Age-Induced Spatial Memory Deficits in Rats Are Correlated with Specific Brain Region Alterations in Microglial Morphology and Gene Expression

Shai Shoham; Michal Linial; Marta Weinstock

doi:10.1007/s11481-018-9817-2

Age-Induced Spatial Memory Deficits in Rats Are Correlated with Specific Brain Region Alterations in Microglial Morphology and Gene Expression

Shai Shoham, Michal Linial, Marta Weinstock^*

^*Corresponding author for this work

Department of Biological Chemistry

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

Effect of age and ladostigil treatment (1 mg/kg/day), given for 6 months to 16 month old rats, was investigated on microglial morphology in brain regions associated with control of spatial learning. This was assessed in the Morris water maze (MWM). Microglial morphology was assessed with diaminobenzidine and fluorescent staining with Iba1 and CD11b in these brain regions. Aging did not change the number of microglia in the parietal cortex (PC) or hippocampal CA1 region (CA1-HC), but decreased microglial process tips in the CA1-HC, increased the area fraction stained by CD11b and number of bulbs on processes in PC and CA1-HC and thickness of microglial processes in corpus callosum (CC) and fornix (Fx). Performance in MWM (distance swam to escape platform) was negatively correlated with number of bulbs in PC and thickness of process in CC, and positively correlated with number of process tips in CA1-HC. Aging increased expression of MHC class II genes and others associated with motility and membrane adhesion in the PC and hippocampus, but Adora2a (Adenosine A2a receptor), only in hippocampus. Age-related increase in the number of bulbs and expression of inflammatory genes was prevented by ladostigil in PC. In the CA1-HC, ladostigil increased the number of process tips and prevented the increase in expression of Adora2a and genes regulating ion channels. Ladostigil also decreased thickening of the processes in CC and Fx. The data show brain region-specific relations induced by age in spatial learning, microglial morphology and associated genes and their response to ladostigil treatment. [Figure not available: see fulltext.].

Original language	American English
Pages (from-to)	251-262
Number of pages	12
Journal	Journal of NeuroImmune Pharmacology
Volume	14
Issue number	2
DOIs	https://doi.org/10.1007/s11481-018-9817-2
State	Published - 15 Jun 2019

Bibliographical note

Funding Information:
Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors, but was supported by research funds of MW at the Hebrew University.

Publisher Copyright:
© 2018, Springer Science+Business Media, LLC, part of Springer Nature.

Keywords

Hippocampus
KEGG pathway
Microglial morphology
Parietal cortex
RNA-Seq

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10.1007/s11481-018-9817-2

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title = "Age-Induced Spatial Memory Deficits in Rats Are Correlated with Specific Brain Region Alterations in Microglial Morphology and Gene Expression",

abstract = "Effect of age and ladostigil treatment (1 mg/kg/day), given for 6 months to 16 month old rats, was investigated on microglial morphology in brain regions associated with control of spatial learning. This was assessed in the Morris water maze (MWM). Microglial morphology was assessed with diaminobenzidine and fluorescent staining with Iba1 and CD11b in these brain regions. Aging did not change the number of microglia in the parietal cortex (PC) or hippocampal CA1 region (CA1-HC), but decreased microglial process tips in the CA1-HC, increased the area fraction stained by CD11b and number of bulbs on processes in PC and CA1-HC and thickness of microglial processes in corpus callosum (CC) and fornix (Fx). Performance in MWM (distance swam to escape platform) was negatively correlated with number of bulbs in PC and thickness of process in CC, and positively correlated with number of process tips in CA1-HC. Aging increased expression of MHC class II genes and others associated with motility and membrane adhesion in the PC and hippocampus, but Adora2a (Adenosine A2a receptor), only in hippocampus. Age-related increase in the number of bulbs and expression of inflammatory genes was prevented by ladostigil in PC. In the CA1-HC, ladostigil increased the number of process tips and prevented the increase in expression of Adora2a and genes regulating ion channels. Ladostigil also decreased thickening of the processes in CC and Fx. The data show brain region-specific relations induced by age in spatial learning, microglial morphology and associated genes and their response to ladostigil treatment. [Figure not available: see fulltext.].",

