alter olfactory hedonics through effects on the olfactory bulb neurogenesis, contributing to the broader anhedonia phenotype in stress-associated depression. To test this, mice were subjected to chronic unpredictable mild stress and then tested on measures of depressive-like behaviors, odor hedonics, and measures of olfactory neurogenesis. Chronic unpredictable mild stress led to a selective effect on odor hedonics, diminishing attraction to pleasant but not unpleasant odorants, an effect that was accompanied by a specific decrease in adult neurogenesis and of the percentage of adult-born cells responding to pleasant odorants in the olfactory bulb.
PubMed: 37600017
DOI: 10.3389/fnins.2023.1224941 -
Acta Radiologica (Stockholm, Sweden :... Sep 2022Coronaviruses may lead to invasion of the central nervous system.
BACKGROUND
Coronaviruses may lead to invasion of the central nervous system.
PURPOSE
To investigate the effects of COVID-19 infection on smell using cranial magnetic resonance imaging (MRI).
MATERIAL AND METHODS
Cranial MRI scans of 23 patients with COVID-19 (patient group [PG]) and 23 healthy controls (HCs) were evaluated. Peripheric (olfactory bulb [OB] volume and olfactory sulcus [OS] depth) and central (insular gyrus and corpus amygdala areas) smell regions were measured.
RESULTS
Smell loss was present in nine patients (39.1%) in the PG. The means of the disease duration and antiviral treatment were 3.00 ± 2.35 and 5.65 ± 1.72 days, respectively. OB volumes of the PG were significantly lower than those of the HCs bilaterally. However, no significant differences were observed between the OS depth, insular gyrus, and corpus amygdala areas of both groups. The left corpus amygdala areas were both increased with the increased disease ( = 0.035, r = 0.442) and treatment durations ( = 0.037, r = 0.438). In the PG, longer treatment duration, increase in C-reactive protein (CRP), lymphocyte count decrease, and positive thoracic computed tomography (CT) involvement were related to OS depth decrease. Right corpus amygdala areas increased in patients with COVID-19 with increased D-dimer values, and thoracic CT involvement was detected.
CONCLUSION
COVID-19 disease affects the peripheric smell region of OBs and does not affect the central smell regions of the insular gyrus and corpus amygdala areas. The importance of our study is to detect MRI findings in patients with COVID-19 leading to odor disorders. These findings may help in diagnosing the disease at an early stage.
Topics: COVID-19; Humans; Magnetic Resonance Imaging; Olfaction Disorders; Olfactory Bulb; Smell
PubMed: 34282630
DOI: 10.1177/02841851211034043 -
Translational Psychiatry Mar 2021Early detection of patients with late-life depression (LLD) with a high risk of developing dementia contributes to early intervention. Odor identification (OI)...
Early detection of patients with late-life depression (LLD) with a high risk of developing dementia contributes to early intervention. Odor identification (OI) dysfunction serves as a marker for predicting dementia, but whether OI dysfunction increases the risk of dementia in LLD patients remains unclear. The present study aimed to explore the interactive effect of LLD and OI dysfunction on the risk of dementia and its underlying neuroimaging changes. One hundred and fifty-seven LLD patients and 101 normal controls were recruited, and data on their OI, cognition, activity of daily living (ADL), and resting-state functional magnetic resonance imaging were collected. Two × two factorial analyses were used to analyze the interactive effects of LLD and OI dysfunction on neuropsychological and neuroimaging abnormalities. Mediation analyses were used to explore whether abnormalities detected by neuroimaging mediated the the associations between OI and cognition/ADL. The results suggested that LLD and OI dysfunction exhibited additive effects on reduced ADL, global cognition and memory scores, as well as neuroimaging variables including (i) increased fractional amplitude of low-frequency fluctuation (fALFF) in the right orbitofrontal cortex and right precentral cortex, and (ii) increased regional homogeneity (ReHo) in the left hippocampus/fusiform gyrus, etc. In addition, these increased fALFF and ReHo values were associated with reduced neuropsychological scores (ADL, global cognition, memory, and language). Moreover, ReHo of the left hippocampus/fusiform gyrus completely mediated the relationship between OI and ADL, and partially mediated the relationship between OI and global cognition. Overall, mediated by the hypersynchronization of the left hippocampus/fusiform gyrus, OI dysfunction may increase the risk of dementia in LLD patients.
