Minocycline improves postoperative cognitive impairment in aged mice by inhibiting astrocytic activation

Abstract

Astrocytes are proving to be critical for the development of cognitive functions. In addition, astrocytic activation contributes toward cognitive impairment induced by chronic cerebral hypoperfusion. Minocycline has been shown to exhibit long-term neuroprotective effects in vascular cognitive impairment rat models through the inhibition of astrogliosis, and has shown potential for the prevention and treatment of postoperative cognitive decline in elderly patients. This study aimed to examine the effect of minocycline on hippocampal astrocytes and long-term postoperative cognitive dysfunction in aged mice. Mice were injected intraperitoneally with 45 mg/kg minocycline once a day for 30 days after 70% hepatectomy. Hippocampal-dependent spatial memory ability was evaluated using the Morris water maze. The expression levels of hippocampal glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule-1 were detected with western blotting, and the hippocampal mRNA relative expression levels of tumor necrosis factor a, interleukin 1 b (IL-1b), and IL-6 were tested using a real-time PCR. The Morris water maze test showed that escape latency and swim distance were prolonged significantly by the surgery, but the extent of impairment was mitigated by minocycline treatment. Hippocampal GFAP and mRNA of tumor necrosis factor a, IL-1b, and IL-6 showed corresponding changes that were consistent with the variations of spatial memory. Minocycline could alleviate hepatectomy-related long-term spatial memory impairment in aged mice, and was associated with reduced levels of hippocampal GFAP and proinflammatory cytokines resulting from astrocytic activation. NeuroReport

Inflammatory insult during pregnancy accelerates age-related behavioral and neurobiochemical changes in CD-1 mice

“…During aging, microglia and astrocytes, the two major cell effectors contribute to chronic activation of neuroinflammation, overexpression of proinflammatory cytokines, and reactive oxygen species. Animal studies show that inhibiting astrocytic activation using antiinflammatory minocycline can alleviate the hepatectomy-related long-term impairment of spatial memory in 19-month-old C57BL/6 mice (Jin et al 2014) and improves cognitive impairment in AD models (Choi et al 2007). Astrocytes become highly reactive in response to neuroinflammation, and the activation of astrocytes is characterized by hypertrophy and cell proliferation, which is associated with GFAP hyper-expression (Eng et al 2000).…”

Surveillance, Phagocytosis, and Inflammation: How Never-Resting Microglia Influence Adult Hippocampal Neurogenesis

“…For instance, both LPS and minocycline affect astrocytic function in vitro and in vivo [65–69]. Furthermore, LPS is known to drive infiltration of monocytes and neutrophils into the brain parenchyma [70].…”

Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes

“…In studies of CIPN, minocycline prevented CIPN-related symptoms and the activation of astrocytes despite the lack of microglial activation indicators [16][17][18][19] . Nevertheless, minocycline also possesses neuroprotective roles [20,28,45,46] . One notable characteristic of minocycline is that it has a direct effect on sodium channels in primary afferent neurons [47] , which suggests it has a role of peripheral analgesia.…”

“…However, accumulating evidence indicates that it prevents chemotherapy-induced peripheral neuropathy (CIPN) via the inhibition of astrocytes [16][17][18][19] . Moreover, it has also been demonstrated that minocycline down-regulates NF-κB activity in several other cell lines [20,21] . Whether minocycline alleviates BCP by inhibiting NF-κB in spinal astrocytes has not been fully explored and understood.…”