Minocycline attenuates cholinergic dysfunction and neuro-inflammation-mediatedcognitive impairmentin scopolamine-induced Alzheimer's rat model.

Abstract

Minocycline, a semisynthetictetracycline-derivedantibiotic, has various pharmacological effect such as anti-inflammatory, anti-oxidative stress, and anti-apoptotic effects. The current study investigated the involvement of neuro-inflammatory, oxidative stress, and cholinergic markers in neuroprotection by minocycline against scopolamine-induced brain damage. Minocycline was administered (oral, 10, 15, and 30mg/kg, daily) to groups of amnesic rats for 21days. Passive avoidance memory and spatial learning and memory were assessed. Following that, oxidative stress, cholinergic function, and neuro-inflammation markers were evaluated in the brain tissue. According to our biochemical data, treatment of the scopolamine-injured rats with minocycline decreased the levels of malondialdehyde and acetylcholinesterase (AChE) as well as mRNA expression of AChE and neuro-inflammation markers (tumor necrosis factor-α, interleukin (IL)-1β, IL-6). It also increased the total thiol levels and superoxide dismutase activity as well as mRNA expression of cholinergic receptor M1 (ChRM1). Moreover, minocycline modified distance and latencies in Morris water maze, prolonged latency to enter the black zone and light time while decreasing time spent and frequency of entries to darkness. Taken together, the data indicate that treatment with minocycline improved memory dysfunction mediated possibly through restoring AChE and ChRM1 levels, oxidant/antioxidant balance, as well as inhibiting inflammatory responses.