Topics: Brain; Dementia; Depression; Hippocampus; Humans; Magnetic Resonance Imaging; Olfaction Disorders; Temporal Lobe
PubMed: 33731679
DOI: 10.1038/s41398-021-01291-0 -
Frontiers in Human Neuroscience 2022: It has been reported that type 2 diabetes (T2DM) is associated with olfactory identification (OI) impairments and cognitive decline. However, the relationship between...
: It has been reported that type 2 diabetes (T2DM) is associated with olfactory identification (OI) impairments and cognitive decline. However, the relationship between OI impairments and cognitive decline is largely unknown in T2DM patients. : Sixty-eight T2DM patients and 68 healthy controls underwent 3D-T1 MRI scans, olfactory and cognitive assessments. The cortical thickness of olfaction-related brain regions, olfactory and cognitive scores were compared between groups. Correlation analyses were carried out among cognition, olfaction, and cortical thickness of olfaction-related brain regions. : First, the cognitive and olfactory test scores of T2DM patients were lower than healthy subjects. Second, higher olfactory scores were associated with increased cortical thickness in the left parahippocampal gyrus and bilateral insula in T2DM. Third, higher olfactory scores were associated with higher cognitive performance in T2DM. Fourth, some cognitive performances were related to cortical thickness in the left parahippocampal gyrus and left insula in T2DM. : These findings indicated that olfactory dysfunction may be useful for future applications that attempt to predict cognitive decline or develop tailored therapies in T2DM patients.
PubMed: 35237139
DOI: 10.3389/fnhum.2022.773309 -
The Journal of Neuroscience : the... Dec 2021Neural oscillations can couple networks of brain regions, especially at lower frequencies. The nasal respiratory rhythm, which elicits robust olfactory bulb...
Neural oscillations can couple networks of brain regions, especially at lower frequencies. The nasal respiratory rhythm, which elicits robust olfactory bulb oscillations, has been linked to episodic memory, locomotion, and exploration, along with widespread oscillatory coherence. The piriform cortex is implicated in propagating the olfactory-bulb-driven respiratory rhythm, but this has not been tested explicitly in the context of both hippocampal theta and nasal respiratory rhythm during exploratory behaviors. We investigated systemwide interactions during foraging behavior, which engages respiratory and theta rhythms. Local field potentials from the olfactory bulb, piriform cortex, dentate gyrus, and CA1 of hippocampus, primary visual cortex, and nasal respiration were recorded simultaneously from male rats. We compared interactions among these areas while rats foraged using either visual or olfactory spatial cues. We found high coherence during foraging compared with home cage activity in two frequency bands that matched slow and fast respiratory rates. Piriform cortex and hippocampus maintained strong coupling at theta frequency during periods of slow respiration, whereas other pairs showed coupling only at the fast respiratory frequency. Directional analysis shows that the modality of spatial cues was matched to larger influences in the network by the respective primary sensory area. Respiratory and theta rhythms also coupled to faster oscillations in primary sensory and hippocampal areas. These data provide the first evidence of widespread interactions among nasal respiration, olfactory bulb, piriform cortex, and hippocampus in awake freely moving rats, and support the piriform cortex as an integrator of respiratory and theta activity. Recent studies have shown widespread interactions between the nasally driven respiratory rhythm and neural oscillations in hippocampus and neocortex. With this study, we address how the respiratory rhythm interacts with ongoing slow brain rhythms across olfactory, hippocampal, and visual systems in freely moving rats. Patterns of network connectivity change with behavioral state, with stronger interactions at fast and slow respiratory frequencies during foraging as compared with home cage activity. Routing of interactions between sensory cortices depends on the modality of spatial cues present during foraging. Functional connectivity and cross-frequency coupling analyses suggest strong bidirectional interactions between olfactory and hippocampal systems related to respiration and point to the piriform cortex as a key area for mediating respiratory and theta rhythms.
Topics: Animals; Cues; Exploratory Behavior; Male; Olfactory Perception; Piriform Cortex; Rats; Rats, Long-Evans; Respiratory Physiological Phenomena; Spatial Behavior; Theta Rhythm; Visual Perception
PubMed: 34667070
DOI: 10.1523/JNEUROSCI.0719-21.2021