Neuroanatomical, sensorimotor and cognitive deficits in adult rats with white matter injury following prenatal ischemia.
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ABSTRACT:
SUBMITTER: Delcour M
PROVIDER: S-EPMC8028965 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveExposing a pregnant female to stress during the critical period of embryonic fetal brain development increases the risk of psychiatric disorders in the offspring. The objective of this study was to investigate the effect of antidepressant tianeptine on prenatally stressed (PNS) rats.MethodsIn this study, a repeated variable stress paradigm was applied to pregnant rats during the last week of gestation. To investigate the effects of antidepressant tianeptine on PNS rats, behavioral and protein expression analyses were performed. Forced swim test, open field test, and social interaction test were performed to determine changes in PNS rats compared to non-stressed offspring. Haloperidol was used as a positive control as an antipsychotic drug based on previous studies.ResultsBehavioral changes were restored after treatment with tianeptine or haloperidol. Western blot and immunohistochemical analyses of the prefrontal cortex revealed downregulation of several neurodevelopmental proteins in PNS rats. After treatment with tianeptine or haloperidol, their expression levels were increased.ConclusionDownregulation of several proteins in PNS rats might have caused subsequent behavioral changes in PNS rats. After tianeptine or haloperidol treatment, behavioral changes in PNS rats were restored. Therefore, tianeptine might decrease incidence of prenatal stress related-psychiatric disorders such as depression and schizophrenia.
| S-EPMC5953020 | biostudies-literature
Project description:Background and Purpose- Type 2 diabetes mellitus (T2DM) is a major comorbidity that exacerbates ischemic brain injury and worsens functional outcome after stroke. T2DM is known to aggravate white matter (WM) impairment, but the underlying mechanism is not completely understood. This study was designed to test the hypothesis that T2DM impedes poststroke WM recovery by suppressing both oligodendrogenesis and beneficial microglia/macrophage responses. Methods- Permanent distal middle cerebral artery occlusion was performed in wild-type, homozygous diabetic db/db, and heterozygous db/+ mice. The adhesive removal, open field, and Morris water maze tests were used to assess neurobehavioral outcomes. Neuronal tissue loss, WM damage, oligodendrogenesis, and microglia/macrophage responses were evaluated up to 35 days after stroke. The functional integrity of WM was measured by electrophysiology. Primary microglia-oligodendrocyte cocultures were used for additional mechanistic studies. Results- T2DM exacerbated structural damage and impaired conduction of compound action potentials in WM 35 days after stroke. The deterioration in WM integrity correlated with poor sensorimotor performance. Furthermore, T2DM impaired the proliferation of oligodendrocyte precursor cells and the generation of new myelinating oligodendrocytes. T2DM also promoted a shift of microglia/macrophage phenotype toward the proinflammatory modality. Coculture studies confirmed that microglia/macrophage polarization toward the proinflammatory phenotype under high glucose conditions suppressed oligodendrocyte precursor cell differentiation. Conclusions- Deterioration of WM integrity and impairments in oligodendrogenesis after stroke are associated with poor long-term functional outcomes in experimental diabetes mellitus. High glucose concentrations may shift microglia/macrophage polarization toward a proinflammatory phenotype, significantly impairing oligodendrocyte precursor cell differentiation and WM repair.
| S-EPMC6205761 | biostudies-literature
Project description:Small white-matter infarcts of the internal capsule are clinically prevalent but underrepresented among currently available animal models of ischemic stroke. In particular, the assessment of long-term outcome, a primary end point in clinical practice, has been challenging due to mild deficits and the rapid and often complete recovery in most experimental models. We, therefore, sought to develop a focal white-matter infarction model that can mimic the lasting neurologic deficits commonly observed in stroke patients. The potent vasoconstrictor endothelin-1 (n=24) or vehicle (n=9) was stereotactically injected into the internal capsule at one of three antero-posterior levels (1, 2, or 3 mm posterior to bregma) in male Sprague-Dawley rats. Endothelin-injected animals showed highly focal (~1 mm(3)) and reproducible ischemic infarcts, with severe axonal and myelin loss accompanied by cellular infiltration when examined 2 and 4 weeks after injection. Only those rats injected with endothelin-1 at the most posterior location developed robust and pure-motor deficits in adhesive removal, cylinder and foot-fault tests that persisted at 1 month, without detectable sensory impairments. In summary, we present an internal capsule stroke model optimized to produce lasting pure-motor deficits in rats that may be suitable to study neurologic recovery and rehabilitation after white-matter injury.
