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Frontiers in Neuroanatomy 2021Galectins are β-galactoside-binding lectins consisting of 15 members in mammals. Galectin-1,-3,-4,-8, and -9 are predominantly expressed in the central nervous system... (Review)
Review
Galectins are β-galactoside-binding lectins consisting of 15 members in mammals. Galectin-1,-3,-4,-8, and -9 are predominantly expressed in the central nervous system (CNS) and regulate various physiological and pathological events. This review summarizes the current knowledge of the cellular expression and role of galectins in the CNS, and discusses their functions in neurite outgrowth, myelination, and neural stem/progenitor cell niches, as well as in ischemic/hypoxic/traumatic injuries and neurodegenerative diseases such as multiple sclerosis. Galectins are expressed in both neurons and glial cells. Galectin-1 is mainly expressed in motoneurons, whereas galectin-3-positive neurons are broadly distributed throughout the brain, especially in the hypothalamus, indicating its function in the regulation of homeostasis, stress response, and the endocrine/autonomic system. Astrocytes predominantly contain galectin-1, and galectin-3 and-9 are upregulated along with its activation. Activated, but not resting, microglia contain galectin-3, supporting its phagocytic activity. Galectin-1,-3, and -4 are characteristically expressed during oligodendrocyte differentiation. Galectin-3 from microglia promotes oligodendrocyte differentiation and myelination, while galectin-1 and axonal galectin-4 suppress its differentiation and myelination. Galectin-1- and- 3-positive cells are involved in neural stem cell niche formation in the subventricular zone and hippocampal dentate gyrus, and the migration of newly generated neurons and glial cells to the olfactory bulb or damaged lesions. In neurodegenerative diseases, galectin-1,-8, and -9 have neuroprotective and anti-inflammatory activities. Galectin-3 facilitates pro-inflammatory action; however, it also plays an important role during the recovery period. Several ligand glycoconjugates have been identified so far such as laminin, integrins, neural cell adhesion molecule L1, sulfatide, neuropilin-1/plexinA4 receptor complex, triggering receptor on myeloid cells 2, and T cell immunoglobulin and mucin domain. -glycan branching on lymphocytes and oligodendroglial progenitors mediated by β1,6--acetylglucosaminyltransferase V (Mgat5/GnTV) influences galectin-binding, modulating inflammatory responses and remyelination in neurodegenerative diseases. De-sulfated galactosaminoglycans such as keratan sulfate are potential ligands for galectins, especially galectin-3, regulating neural regeneration. Galectins have multitudinous functions depending on cell type and context as well as post-translational modifications, including oxidization, phosphorylation, S-nitrosylation, and cleavage, but there should be certain rules in the expression patterns of galectins and their ligand glycoconjugates, possibly related to glucose metabolism in cells.
PubMed: 34720894
DOI: 10.3389/fnana.2021.767330 -
Postepy Psychiatrii Neurologii Dec 2021Adult human brain neurogenesis is the process of cell division, differentiation, and integration of the new neurons in the brain. The neurons that arise in... (Review)
Review
PURPOSE
Adult human brain neurogenesis is the process of cell division, differentiation, and integration of the new neurons in the brain. The neurons that arise in subventricular zone migrate to the olfactory bulb, while the newly formed neurons in the dentate gyrus migrate locally. In adult neurogenesis starting from neural stem cells, in addition to glial neurons astrocytes and oligodendrocytes are also formed. Neurogenesis is regulated by endogenous and exogenous factors influencing the proliferation potential of progeni tor cells and accelerating the rate of development of the dendritic connections of newly formed neurons.
VIEWS
The slow, initial process of a developing neurodegenerative disease may have a stimulating effect on neurogenesis. Increased levels of pro-inflammatory factors may contribute to the formation of new neurons. A similar hypothesis seems to be confirmed by data in the literature. The importance of proneurogenic effects during inflammation is shown by proteins secreted by active microglia, mainly CD 47 and CD 55 and interleukin 4 and 10. On the other hand, the unfavorable effect of the inflammatory process in the brain is usually associated with chronic disease in it, when stimulated microglia increase the concentration of cytokines that have a negative effect on neurogenesis.
