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Published on: March 23, 2011
Minocycline enhances hippocampal memory, neuroplasticity and synapse-associated proteins in aged C57 BL/6 mice
Ying Jiang1, Yingying Liu1, Cansheng Zhu1
1Department of Neurology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, Guangdong 510630, China.
Abstract:
Previous studies have suggested that minocycline can attenuate cognitive deficits in animal models of conditions such as Alzheimer's disease and cerebral ischemia through inhibiting microglia associated anti-inflammatory actions. However the pathway that minocycline targets to enhance cognitive performance is not fully defined. Here we examined the effects of minocycline on learning and memory in aged (22-month-old) C57 BL/6 mice. We treated one group of mice with minocycline (30 mg/kg/day), and another group of mice with donepezil (2 mg/kg/day) as a positive control. The Morris water maze and passive avoidance tests were used to evaluate the effects of minocycline on learning and memory deficits. We also used high-frequency stimulation-induced long-term potentiation and Golgi-Cox staining to assess the effect of minocycline on synaptic plasticity and synaptogenesis. The effects of minocycline on synapse-associated signaling proteins were determined by western blot. We found that minocycline ameliorates cognitive deficits, enhances neuroplasticity, activates brain-derived neurotrophic factor- extracellular signal-regulated kinases signaling and increases expression of Arc, EGR1 and PSD-95 in the CA1 and dentate gyrus regions of the hippocampus in aged mice. The effects of minocycline in aged mice were similar to those of donepezil. Our results suggest that minocycline could improve learning and memory through enhancing synaptic plasticity and synaptogenesis, modulating the expression of synapse-associated signaling proteins, which provide a rationale for exploring the viability of using minocycline treatment in cognitive deficits.
Insights
Minocycline improves learning and memory in aged mice by enhancing synaptic plasticity and activating key signaling pathways. These effects are comparable to donepezil, suggesting potential for cognitive deficit treatment.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Minocycline's anti-inflammatory actions are known to attenuate cognitive deficits in animal models.
- The precise pathways targeted by minocycline to improve cognition remain incompletely understood.
Purpose of the Study:
- To investigate the effects of minocycline on learning and memory in aged mice.
- To elucidate the molecular mechanisms underlying minocycline's cognitive-enhancing effects.
Main Methods:
- Aged C57 BL/6 mice were treated with minocycline or donepezil (positive control).
- Cognitive function was assessed using the Morris water maze and passive avoidance tests.
- Synaptic plasticity, synaptogenesis, and associated signaling proteins were evaluated using electrophysiology, Golgi-Cox staining, and western blot.
Main Results:
- Minocycline ameliorated cognitive deficits in aged mice.
- The treatment enhanced neuroplasticity and activated the brain-derived neurotrophic factor-extracellular signal-regulated kinases signaling pathway.
- Expression of Arc, EGR1, and PSD-95 in the hippocampus was increased by minocycline, similar to donepezil.
Conclusions:
- Minocycline improves learning and memory in aged mice by enhancing synaptic plasticity and synaptogenesis.
- Modulation of synapse-associated signaling proteins is a key mechanism.
- These findings support exploring minocycline for treating cognitive deficits.