| S-EPMC4640262 | biostudies-other
Project description:The rehabilitation of motor deficits following stroke relies on both sensorimotor and cognitive abilities, thereby involving large-scale brain networks. However, few studies have investigated the integration between motor and cognitive domains, as well as its neuroanatomical basis. In this retrospective study, upper limb motor responsiveness to technology-based rehabilitation was examined in a sample of 29 stroke patients (18 with right and 11 with left brain damage). Pretreatment sensorimotor and attentional abilities were found to influence motor recovery. Training responsiveness increased as a function of the severity of motor deficits, whereas spared attentional abilities, especially visuospatial attention, supported motor improvements. Neuroanatomical analysis of structural lesions and white matter disconnections showed that the poststroke motor performance was associated with putamen, insula, corticospinal tract, and frontoparietal connectivity. Motor rehabilitation outcome was mainly associated with the superior longitudinal fasciculus and partial involvement of the corpus callosum. The latter findings support the hypothesis that motor recovery engages large-scale brain networks that involve cognitive abilities and provides insight into stroke rehabilitation strategies.
| S-EPMC8035034 | biostudies-literature
Project description:Preterm birth is a principal cause of neurological disability later in life, including cognitive and behavioral deficits. Notably, cognitive impairment has greater impact on quality of life than physical disability. Survivors of preterm birth commonly have deficits of executive function. Difficulties with tasks and planning complexity correlate positively with increasing disability. To overcome these barriers for children born preterm, preclinical and clinical studies have emphasized the importance of neurorestoration. Erythropoietin (EPO) is a endogenous cytokine with multiple beneficial mechanisms of action following perinatal brain injury. While most preclinical investigations have focused on pathology and molecular mechanisms, translational studies of repair using clinically viable biobehavioral biomarkers are still lacking. Here, using an established model of encephalopathy of prematurity secondary to placental insufficiency, we tested the hypothesis that administration of EPO in the neonatal period would attenuate deficits in recognition memory and cognitive flexibility in adult rats of both sexes. We assessed cognition and executive function in two ways. First, using the classic test of novel object recognition and second, using a touchscreen platform. Touchscreen testing allows for rigorous testing of cognition and executive function in preclinical and clinical scenarios. Data show that adult rats exhibit deficits in recognition memory and cognitive flexibility following in utero placental insufficiency. Notably, neonatal treatment of EPO attenuates these deficits in adulthood and facilitates functional repair. Together, these data validate EPO neurorestoration using a clinically relevant outcome measure and support the concept that postnatal treatment following in utero injury can improve cognition and executive function through adulthood.
| S-EPMC10097461 | biostudies-literature
Project description:Myotonic dystrophy type 1 (DM1) is a genetic disorder caused by a (CTG) expansion in the DM protein kinase (DMPK) gene, representing the most common adult muscular dystrophy, characterized by a multisystem involvement with predominantly skeletal muscle and brain affection. Neuroimaging studies showed widespread white matter changes and brain atrophy in DM1, but only a few studies investigated the role of white matter metabolism in the pathophysiology of central nervous system impairment. We aim to reveal the relationship between the metabolic profile of parieto-occipital white matter (POWM) as evaluated with proton MR spectroscopy technique, with the visuoperceptual and visuoconstructional dysfunctions in DM1 patients. MR spectroscopy (3 Tesla) and neuropsychological evaluations were performed in 34 DM1 patients (19 F, age: 46.4 ± 12.1 years, disease duration: 18.7 ± 11.6 years). The content of neuro-axonal marker N-acetyl-aspartate, both relative to Creatine (NAA/Cr) and to myo-Inositol (NAA/mI) resulted significantly lower in DM1 patients compared to HC (p-values < 0.0001). NAA/Cr and NAA/mI correlated with the copy of the Rey-Osterrieth complex figure (r = 0.366, p = 0.033; r = 0.401, p = 0.019, respectively) and with Street's completion tests scores (r = 0.409, p = 0.016; r = 0.341, p = 0.048 respectively). The proportion of white matter hyperintensities within the MR spectroscopy voxel did not correlate with the metabolite content. In this study, POWM metabolic alterations in DM1 patients were not associated with the white matter morphological changes and correlated with specific neuropsychological deficits.
| S-EPMC9600392 | biostudies-literature
Project description:IntroductionIndividuals with persistent developmental stuttering display deficits in aligning motor actions to external cues (i.e., sensorimotor synchronization). Diffusion imaging studies point to stuttering-associated differences in dorsal, not ventral, white matter pathways, and in the cerebellar peduncles. Here, we studied microstructural white matter differences between adults who stutter (AWS) and fluent speakers using two complementary approaches to: (a) assess previously reported group differences in white matter diffusivity, and (b) evaluate the relationship between white matter diffusivity and sensorimotor synchronization in each group.MethodsParticipants completed a sensorimotor synchronization task and a diffusion MRI scan. We identified the cerebellar peduncles and major dorsal- and ventral-stream language pathways in each individual and assessed correlations between sensorimotor synchronization and diffusion measures along the tracts.ResultsThe results demonstrated group differences in dorsal, not ventral, language tracts, in alignment with prior reports. Specifically, AWS had significantly lower fractional anisotropy (FA) in the left arcuate fasciculus, and significantly higher mean diffusivity (MD) in the bilateral frontal aslant tract compared to fluent speakers, while no significant group difference was detected in the inferior fronto-occipital fasciculus. We also found significant group differences in both FA and MD of the left middle cerebellar peduncle. Comparing patterns of association with sensorimotor synchronization revealed a novel double dissociation: MD within the left inferior cerebellar peduncle was significantly correlated with mean asynchrony in AWS but not in fluent speakers, while FA within the left arcuate fasciculus was significantly correlated with mean asynchrony in fluent speakers, but not in AWS.ConclusionsOur results support the view that stuttering involves altered connectivity in dorsal tracts and that AWS may rely more heavily on cerebellar tracts to process timing information. Evaluating microstructural associations with sensitive behavioral measures provides a powerful tool for discovering additional functional differences in the underlying connectivity in AWS.
