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AGE-RELATED CHANGES IN COCHLEAR MACROPHAGES AND MICROGLIA AND THEIR IMPACT ON NEURONAL AND BEHAVIORAL OUTCOMES IN CX3CR1+GFP MICE
DEPARTMENT OF ANATOMY AND CELL BIOLOGY, SEOUL NATIONAL UNIVERSITY COLLEGE OF MEDICINE, SEOUL, REPUBLIC OF KOREA
BO-HYEON PARK, DO-EUN KIM, JONG-CHAN JEON, SO-YOUNG KIM
¸ñÀû: This study aimed to investigate age-related changes in macrophages in the cochlea and microglia in the auditory cortex (AC) and hippocampus (HC) in CX3CR1+GFP mice at 7 and 24 months of age. Furthermore, we examined the impact of the depletion of microglia in 24-month-old mice. ¹æ¹ý:The density of macrophages in the cochleae and microglia in the AC and HCs of 7-month-old and 24-month-old CX3CR1+GFP mice were compared. In addition, behavioral tests were conducted for the startle reflex response test and Y-maze test. In four 24-month-old mice, the colony stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 (65 mg/kg) was administered via the drinking water for one month (PLX5622-treated). The density of microglia was estimated by counting GFP-positive ACs and HCs via the QuPath program. Additionally, immunohistochemistry (IHC) of ionized calcium-binding adaptor molecule 1 (Iba1) and transmembrane protein 119 (TMEM119) was performed on the HCs and cochleae. Nissl staining was conducted to assess the neurons in the 7-month-old, 24- month-old, and PLX5622-treated mouse models. °á°ú:Compared with 7-month-old mice, 24-month-old mice presented a greater density of microglia in the AC and HCs. Compared with 7-month-old mice, these mice presented significantly lower prepulse inhibition (PPI) amplitudes and PPI ratios in the startle reflex response test. However, there was no significant difference in movement velocity or spontaneous alternation rate between the two groups in the Y-maze test. Compared with that in 24-month-old control mice, the density of microglia in the HCs and cochleae was lower in PLX5622-treated mice. The level of GFP in the HCs of the PLX5622-treated mice was reduced. However, in the AC, the number of GFP-positive cells was similar between the groups. In the startle reflex test, the PPI ratio was reduced in the PLX5622-treated mice. In the Y maze tests, total arm entry and velocity were reduced in the PLX5622-treated mice. Nissl staining revealed that the number of Nissl-positive neuronal cell bodies was greater with chromatolysis and that the number of Nissl bodies was lower in the PLX5622-treated group than in the 24-month-old control group. °á·Ð:Age-related increases in macrophages in the cochleae and microglia in the AC and HCs were observed in mice. A reduction in the number of microglia resulted in an increase in the PPI ratio and locomotor activity. Additionally, the neurons exhibited chromatolysis with Nissl body depletion, which is indicative of neuronal stress.


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