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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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Microglial sex differences in the developing cerebellum. A–D, Estimated density of microglia based on morphology in the GL at P17. Males had more microglia with thin processes than females (*p = 0.026). No significant differences were found for sex in round/amoeboid microglia, stout microglia (p = 0.270) or microglia with thick processes (p = 0.127). E–H, Estimated density of microglia based on morphology in the ML at P17. The statistical analysis indicated no sex differences in round/amoeboid (p = 0.375), stout (p = 0.646), microglia with thick processes (p = 0.168), or microglia with thin processes (p = 0.137). Data are expressed as mean ± SEM (n = 6, 3 males + 3 females for each group).
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Figure 7: Microglial sex differences in the developing cerebellum. A–D, Estimated density of microglia based on morphology in the GL at P17. Males had more microglia with thin processes than females (*p = 0.026). No significant differences were found for sex in round/amoeboid microglia, stout microglia (p = 0.270) or microglia with thick processes (p = 0.127). E–H, Estimated density of microglia based on morphology in the ML at P17. The statistical analysis indicated no sex differences in round/amoeboid (p = 0.375), stout (p = 0.646), microglia with thick processes (p = 0.168), or microglia with thin processes (p = 0.137). Data are expressed as mean ± SEM (n = 6, 3 males + 3 females for each group).

Mentions: We looked at sex differences in the cerebellum in terms of microglia density at P17 in both the GL and ML to determine whether at this unique time point the cerebellum develops differently according to sex. We found that males have a higher density of microglia with thin processes than females in the GL (p = 0.026t; Fig. 7D). No significant differences were found in any other of the morphological categorization of microglia in the GL (round/amoeboid; t(4) = 0.000q; stout, p = 0.270r; with thick processes, p = 0.127s; Fig. 7A–C) or the ML (round/amoeboid, p = 0.375u; stout, p = 0.646v; with thick processes, p = 0.168w; with thin processes, p = 0.137x; Fig. 7E–H). Also, there were no significant differences between males and females for phagocytic cups in the GL (p = 0.356)y or ML (p = 0.159)z. The same results were found for total microglia (GL, p = 0.423aa; ML, p = 0.256bb).


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

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

Microglial sex differences in the developing cerebellum. A–D, Estimated density of microglia based on morphology in the GL at P17. Males had more microglia with thin processes than females (*p = 0.026). No significant differences were found for sex in round/amoeboid microglia, stout microglia (p = 0.270) or microglia with thick processes (p = 0.127). E–H, Estimated density of microglia based on morphology in the ML at P17. The statistical analysis indicated no sex differences in round/amoeboid (p = 0.375), stout (p = 0.646), microglia with thick processes (p = 0.168), or microglia with thin processes (p = 0.137). Data are expressed as mean ± SEM (n = 6, 3 males + 3 females for each group).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4596010&req=5

Figure 7: Microglial sex differences in the developing cerebellum. A–D, Estimated density of microglia based on morphology in the GL at P17. Males had more microglia with thin processes than females (*p = 0.026). No significant differences were found for sex in round/amoeboid microglia, stout microglia (p = 0.270) or microglia with thick processes (p = 0.127). E–H, Estimated density of microglia based on morphology in the ML at P17. The statistical analysis indicated no sex differences in round/amoeboid (p = 0.375), stout (p = 0.646), microglia with thick processes (p = 0.168), or microglia with thin processes (p = 0.137). Data are expressed as mean ± SEM (n = 6, 3 males + 3 females for each group).
Mentions: We looked at sex differences in the cerebellum in terms of microglia density at P17 in both the GL and ML to determine whether at this unique time point the cerebellum develops differently according to sex. We found that males have a higher density of microglia with thin processes than females in the GL (p = 0.026t; Fig. 7D). No significant differences were found in any other of the morphological categorization of microglia in the GL (round/amoeboid; t(4) = 0.000q; stout, p = 0.270r; with thick processes, p = 0.127s; Fig. 7A–C) or the ML (round/amoeboid, p = 0.375u; stout, p = 0.646v; with thick processes, p = 0.168w; with thin processes, p = 0.137x; Fig. 7E–H). Also, there were no significant differences between males and females for phagocytic cups in the GL (p = 0.356)y or ML (p = 0.159)z. The same results were found for total microglia (GL, p = 0.423aa; ML, p = 0.256bb).

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