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note = "Funding Information: Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors, but was supported by research funds of MW at the Hebrew University. Publisher Copyright: {\textcopyright} 2018, Springer Science+Business Media, LLC, part of Springer Nature.",

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AU - Shoham, Shai

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AU - Weinstock, Marta

N1 - Funding Information: Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors, but was supported by research funds of MW at the Hebrew University. Publisher Copyright: © 2018, Springer Science+Business Media, LLC, part of Springer Nature.

PY - 2019/6/15

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N2 - Effect of age and ladostigil treatment (1 mg/kg/day), given for 6 months to 16 month old rats, was investigated on microglial morphology in brain regions associated with control of spatial learning. This was assessed in the Morris water maze (MWM). Microglial morphology was assessed with diaminobenzidine and fluorescent staining with Iba1 and CD11b in these brain regions. Aging did not change the number of microglia in the parietal cortex (PC) or hippocampal CA1 region (CA1-HC), but decreased microglial process tips in the CA1-HC, increased the area fraction stained by CD11b and number of bulbs on processes in PC and CA1-HC and thickness of microglial processes in corpus callosum (CC) and fornix (Fx). Performance in MWM (distance swam to escape platform) was negatively correlated with number of bulbs in PC and thickness of process in CC, and positively correlated with number of process tips in CA1-HC. Aging increased expression of MHC class II genes and others associated with motility and membrane adhesion in the PC and hippocampus, but Adora2a (Adenosine A2a receptor), only in hippocampus. Age-related increase in the number of bulbs and expression of inflammatory genes was prevented by ladostigil in PC. In the CA1-HC, ladostigil increased the number of process tips and prevented the increase in expression of Adora2a and genes regulating ion channels. Ladostigil also decreased thickening of the processes in CC and Fx. The data show brain region-specific relations induced by age in spatial learning, microglial morphology and associated genes and their response to ladostigil treatment. [Figure not available: see fulltext.].

AB - Effect of age and ladostigil treatment (1 mg/kg/day), given for 6 months to 16 month old rats, was investigated on microglial morphology in brain regions associated with control of spatial learning. This was assessed in the Morris water maze (MWM). Microglial morphology was assessed with diaminobenzidine and fluorescent staining with Iba1 and CD11b in these brain regions. Aging did not change the number of microglia in the parietal cortex (PC) or hippocampal CA1 region (CA1-HC), but decreased microglial process tips in the CA1-HC, increased the area fraction stained by CD11b and number of bulbs on processes in PC and CA1-HC and thickness of microglial processes in corpus callosum (CC) and fornix (Fx). Performance in MWM (distance swam to escape platform) was negatively correlated with number of bulbs in PC and thickness of process in CC, and positively correlated with number of process tips in CA1-HC. Aging increased expression of MHC class II genes and others associated with motility and membrane adhesion in the PC and hippocampus, but Adora2a (Adenosine A2a receptor), only in hippocampus. Age-related increase in the number of bulbs and expression of inflammatory genes was prevented by ladostigil in PC. In the CA1-HC, ladostigil increased the number of process tips and prevented the increase in expression of Adora2a and genes regulating ion channels. Ladostigil also decreased thickening of the processes in CC and Fx. The data show brain region-specific relations induced by age in spatial learning, microglial morphology and associated genes and their response to ladostigil treatment. [Figure not available: see fulltext.].

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SN - 1557-1890

VL - 14

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EP - 262

JO - Journal of NeuroImmune Pharmacology

JF - Journal of NeuroImmune Pharmacology

IS - 2

ER -

Age-Induced Spatial Memory Deficits in Rats Are Correlated with Specific Brain Region Alterations in Microglial Morphology and Gene Expression

Abstract

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Keywords

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