minocycline and Learning-Disabilities

We previously found increased microglial proliferation and pro-inflammatory cytokine release in infant mice compared to juvenile mice after hypoxia-ischemia (HI). The aim of the current study was to assess for differences in the effect of microglial suppression on HI-induced brain injury in infant and juvenile mice. HI was induced in neonatal (P9) and juvenile (P30) mice and minocycline or vehicle was administered at 2h and 24h post-HI. P9 minocycline-treated mice demonstrated early but transient improvements in neurologic injury, while P30 minocycline-treated mice demonstrated sustained improvements in cerebral atrophy and Morris Water Maze performance at 60days post-HI.

Topics: Aging; Animals; Animals, Newborn; Brain; Brain Injuries; CD11b Antigen; Disease Models, Animal; Flow Cytometry; Functional Laterality; Hypoxia-Ischemia, Brain; Learning Disabilities; Leukocyte Common Antigens; Magnetic Resonance Imaging; Maze Learning; Mice; Microglia; Minocycline; Neurologic Examination; Statistics, Nonparametric; Time Factors

Activation of the NF-κB pathway plays an important role in the pathophysiology of Alzheimer's disease (AD), and blocking NF-κB pathway activation has been shown to attenuate cognitive impairment. Diabetic metabolic disorder contributes to β-amyloid protein (Aβ) generation. The goal of this study was to determine the effect of minocycline on Aβ generation and the NF-κB pathway in the hippocampus of diabetic rats and to elucidate the neuroprotective mechanisms of minocycline for the treatment of diabetic metabolic disorder. The diabetic rat model was established using a high-fat diet and an intraperitoneal injection of streptozocin (STZ). Behavioral tests showed that the capacity of learning and memory was significantly lower in diabetic rats. The levels of NF-κB, COX-2, iNOS, IL-1β and TNF-α after the STZ injection were significantly increased in the hippocampus. Significant increases in Aβ, BACE1, NF-κB, COX-2, iNOS, IL-1β and TNF-α were found in diabetic rats. The levels of Aβ, NF-κB, COX-2, iNOS, IL-1β and TNF-α were significantly decreased after minocycline administration; however, minocycline had no effect on BACE1 expression. In sum, diabetes contributes to the activation of the NF-κB pathway and upregulates BACE1 and Aβ. Minocycline downregulates Aβ in the hippocampus by inhibiting NF-κB pathway activation.

Topics: Amyloid beta-Peptides; Animals; Behavior, Animal; Diabetes Mellitus, Experimental; Dietary Fats; Down-Regulation; Hippocampus; Learning Disabilities; Male; Memory Disorders; Minocycline; Neuroprotective Agents; NF-kappa B; Rats; Rats, Wistar; Streptozocin