CONCLUSIONS
Restoring the balance between dying and emerging neurons is important and offers hope for new therapy directions in the treatment of neurodegenerative diseases. We note common points that could become the target of further research. Attention should be paid to disorders of the calcium metabolism, so important in signal transduction, the state of mitochondria with enzymes involved in the formation of ATP, and the reduction of inflammation in neurogenic regions.
PubMed: 37082558
DOI: 10.5114/ppn.2021.111950 -
Journal of the Neurological Sciences Jun 2016Association of changes in olfactory-related structures with olfactory function in patients with multiple sclerosis (MS) is not well understood. We used a T&T...
Association of changes in olfactory-related structures with olfactory function in patients with multiple sclerosis (MS) is not well understood. We used a T&T olfactometer test kit to evaluate olfactory function in 26 patients with MS and 26 age- and sex-matched healthy controls (HC). Then, Brain MRI were performed and olfactory-related structures were analyzed in these subjects. Olfactory detection and recognition threshold were significantly higher in the MS group, interestingly olfactory recognition threshold positively correlated with expanded disability status scale scores in these patients. Olfactory bulb (OB) volume reduced in patients with olfactory dysfunction (ODF). At the same time, reductions in gray matter (GM) volume were observed in the parahippocampal gyrus (PCG), amygdala, piriform cortex, and inferior frontal gyrus in patients with MS compared to HC. Atrophy of the PCG was more obvious in patients with ODF than patients without ODF and the PCG volume correlated with the olfactory recognition threshold, while no difference was found in fractional anisotropy values of tract-based spatial statistics analysis in the two groups. Olfactory function in patients with MS tends to become gradually more impaired with disability aggravation. Decreases in the volume of the OB and olfactory-related GM might provide valuable information about disease status in patients with MS with olfactory impairment.
Topics: Adult; Brain; Disability Evaluation; Female; Humans; Magnetic Resonance Imaging; Male; Multiple Sclerosis; Olfaction Disorders; Organ Size; Pattern Recognition, Physiological; Sensory Thresholds
PubMed: 27206870
DOI: 10.1016/j.jns.2016.03.045 -
Neuropsychologia Nov 2022Olfaction, the sense of smell, provides important behavioral functions in many species. The hippocampus (HC) is critical for identifying odors, and hippocampal volume is...
Olfaction, the sense of smell, provides important behavioral functions in many species. The hippocampus (HC) is critical for identifying odors, and hippocampal volume is associated with odor identification ability. Impaired odor identification is often reported in old age and might provide an early marker of cognitive decline and dementia. Here, we explored cross-sectional (n = 225) and longitudinal (n = 118) associations between odor identification ability and hippocampal subfield volumes in a sample of middle-aged and older persons (25-80 years). In older participants, longitudinally decreasing volumes of the hippocampal tail, subiculum, CA4 and the dentate gyrus correlated with changes in odor identification. None of these correlations were observed in younger participants, but there was a significant correlation between longitudinal volume reduction in the tail subfield of the hippocampus and odor identification change across all participants. There were no significant cross-sectional associations between hippocampal subfields and odor identification. These exploratory results provide new information regarding precisely where and when declining HC subfield volumes might be associated with odor identification.
Topics: Middle Aged; Humans; Aged; Smell; Cross-Sectional Studies; Magnetic Resonance Imaging; Hippocampus; Organ Size
PubMed: 36210600
DOI: 10.1016/j.neuropsychologia.2022.108353 -
Journal of Alzheimer's Disease : JAD 2023Alzheimer's disease (AD) is an increasingly common type of dementia. Apolipoprotein E (APOE) gene is a strong risk factor for AD.
BACKGROUND
Alzheimer's disease (AD) is an increasingly common type of dementia. Apolipoprotein E (APOE) gene is a strong risk factor for AD.
