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Morphological and Phagocytic Profile of Microglia in the Developing Rat Cerebellum(1,2,3).

Perez-Pouchoulen M, VanRyzin JW, McCarthy MM - eNeuro (2015)

Bottom Line: We found that microglial morphology changed from amoeboid to ramified during the first 3 postnatal weeks in a region specific manner.At P17 males showed an approximately twofold increase in microglia with thin processes compared with females.Our findings indicate a continuous process of microglial maturation and a nonuniform distribution of microglia in the cerebellar cortex that implicates microglia as an important cellular component of the developing cerebellum.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacology, University of Maryland School of Medicine , Baltimore, Maryland 21201.

ABSTRACT
Microglia are being increasingly recognized as playing important roles in neurodevelopment. The cerebellum matures postnatally, undergoing major growth, but the role of microglia in the developing cerebellum is not well understood. Using the laboratory rat we quantified and morphologically categorized microglia throughout the vermis and across development using a design-based unbiased stereology method. We found that microglial morphology changed from amoeboid to ramified during the first 3 postnatal weeks in a region specific manner. These morphological changes were accompanied by the sudden appearance of phagocytic cups during the third postnatal week from P17 to P19, with an approximately fourfold increase compared with the first week, followed by a prompt decline at the end of the third week. The microglial phagocytic cups were significantly higher in the granular layer (∼69%) than in the molecular layer (ML; ∼31%) during a 3 d window, and present on ∼67% of microglia with thick processes and ∼33% of microglia with thin processes. Similar proportions of phagocytic cups associated to microglia with either thick or thin processes were found in the ML. We observed cell nuclei fragmentation and cleaved caspase-3 expression within some microglial phagocytic cups, presumably from dying granule neurons. At P17 males showed an approximately twofold increase in microglia with thin processes compared with females. Our findings indicate a continuous process of microglial maturation and a nonuniform distribution of microglia in the cerebellar cortex that implicates microglia as an important cellular component of the developing cerebellum.

No MeSH data available.


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Microglia location in the cerebellar cortex based on morphological classification. A, Total microglia were significantly higher in the GL than the ML during the second and third postnatal week in the cerebellum (*p < 0.05, **p < 0.01, ***p < 0.000). B, The density of round/amoeboid microglia was very low and did not differ between the ML and the GL from P12 to P21. C, The density of stout microglia was significantly higher in the ML than the GL at all days examined except P14 (**p < 0.01, ***p < 0.000). D, Microglia with thick processes were the most abundant but did not differ between the ML and the GL. E, There were significantly more microglia with thin processes in the GL than the ML at P17 and P21 but not at younger ages examined (*p < 0.05, ***p < 0.000). All data are expressed as mean ± SEM (n = 6, 3 males + 3 females for each group).
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Figure 4: Microglia location in the cerebellar cortex based on morphological classification. A, Total microglia were significantly higher in the GL than the ML during the second and third postnatal week in the cerebellum (*p < 0.05, **p < 0.01, ***p < 0.000). B, The density of round/amoeboid microglia was very low and did not differ between the ML and the GL from P12 to P21. C, The density of stout microglia was significantly higher in the ML than the GL at all days examined except P14 (**p < 0.01, ***p < 0.000). D, Microglia with thick processes were the most abundant but did not differ between the ML and the GL. E, There were significantly more microglia with thin processes in the GL than the ML at P17 and P21 but not at younger ages examined (*p < 0.05, ***p < 0.000). All data are expressed as mean ± SEM (n = 6, 3 males + 3 females for each group).

Mentions: To test whether the density of total microglia and/or their morphology differs based on anatomical location in the cerebellar cortex, we counted microglia separately in both the GL and ML at different time points during postnatal development. A significant interaction for age X cerebellar layer was found for total microglia (p < 0.000)g. The GL layer had a higher density of total microglia compared with the ML at P12 (p = 0.007), P14 (p = 0.025), P17 (p = 0.010), and P21 (p < 0.000; Fig. 4A). When we looked at the microglial morphology, there was a significant interaction of age X cerebellar layer for stout microglia (p = 0.05)i. The ML exhibited a higher density of stout microglia than GL at P12 (p < 0.000), P17 (p = 0.007) and P21 (p < 0.000), but not at P14 (p = 0.261) (Fig. 4C). Likewise, a significant interaction for age X cerebellar layer was detected for microglia with thin processes (p < 0.000)k. We found the GL to have higher density of microglia with thin processes than the ML later in development (P17; p = 0.05, P21; p < 0.000), but not earlier (P12; p = 0.56, P14; p = 0.91; Fig. 4E). No significant interactions for age X cerebellar layer were found for round/amoeboid microglia (p = 0.74; Fig. 4B)h or for microglia with thick processes (p = 0.88; Fig. 4D)j.


