Comparison of Ionized Calcium-binding Adapter Molecule 1 Immunoreactivity of the Hippocampal Dentate Gyrus and CA1 Region in Adult and Aged Dogs

Abstract

Similarities between age-related changes in the canine and human brain have resulted in the general acceptance of the canine brain as a model of human brain aging. The hippocampus is essentially required for intact cognitive ability and appears to be particularly vulnerable to the aging process. We observed changes in ionized calcium-binding adapter molecule 1 (Iba-1, a microglial marker) immunoreactivity and protein levels in the hippocampal dentate gyrus and CA1 region of adult (2-3 years) and aged (10-12 years) dogs. We also observed the interferon-gamma (IFN-gamma), a pro-inflammatory cytokine, protein levels in these groups. In the dentate gyrus and CA1 region of the adult dog, Iba-1 immunoreactive microglia were well distributed and their processes were highly ramified. However, in the aged dog, the processes of Iba-1 immunoreactive microglia were hypertrophied in the dentate gyrus. Moreover, Iba-1 protein level in the dentate gyrus in the aged dog was higher than in the adult dog. IFN-gamma expression was increased in the dentate gyrus homogenates of aged dogs than adult dogs. In addition, we found that some neurons were positive to Fluoro-Jade B (a marker for neuronal degeneration) in the dentate polymorphic layer, but not in the hippocampal CA1 region in the aged dog. These results suggest that Iba-1 immunoreactive microglia are hypertrophied in the dentate gyrus in the aged dog.

Comparison of Ionized Calcium-binding Adapter Molecule 1-Immunoreactive Microglia in the Spinal Cord Between Young Adult and Aged Dogs

“…In addition, IFN-c protein levels were significantly increased in the spinal cord in the aged dogs compared to those in the adult dogs. This result is supported by previous studies that the expression of IFN-c was increased in the frontal portion of the SAMP10 brain [29] and increased in the dentate gyrus of aged dogs [25]. It has been reported that low concentrations of IFN-c modulate the adaptive immune response by directing microglia to differentiate to antigen presenting cells [30].…”

“…In addition, Iba-1 protein levels were increased in the aged group. Indeed, many studies of age-related cellular, especially microglial, changes in the CNS have been performed [24][25][26][27]. Among the microglia classifications, ramified microglia are known as resting microglia.…”

Cognitive and Behavioral Consequences of Impaired Immunoregulation in Aging

“…These neuroinflammatory processes are normally transient, with microglia returning to a resting state as the immune stimulus is resolved. Microglia from the brain of aged gerbils (Choi et al 2007)and dogs (Hwang et al 2008) show a shift towards a more activated morphology (thickened and deramified processes) compared to young adults as determined by Iba1 staining. These morphological changes correspond with an increase in the expression of inflammatory markers in the brain of normal aged rats (Perry et al 1993), primates (Sheffield and Berman 1998), and humans (Streit and Sparks 1997;Kaunzner et al 2010).…”

Neurotrophin‐3 released from implant of tissue‐engineered fibroin scaffolds inhibits inflammation, enhances nerve fiber regeneration, and improves motor function in canine spinal cord injury

“…Therefore, immune reaction assessment is crucial for effective treatment for SCI. Typically, IBA‐1 cells have prominent and ramified processes, indicating that some of them are microglia derived 29, 30. To investigate the inflammatory response, IBA‐1 immunohistochemistry was carried out following NF‐GS graft.…”