Mitochondrial involvement in memory impairment induced by scopolamine in rats
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Published on: July 8, 2015
Maylin Wong-Guerra1, Javier Jiménez-Martin2, Gilberto L Pardo-Andreu3
1a Laboratorio de Neuroprotección , Centro de Investigación y Desarrollo de Medicamentos , La Habana , Cuba.
Objective:
Scopolamine (SCO) administration to rats induces molecular features of AD and other dementias, including impaired cognition, increased oxidative stress, and imbalanced cholinergic transmission. Although mitochondrial dysfunction is involved in different types of dementias, its role in cognitive impairment induced by SCO has not been well elucidated. The aim of this work was to evaluate the in vivo effect of SCO on different brain mitochondrial parameters in rats to explore its neurotoxic mechanisms of action.
Methods:
Saline (Control) or SCO (1 mg/kg) was administered intraperitoneally 30 min prior to neurobehavioral and biochemical evaluations. Novel object recognition and Y-maze paradigms were used to evaluate the impact on memory, while redox profiles in different brain regions and the acetylcholinesterase (AChE) activity of the whole brain were assessed to elucidate the amnesic mechanism of SCO. Finally, the effects of SCO on brain mitochondria were evaluated both ex vivo and in vitro, the latter to determine whether SCO could directly interfere with mitochondrial function.
Results:
SCO administration induced memory deficit, increased oxidative stress, and increased AChE activities in the hippocampus and prefrontal cortex. Isolated brain mitochondria from rats administered with SCO were more vulnerable to mitochondrial swelling, membrane potential dissipation, H2O2 generation and calcium efflux, all likely resulting from oxidative damage. The in vitro mitochondrial assays suggest that SCO did not affect the organelle function directly.
Conclusion:
In conclusion, the present results indicate that SCO induced cognitive dysfunction and oxidative stress may involve brain mitochondrial impairment, an important target for new neuroprotective compounds against AD and other dementias.
Insights
Scopolamine (SCO) impairs rat cognition and brain function by damaging mitochondria, highlighting a potential target for dementia therapies. This study reveals SCO-induced mitochondrial dysfunction contributes to cognitive deficits and oxidative stress.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Scopolamine (SCO) administration in rats mimics Alzheimer's disease (AD) features, including cognitive deficits and oxidative stress.
- Mitochondrial dysfunction is implicated in various dementias, but its role in SCO-induced cognitive impairment requires further investigation.
Purpose of the Study:
- To investigate the in vivo effects of SCO on rat brain mitochondrial parameters.
- To elucidate the neurotoxic mechanisms underlying SCO-induced cognitive impairment.
Main Methods:
- Rats received saline (control) or SCO (1 mg/kg) followed by neurobehavioral tests (novel object recognition, Y-maze) and biochemical analyses.
- Redox profiles, acetylcholinesterase (AChE) activity, and brain mitochondrial function (ex vivo and in vitro) were assessed.
Main Results:
- SCO administration resulted in memory deficits, increased oxidative stress, and elevated AChE activity in the hippocampus and prefrontal cortex.
- Isolated brain mitochondria from SCO-treated rats exhibited increased vulnerability to swelling, membrane potential dissipation, H2O2 generation, and calcium efflux.
- In vitro assays indicated SCO does not directly impair mitochondrial function.
Conclusions:
- SCO-induced cognitive dysfunction and oxidative stress appear to involve impairment of brain mitochondria.
- Mitochondrial impairment represents a significant therapeutic target for developing neuroprotective agents against AD and other dementias.