Morphological and Phagocytic Profile of Microglia in the Developing Rat Cerebellum(1,2,3).

Perez-Pouchoulen M, VanRyzin JW, McCarthy MM - eNeuro (2015)

Microglia location in the cerebellar cortex based on morphological classification. A, Total microglia were significantly higher in the GL than the ML during the second and third postnatal week in the cerebellum (*p < 0.05, **p < 0.01, ***p < 0.000). B, The density of round/amoeboid microglia was very low and did not differ between the ML and the GL from P12 to P21. C, The density of stout microglia was significantly higher in the ML than the GL at all days examined except P14 (**p < 0.01, ***p < 0.000). D, Microglia with thick processes were the most abundant but did not differ between the ML and the GL. E, There were significantly more microglia with thin processes in the GL than the ML at P17 and P21 but not at younger ages examined (*p < 0.05, ***p < 0.000). All data are expressed as mean ± SEM (n = 6, 3 males + 3 females for each group).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 4: Microglia location in the cerebellar cortex based on morphological classification. A, Total microglia were significantly higher in the GL than the ML during the second and third postnatal week in the cerebellum (*p < 0.05, **p < 0.01, ***p < 0.000). B, The density of round/amoeboid microglia was very low and did not differ between the ML and the GL from P12 to P21. C, The density of stout microglia was significantly higher in the ML than the GL at all days examined except P14 (**p < 0.01, ***p < 0.000). D, Microglia with thick processes were the most abundant but did not differ between the ML and the GL. E, There were significantly more microglia with thin processes in the GL than the ML at P17 and P21 but not at younger ages examined (*p < 0.05, ***p < 0.000). All data are expressed as mean ± SEM (n = 6, 3 males + 3 females for each group).
Mentions: To test whether the density of total microglia and/or their morphology differs based on anatomical location in the cerebellar cortex, we counted microglia separately in both the GL and ML at different time points during postnatal development. A significant interaction for age X cerebellar layer was found for total microglia (p < 0.000)g. The GL layer had a higher density of total microglia compared with the ML at P12 (p = 0.007), P14 (p = 0.025), P17 (p = 0.010), and P21 (p < 0.000; Fig. 4A). When we looked at the microglial morphology, there was a significant interaction of age X cerebellar layer for stout microglia (p = 0.05)i. The ML exhibited a higher density of stout microglia than GL at P12 (p < 0.000), P17 (p = 0.007) and P21 (p < 0.000), but not at P14 (p = 0.261) (Fig. 4C). Likewise, a significant interaction for age X cerebellar layer was detected for microglia with thin processes (p < 0.000)k. We found the GL to have higher density of microglia with thin processes than the ML later in development (P17; p = 0.05, P21; p < 0.000), but not earlier (P12; p = 0.56, P14; p = 0.91; Fig. 4E). No significant interactions for age X cerebellar layer were found for round/amoeboid microglia (p = 0.74; Fig. 4B)h or for microglia with thick processes (p = 0.88; Fig. 4D)j.

Bottom Line: We found that microglial morphology changed from amoeboid to ramified during the first 3 postnatal weeks in a region specific manner.At P17 males showed an approximately twofold increase in microglia with thin processes compared with females.Our findings indicate a continuous process of microglial maturation and a nonuniform distribution of microglia in the cerebellar cortex that implicates microglia as an important cellular component of the developing cerebellum.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacology, University of Maryland School of Medicine , Baltimore, Maryland 21201.

ABSTRACT
Microglia are being increasingly recognized as playing important roles in neurodevelopment. The cerebellum matures postnatally, undergoing major growth, but the role of microglia in the developing cerebellum is not well understood. Using the laboratory rat we quantified and morphologically categorized microglia throughout the vermis and across development using a design-based unbiased stereology method. We found that microglial morphology changed from amoeboid to ramified during the first 3 postnatal weeks in a region specific manner. These morphological changes were accompanied by the sudden appearance of phagocytic cups during the third postnatal week from P17 to P19, with an approximately fourfold increase compared with the first week, followed by a prompt decline at the end of the third week. The microglial phagocytic cups were significantly higher in the granular layer (∼69%) than in the molecular layer (ML; ∼31%) during a 3 d window, and present on ∼67% of microglia with thick processes and ∼33% of microglia with thin processes. Similar proportions of phagocytic cups associated to microglia with either thick or thin processes were found in the ML. We observed cell nuclei fragmentation and cleaved caspase-3 expression within some microglial phagocytic cups, presumably from dying granule neurons. At P17 males showed an approximately twofold increase in microglia with thin processes compared with females. Our findings indicate a continuous process of microglial maturation and a nonuniform distribution of microglia in the cerebellar cortex that implicates microglia as an important cellular component of the developing cerebellum.

No MeSH data available.


Related in: MedlinePlus