OBJECTIVE
Here, we explored alterations in grey matter structure (GMV) and networks in AD, as well as the effects of the APOEɛ4 allele on neuroimaging regions based on structural magnetic resonance imaging (sMRI).
METHODS
All subjects underwent an sMRI scan. GMV and cortical thickness were calculated using voxel-based morphological analysis, and structural networks were constructed based on graph theory analysis to compare differences between AD and normal controls.
RESULTS
The volumes of grey matter in the bilateral inferior temporal gyrus, right middle temporal gyrus, right inferior parietal lobule, right limbic lobe, right frontal lobe, left anterior cingulate gyrus, and bilateral olfactory cortex of patients with AD were significantly decreased. The cortical thickness in patients with AD was significantly reduced in the left lateral occipital lobe, inferior parietal lobe, orbitofrontal region, precuneus, superior parietal gyrus, right precentral gyrus, middle temporal gyrus, pars opercularis gyrus, insular gyrus, superior marginal gyrus, bilateral fusiform gyrus, and superior frontal gyrus. In terms of local properties, there were significant differences between the AD and control groups in these areas, including the right bank, right temporalis pole, bilateral middle temporal gyrus, right transverse temporal gyrus, left postcentral gyrus, and left parahippocampal gyrus.
CONCLUSION
There were significant differences in the morphological and structural covariate networks between AD patients and healthy controls under APOEɛ4 allele effects.
Topics: Humans; Alzheimer Disease; Apolipoprotein E4; Brain; Gray Matter; Magnetic Resonance Imaging
PubMed: 36530087
DOI: 10.3233/JAD-220877 -
Parkinsonism & Related Disorders May 2024Olfactory dysfunction and REM sleep behavior disorder (RBD) are associated with distinct cognitive trajectories in the course of Parkinson's disease (PD). The underlying...
INTRODUCTION
Olfactory dysfunction and REM sleep behavior disorder (RBD) are associated with distinct cognitive trajectories in the course of Parkinson's disease (PD). The underlying neurobiology for this relationship remains unclear but may involve distinct patterns of neurodegeneration. This study aimed to examine longitudinal cortical atrophy and thinning in early-stage PD with severe olfactory deficit (anosmia) without and with concurrent probable RBD.
METHODS
Longitudinal MRI data over four years of 134 de novo PD and 49 healthy controls (HC) from the Parkinson Progression Marker Initiative (PPMI) cohort were analyzed using a linear mixed-effects model. Patients were categorized into those with anosmia by the University of Pennsylvania Smell Identification Test (UPSIT) score ≤ 18 (AO+) and those without (UPSIT score > 18, AO-). The AO+ group was further subdivided into AO+ with probable RBD (AO+RBD+) and without (AO+RBD-) for subanalysis.
RESULTS
Compared to subjects without baseline anosmia, the AO+ group exhibited greater longitudinal declines in both volume and thickness in the bilateral parahippocampal gyri and right transverse temporal gyrus. Patients with concurrent anosmia and RBD showed more extensive longitudinal declines in cortical volume and thickness, involving additional brain regions including the bilateral precuneus, left inferior temporal gyrus, right paracentral gyrus, and right precentral gyrus.
CONCLUSIONS
The atrophy/thinning patterns in early-stage PD with severe olfactory dysfunction include regions that are critical for cognitive function and could provide a structural basis for previously reported associations between severe olfactory deficit and cognitive decline in PD. Concurrent RBD might enhance the dynamics of cortical changes.
Topics: Humans; Parkinson Disease; Male; Female; Aged; Middle Aged; Longitudinal Studies; Magnetic Resonance Imaging; REM Sleep Behavior Disorder; Olfaction Disorders; Atrophy; Anosmia; Disease Progression; Brain
PubMed: 38430690
DOI: 10.1016/j.parkreldis.2024.106072 -
Cell & Bioscience May 2023Where the gene is expressed determines the function of the gene. Neuregulin 1 (Nrg1) encodes a tropic factor and is genetically linked with several neuropsychiatry...
