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Litter size, age-related memory impairments, and microglial changes in rat dentate gyrus: Stereological analysis and three dimensional morphometry

2013; Elsevier BV; Volume: 238; Linguagem: Inglês

10.1016/j.neuroscience.2013.02.019

1873-7544

Lane Coelho Viana, Camila Mendes de Lima, Marcus Augusto‐Oliveira, Rubilene Pinheiro Borges, Tiago Cardoso, Izabela Almeida, Daniel Guerreiro Diniz, João Bento‐Torres, Antônio Pereira, Manuella Batista‐de‐Oliveira, Allan Lopes, Rosângela Figueiredo Mendes-da-Silva, Ricardo Abadie‐Guedes, Ângela Amâncio dos Santos, Denise Sandrelly Cavalcanti de Lima, Pedro Fernando da Costa Vasconcelos, Colm Cunningham, Rubem Carlos Araújo Guedes, Cristovam Wanderley Picanço Diniz,

Stress Responses and Cortisol

It has been demonstrated that rat litter size affects the immune cell response, but it is not known whether the long-term effects aggravate age-related memory impairments or microglial-associated changes. To that end, we raised sedentary Wistar rats that were first suckled in small or large litters (6 or 12 pups/dam, respectively), then separated into groups of 2–3 rats from the 21st post-natal day to study end. At 4 months (young adult) or 23 months (aged), all individual rats were submitted to spatial memory and object identity recognition tests, and then sacrificed. Brain sections were immunolabeled with anti-IBA-1 antibodies to selectively identify microglia/macrophages. Microglial morphological changes in the molecular layer of the dentate gyrus were estimated based on three-dimensional reconstructions. The cell number and laminar distribution in the dentate gyrus was estimated with the stereological optical fractionator method. We found that, compared to young rat groups, aged rats from large litters showed significant increases in the number of microglia in all layers of the dentate gyrus. Compared to the microglia in all other groups, microglia in aged individuals from large litters showed a significantly higher degree of tree volume expansion, branch base diameter thickening, and cell soma enlargement. These morphological changes were correlated with an increase in the number of microglia in the molecular layer. Young adult individuals from small litters exhibited preserved intact object identity recognition memory and all other groups showed reduced performance in both spatial and object identity recognition tasks. We found that, in large litters, brain development was, on average, associated with permanent changes in the innate immune system in the brain, with a significant impact on the microglial homeostasis of aged rats.