| S-EPMC8821245 | biostudies-literature
Project description:Diffusion tensor imaging (DTI) studies in 22q11.2 deletion syndrome (22q11DS), a neurogenetic condition associated with psychosis, report brain white matter (WM) microstructure aberrations. Several studies report that WM disruptions in 22q11DS are similar to deficits in idiopathic schizophrenia. Yet, DTI results in 22q11DS are inconsistent. We used DTI to compare WM structure in 22q11DS individuals to healthy controls (HC) and explored WM differences in 22q11DS with (+) and without (-) psychosis spectrum symptoms. We examined 39 22q11DS individuals and 39 age, sex and race equivalent HC. DTI was performed at 3T using a 64-direction protocol. Fractional anisotropy (FA) was lower, while radial diffusivity was higher in 22q11DS within the cingulum bundle. Mean diffusivity was lower in the inferior longitudinal fasciculus, while axial diffusivity (AD) was lower in the cingulum bundle, forceps major, and several posterior to anterior fasciculi. 22q11DS+ had lower FA in the cingulum bundle and lower AD in the uncinate fasciculus compared to 22q11DS-. Overall, we found aberrant WM microstructure in individuals with 22q11DS compared to age and sex matched HC and exploratory analysis indicated subtle WM deficits associated with psychosis. The findings highlight the dysfunction of WM microstructure in 22q11DS and its potential importance in elucidating WM abnormalities in psychosis.
| S-EPMC5814141 | biostudies-literature
Project description:A number of studies have shown an abnormal connectivity of certain white matter pathways in developmental dyslexia, as well as correlations between these white matter pathways and behavioral deficits. However, whether developmental dyslexia presents broader white matter network connectivity disruption is currently unknown. The present study reconstructed white matter networks for 26 dyslexic children (11.61 ± 1.31 years) and 31 age-matched controls (11.49 ± 1.36 years) using constrained spherical deconvolution tractography. Network-based statistics (NBS) analysis was performed to identify network connectivity deficits in dyslexic individuals. Network topological features were measured based on graph theory to examine whether these parameters correlate with literacy skills, and whether they explain additional variance over previously established white matter connectivity abnormalities in dyslexic children. The NBS analysis identified a network connecting the left-occipital-temporal cortex and temporo-parietal cortex that had decreased streamlines in dyslexic children. Four network topological parameters (clustering coefficient, local efficiency, transitivity, and global efficiency) were positively correlated with literacy skills of dyslexic children, and explained a substantial proportion of additional variance in literacy skills beyond connectivity measures of white matter pathways. This study for the first time reports a disconnection in a local subnetwork in the left hemisphere in dyslexia and shows that the global white matter network topological properties contribute to reduced literacy skills in dyslexic children.
| S-EPMC6865529 | biostudies-literature
Project description:White matter (WM) plasticity during adulthood is a recently described phenomenon by which experience can shape brain structure. It has been observed in humans using diffusion tensor imaging (DTI) and myelination has been suggested as a possible mechanism. Here, we set out to identify molecular and cellular changes associated with WM plasticity measured by DTI. We combined DTI, immunohistochemistry and mRNA expression analysis and examined the effects of somatosensory experience in adult rats. First, we observed experience-induced DTI differences in WM and in grey matter structure. C-Fos mRNA expression, a marker of cortical activity, in the barrel cortex correlated with the MRI WM metrics, indicating that molecular correlates of cortical activity relate to macroscale measures of WM structure. Analysis of myelin-related genes revealed higher myelin basic protein (MBP) mRNA expression. Higher MBP protein expression was also found via immunohistochemistry in WM. Finally, unbiased RNA sequencing analysis identified 134 differentially expressed genes encoding proteins involved in functions related to cell proliferation and differentiation, regulation of myelination and neuronal activity modulation. In conclusion, macroscale measures of WM plasticity are supported by both molecular and cellular evidence and confirm that myelination is one of the underlying mechanisms.
| S-EPMC7086231 | biostudies-literature