BACKGROUND
Where the gene is expressed determines the function of the gene. Neuregulin 1 (Nrg1) encodes a tropic factor and is genetically linked with several neuropsychiatry diseases such as schizophrenia, bipolar disorder and depression. Nrg1 has broad functions ranging from regulating neurodevelopment to neurotransmission in the nervous system. However, the expression pattern of Nrg1 at the cellular and circuit levels in rodent brain is not full addressed.
METHODS
Here we used CRISPR/Cas9 techniques to generate a knockin mouse line (Nrg1) that expresses a P2A-Cre cassette right before the stop codon of Nrg1 gene. Since Cre recombinase and Nrg1 are expressed in the same types of cells in Nrg1 mice, the Nrg1 expression pattern can be revealed through the Cre-reporting mice or adeno-associated virus (AAV) that express fluorescent proteins in a Cre-dependent way. Using unbiased stereology and fluorescence imaging, the cellular expression pattern of Nrg1 and axon projections of Nrg1-positive neurons were investigated.
RESULTS
In the olfactory bulb (OB), Nrg1 is expressed in GABAergic interneurons including periglomerular (PG) and granule cells. In the cerebral cortex, Nrg1 is mainly expressed in the pyramidal neurons of superficial layers that mediate intercortical communications. In the striatum, Nrg1 is highly expressed in the Drd1-positive medium spiny neurons (MSNs) in the shell of nucleus accumbens (NAc) that project to substantia nigra pars reticulata (SNr). In the hippocampus, Nrg1 is mainly expressed in granule neurons in the dentate gyrus and pyramidal neurons in the subiculum. The Nrg1-expressing neurons in the subiculum project to retrosplenial granular cortex (RSG) and mammillary nucleus (MM). Nrg1 is highly expressed in the median eminence (ME) of hypothalamus and Purkinje cells in the cerebellum.
CONCLUSIONS
Nrg1 is broadly expressed in mouse brain, mainly in neurons, but has unique expression patterns in different brain regions.
PubMed: 37147705
DOI: 10.1186/s13578-023-01032-4 -
Frontiers in Aging Neuroscience 2023The correlation between gut microbiota and Alzheimer's disease (AD) is increasingly being recognized by clinicians. However, knowledge about the gut-brain-cognition...
BACKGROUND
The correlation between gut microbiota and Alzheimer's disease (AD) is increasingly being recognized by clinicians. However, knowledge about the gut-brain-cognition interaction remains largely unknown.
METHODS
One hundred and twenty-seven participants, including 35 normal controls (NCs), 62 with subjective cognitive decline (SCD), and 30 with cognitive impairment (CI), were included in this study. The participants underwent neuropsychological assessments and fecal microbiota analysis through 16S ribosomal RNA (rRNA) Illumina Miseq sequencing technique. Structural MRI data were analyzed for cortical anatomical features, including thickness, sulcus depth, fractal dimension, and Toro's gyrification index using the SBM method. The association of altered gut microbiota among the three groups with structural MRI metrics and cognitive function was evaluated. Furthermore, co-expression network analysis was conducted to investigate the gut-brain-cognition interactions.
RESULTS
The abundance of , and decreased with cognitive ability. , and were specifically enriched in the CI group. abundance was correlated with changes in brain gray matter and cerebrospinal fluid volume ( = 0.0214, = 0.0162) and significantly with changes in cortical structures in brain regions, such as the internal olfactory area and the parahippocampal gyrus. The three colonies enriched in the CI group were positively correlated with cognitive function and significantly associated with changes in cortical structure related to cognitive function, such as the precuneus and syrinx gyrus.
CONCLUSION
This study provided evidence that there was an inner relationship among the altered gut microbiota, brain atrophy, and cognitive decline. Targeting the gut microbiota may be a novel therapeutic strategy for early AD.
