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Hematopoietic cell activation in the subventricular zone after Theiler's virus infection.

Goings GE, Greisman A, James RE, Abram LK, Begolka WS, Miller SD, Szele FG - J Neuroinflammation (2008)

Bottom Line: In preclinical mice, SVZ neuroblasts emigrated into inflamed periventricular regions.However the number of Dcx+ and polysialylated neural cell adhesion molecule (PSA-NCAM+) SVZ neuroblasts decreased only after periventricular inflammation abated.Our results suggest that after TMEV infection, the SVZ may mount an attempt at neuronal repair via emigration, a process dampened by decreases in neuroblast numbers.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, Anatomy, and Genetics, Oxford University, UK.

ABSTRACT

Background: The periventricular subventricular zone (SVZ) contains stem cells and is an area of active neurogenesis and migration. Since inflammation can reduce neurogenesis, we tested whether Theiler's murine encephalomyelitis virus (TMEV) induces inflammation and reduces neurogenesis in the SVZ.

Methods: We performed immmunohistochemistry for the hematopoietic cell marker CD45 throughout the central nervous system and then examined neuroblasts in the SVZ.

Results: CD45+ activation (inflammation) occurred early in the forebrain and preceded cerebellar and spinal cord inflammation. Inflammation in the brain was regionally stochastic except for the SVZ and surrounding periventricular regions where it was remarkably pronounced and consistent. In preclinical mice, SVZ neuroblasts emigrated into inflamed periventricular regions. The number of proliferating phoshpohistone3+ cells and Doublecortin+ (Dcx) SVZ neuroblasts was overall unaffected during the periods of greatest inflammation. However the number of Dcx+ and polysialylated neural cell adhesion molecule (PSA-NCAM+) SVZ neuroblasts decreased only after periventricular inflammation abated.

Conclusion: Our results suggest that after TMEV infection, the SVZ may mount an attempt at neuronal repair via emigration, a process dampened by decreases in neuroblast numbers.

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CD45 immunohistochemistry shows hematopoietic cell activation in the subventricular zone. A) CD45 expression is barely detectable at low magnifications in control mice. B) Example of CD45 immunohistochemistry in a preclinical mouse. CD45+ cell activation was sporadic throughout the forebrain, but was consistent in the SVZ and septum. svz = subventricular zone, spt = septum. C) Sham mouse showing ramified microglia typical in all control animals. D) Preclinical mouse showing round, activated CD45high microglia. E, F) are early onset and chronic experimental sections. Early onset section shows a mixed population of ramified, intermediate morphology and round microglia. Ramified and intermediate morphologies of microglia predominate in the chronic SVZ. Scale bar C-F = 50 μm. SVZ in C-F outlined based on high density of cells in the SVZ detected with DAPI nuclear staining. G) Higher magnification of ramified microglia in a sham animal. H) Higher magnification from an experimental animal. Scale bar G, H = 20 mm. I, J) CD45 cell activation in the hippocampus is restricted to the CA regions and excluded from the dentate gyrus.
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Figure 5: CD45 immunohistochemistry shows hematopoietic cell activation in the subventricular zone. A) CD45 expression is barely detectable at low magnifications in control mice. B) Example of CD45 immunohistochemistry in a preclinical mouse. CD45+ cell activation was sporadic throughout the forebrain, but was consistent in the SVZ and septum. svz = subventricular zone, spt = septum. C) Sham mouse showing ramified microglia typical in all control animals. D) Preclinical mouse showing round, activated CD45high microglia. E, F) are early onset and chronic experimental sections. Early onset section shows a mixed population of ramified, intermediate morphology and round microglia. Ramified and intermediate morphologies of microglia predominate in the chronic SVZ. Scale bar C-F = 50 μm. SVZ in C-F outlined based on high density of cells in the SVZ detected with DAPI nuclear staining. G) Higher magnification of ramified microglia in a sham animal. H) Higher magnification from an experimental animal. Scale bar G, H = 20 mm. I, J) CD45 cell activation in the hippocampus is restricted to the CA regions and excluded from the dentate gyrus.

Mentions: In examining CD45+ cell activation, we noted that the specific location varied from mouse to mouse, and from section to section. In contrast, CD45+ activation was very consistent in the SVZ and immediately surrounding regions (Figs. 5, 6). Unlike other brain regions that normally exhibit CD45low levels, SVZ cells seem to be constitutively "semi-activated": they have ramified processes and express CD45 at medium (and occasionaly high) levels [7] (Fig. 5C,G). At preclinical TMEV stages, most CD45+ SVZ cells became activated; they were round and CD45high (Fig. 5B,D,H). CD45high cells in and around the SVZ were frequently associated with blood vessels that had perivascular cuffs of activation. SVZ CD45high cells were seen the length of the lateral ventricles, and were prominent in the ventral SVZ (Fig. 2, Fig. 5B, Fig. 6) an area that exhibits a high degree of neurogenesis [36]. Though CD45+ cell activation in the SVZ was present at all time points, the preclinical group had greatest activation and the chronic group the least (Fig. 5D–F, Fig. 6). Interestingly, CD45+ cell activation was also consistently high in the rostral migratory stream as it courses through the anterior cerebral cortex into the olfactory bulb (Fig. 2). Similar to the SVZ, this was characterized by round CD45high cells and was most prominent in preclinical mice.


Hematopoietic cell activation in the subventricular zone after Theiler's virus infection.

Goings GE, Greisman A, James RE, Abram LK, Begolka WS, Miller SD, Szele FG - J Neuroinflammation (2008)

CD45 immunohistochemistry shows hematopoietic cell activation in the subventricular zone. A) CD45 expression is barely detectable at low magnifications in control mice. B) Example of CD45 immunohistochemistry in a preclinical mouse. CD45+ cell activation was sporadic throughout the forebrain, but was consistent in the SVZ and septum. svz = subventricular zone, spt = septum. C) Sham mouse showing ramified microglia typical in all control animals. D) Preclinical mouse showing round, activated CD45high microglia. E, F) are early onset and chronic experimental sections. Early onset section shows a mixed population of ramified, intermediate morphology and round microglia. Ramified and intermediate morphologies of microglia predominate in the chronic SVZ. Scale bar C-F = 50 μm. SVZ in C-F outlined based on high density of cells in the SVZ detected with DAPI nuclear staining. G) Higher magnification of ramified microglia in a sham animal. H) Higher magnification from an experimental animal. Scale bar G, H = 20 mm. I, J) CD45 cell activation in the hippocampus is restricted to the CA regions and excluded from the dentate gyrus.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 5: CD45 immunohistochemistry shows hematopoietic cell activation in the subventricular zone. A) CD45 expression is barely detectable at low magnifications in control mice. B) Example of CD45 immunohistochemistry in a preclinical mouse. CD45+ cell activation was sporadic throughout the forebrain, but was consistent in the SVZ and septum. svz = subventricular zone, spt = septum. C) Sham mouse showing ramified microglia typical in all control animals. D) Preclinical mouse showing round, activated CD45high microglia. E, F) are early onset and chronic experimental sections. Early onset section shows a mixed population of ramified, intermediate morphology and round microglia. Ramified and intermediate morphologies of microglia predominate in the chronic SVZ. Scale bar C-F = 50 μm. SVZ in C-F outlined based on high density of cells in the SVZ detected with DAPI nuclear staining. G) Higher magnification of ramified microglia in a sham animal. H) Higher magnification from an experimental animal. Scale bar G, H = 20 mm. I, J) CD45 cell activation in the hippocampus is restricted to the CA regions and excluded from the dentate gyrus.
Mentions: In examining CD45+ cell activation, we noted that the specific location varied from mouse to mouse, and from section to section. In contrast, CD45+ activation was very consistent in the SVZ and immediately surrounding regions (Figs. 5, 6). Unlike other brain regions that normally exhibit CD45low levels, SVZ cells seem to be constitutively "semi-activated": they have ramified processes and express CD45 at medium (and occasionaly high) levels [7] (Fig. 5C,G). At preclinical TMEV stages, most CD45+ SVZ cells became activated; they were round and CD45high (Fig. 5B,D,H). CD45high cells in and around the SVZ were frequently associated with blood vessels that had perivascular cuffs of activation. SVZ CD45high cells were seen the length of the lateral ventricles, and were prominent in the ventral SVZ (Fig. 2, Fig. 5B, Fig. 6) an area that exhibits a high degree of neurogenesis [36]. Though CD45+ cell activation in the SVZ was present at all time points, the preclinical group had greatest activation and the chronic group the least (Fig. 5D–F, Fig. 6). Interestingly, CD45+ cell activation was also consistently high in the rostral migratory stream as it courses through the anterior cerebral cortex into the olfactory bulb (Fig. 2). Similar to the SVZ, this was characterized by round CD45high cells and was most prominent in preclinical mice.

Bottom Line: In preclinical mice, SVZ neuroblasts emigrated into inflamed periventricular regions.However the number of Dcx+ and polysialylated neural cell adhesion molecule (PSA-NCAM+) SVZ neuroblasts decreased only after periventricular inflammation abated.Our results suggest that after TMEV infection, the SVZ may mount an attempt at neuronal repair via emigration, a process dampened by decreases in neuroblast numbers.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, Anatomy, and Genetics, Oxford University, UK.

ABSTRACT

Background: The periventricular subventricular zone (SVZ) contains stem cells and is an area of active neurogenesis and migration. Since inflammation can reduce neurogenesis, we tested whether Theiler's murine encephalomyelitis virus (TMEV) induces inflammation and reduces neurogenesis in the SVZ.

Methods: We performed immmunohistochemistry for the hematopoietic cell marker CD45 throughout the central nervous system and then examined neuroblasts in the SVZ.

Results: CD45+ activation (inflammation) occurred early in the forebrain and preceded cerebellar and spinal cord inflammation. Inflammation in the brain was regionally stochastic except for the SVZ and surrounding periventricular regions where it was remarkably pronounced and consistent. In preclinical mice, SVZ neuroblasts emigrated into inflamed periventricular regions. The number of proliferating phoshpohistone3+ cells and Doublecortin+ (Dcx) SVZ neuroblasts was overall unaffected during the periods of greatest inflammation. However the number of Dcx+ and polysialylated neural cell adhesion molecule (PSA-NCAM+) SVZ neuroblasts decreased only after periventricular inflammation abated.

Conclusion: Our results suggest that after TMEV infection, the SVZ may mount an attempt at neuronal repair via emigration, a process dampened by decreases in neuroblast numbers.

Show MeSH
Related in: MedlinePlus