PubMed: 37520126
DOI: 10.3389/fnagi.2023.1216509 -
ORL; Journal For Oto-rhino-laryngology... 2019A number of patients with a diminished sense of smell also can suffer from parosmia. These patients with such a qualitative smell disorder are often more severely...
INTRODUCTION
A number of patients with a diminished sense of smell also can suffer from parosmia. These patients with such a qualitative smell disorder are often more severely affected than patients exhibiting only a quantitative smell disorder. Qualitative smell disorders have heretofore been poorly investigated. The focus of the present study was, using functional MRI, to compare the central processing of olfactory stimulation in patients with qualitative smell disorders.
MATERIAL AND METHODS
A total of 23 patients were investigated, 12 hyposmic patients without parosmia (HYP group) and 11 hyposmic patients with parosmia (PAR group). Both groups were matched with regard to sex and age. The olfactory smells used were peach and coffee odors.
RESULTS
The two groups exhibited different patterns of activation. In HYP patients a stronger activation was observed in the medial orbitofrontal cortex, anterior cingulate cortex, and parahippocampal gyrus, whereas in the PAR group stronger activation in the thalamus and putamen was seen.
DISCUSSION
These results are consistent with the hypothesis that there are specific patterns in the central processing of olfactory stimuli which differ in hyposmic patients with and without parosmia.
Topics: Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Olfaction Disorders; Olfactory Cortex; Reproducibility of Results; Smell
PubMed: 31238309
DOI: 10.1159/000500558 -
NeuroImage. Clinical 2022Subjective cognitive decline (SCD), one of the important clinical indicators for preclinical Alzheimer's disease (AD), is primarily defined as self-perceived cognitive...
BACKGROUNDS
Subjective cognitive decline (SCD), one of the important clinical indicators for preclinical Alzheimer's disease (AD), is primarily defined as self-perceived cognitive decline without objective evidence for cognitive impairment. However, the accuracy of their self-evaluation of cognition is unclear. This study sought to investigate the capacity for self-evaluation of own cognitive performance in SCD by applying an objective metamemory paradigm.
METHODS
147 individuals with SCD were classified into four subgroups by their subjective feeling of worse performance than peers or not (P+/-) and whether they have objectively slight cognitive impairment compared to normative data (S+/-). Metamemory scores, the amplitude of the low-frequency fluctuation (ALFF), fractional low-frequency fluctuation amplitude (fALFF), and cortical thickness were compared among four subgroups. Partial correlations between neuropsychological scores and neuroimaging measures were examined, controlling for age, sex, and education years.
RESULTS
SCD S+P- showed the worst performance in short-term delayed recall and the worst metamemory performance, indicated by the highest value in the degree of confidence of short-term delayed recall (DOC-N4) and long-term cued recall (DOC-N6) and the worst value in relative accuracy of judgments of short-term delayed recall (ROJ-N4). ALFF values in the bilateral superior medial frontal and olfactory cortices and the left superior orbitofrontal gyrus cortex were significantly higher in SCD P- compared with SCD P+ groups (all P < 0.05, FWE-corrected, cluster-wise level). A significant S × P interaction effect in the left hippocampus and middle cingulate cortex was found for the fALFF signals (all P < 0.05, FWE-corrected, cluster-wise level). Significant interaction and main effects on cortical thickness were reported. The parahippocampal and posterior cingulate cortices were significantly decreased in SCD S+P- (all P < 0.05).
CONCLUSION
SCD S+P- showed the worst episodic memory performance, altered metamemory capacity (overconfidence and less accuracy of judgment), and altered neuroimaging measures, though they had feelings of similar performance with peers. Our results indicate that metamemory capacity is affected in a subtype of SCD with reduced cortical thickness and intensity of regional spontaneous activity in key areas for metamemory processing.
Topics: Humans; Neuropsychological Tests; Magnetic Resonance Imaging; Cognitive Dysfunction; Cognition; Metacognition
PubMed: 36451360
DOI: 10.1016/j.nicl.2022.103255