Neuroprotective effect of Achillea millefolium aqueous extract against oxidative stress and apoptosis induced by chronic morphine in rat hippocampal CA1 neurons.

Chronic opioid abuse can impair the hippocampal region of the brain. This study evaluates the neuroprotective effect of Achillea millefolium (Ach) on chronic morphine­induced learning and memory impairment, oxidative stress, and neuronal apoptosis in the CA1 region of the rat hippocampus. Thirty­two male Wistar rat rats were classified into four treatment groups (n=8). Morphine sulfate was administered chronically. The treatment groups were given Ach aqueous extract (100, 250, and 500 mg/kg), orally, each day. After 28 days, the Morris water maze test was performed on all subjects. Caspase­3, Bax, and Bcl­2 proteins expression in the CA1 region of hippocampal tissue was analyzed using the western blot method. Also, malondialdehyde concentration, glutathione peroxidase activity, and superoxide dismutase activity were evaluated. The results indicated that Ach extract can improve spatial learning and memory defects in morphine­treated rats. Ach administration also ameliorated apoptosis and oxidative stress indicator levels in hippocampal CA1 of morphine­treated animals. Based on the present study, Ach improved spatial learning and memory defects, and reduced oxidative stress and apoptosis in the hippocampus CA1 region, in chronic morphine­treated animals.

Effect of oleuropein on morphine-induced hippocampus neurotoxicity and memory impairments in rats.

Oleuropein, as an olive leaf extract antioxidant polyphenol, has been reported to be a free radical scavenger. This study was done to investigate the effects of oleuropein, against morphine-induced hippocampus neurotoxicity and memory impairment in rats. The Morris water maze (MWM) test was used to assess the effect of oleuropein (5, 15, and 30 mg/kg, i.p., co-administrated with morphine) on spatial learning and memory of male Wistar rats which were treated with morphine sulfate (45 mg/kg, s.c., 4 weeks). In order to evaluate the cleaved caspase-3, Bax, and Bcl2 protein expression (as biochemical markers of apoptosis) in CA1 area of hippocampus tissue, the western blot test was used. Also, to evaluate the oxidative stress status of hippocampus CA1 area tissue, the malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, and glutathione peroxidase (GPx) activity were assessed. The data showed that oleuropein treatment (15 and 30 mg/kg) improves the spatial learning and memory impairments in morphine-treated animals. Also, oleuropein treatment decreased the apoptosis and oxidative stress levels in the hippocampus CA1 area of morphine-treated rats. Oleuropein can prevent the spatial learning and memory impairments in morphine-treated rats. Molecular mechanisms underlying the observed effects could be at least partially related to the inhibition of neuronal apoptosis and oxidative stress in the hippocampus CA1 area of morphine-treated rats.

CX691, as an AMPA receptor positive modulator, improves the learning and memory in a rat model of Alzheimer's disease.

OBJECTIVES: Growing evidence suggests that dysfunction of the glutamatergic system and α-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) receptors are involved in pathology of Alzheimer's disease (AD). Because AMPA receptors play a key role in plasticity synaptic regulation, positive modulation of these receptors may rescue the cognitive deficits in the AD. The aim of this study was to explore the effect of CX691, a specific positive allosteric modulator of the AMPA-type glutamate receptors (Ampakine), on spatial learning and memory in a rat model of AD. MATERIALS AND METHODS: For induction of AD, amyloid-beta 1-42 (Aß1-42) was microinjected into the hippocampus of male Wistar rats (250-300 g). The Morris water maze (MWM) test was used to evaluate the effect of CX691 (0.03 and 0.3 mg/kg, twice a day for 10 days, orally) on spatial learning and memory of rats. In order to evaluate the protein expression of brain-derived neurotrophic factor (BDNF) in hippocampus tissue, ELISA test was used. RESULTS: The obtained data showed that treatment with CX691 (0.3 mg/kg) improves the impairment of spatial learning and memory in AD rats. Also, treatment with CX691 (0.3 mg/kg), increased the BDNF protein level in hippocampus tissue of AD rats compared to non-treated animals. CONCLUSION: The CX691 can improve the BDNF protein expression as well as spatial performance of learning and memory in AD rats.

Protective effect of atorvastatin on d-galactose-induced aging model in mice.

Atorvastatin (Ator), competitive inhibitors of 3-hydroxymethyl-3-glutaryl-coenzyme-A reductase, is a cholesterol lowering drug. Ator has been shown to have neuroprotective, antioxidant and anti-inflammatory properties making that a potential candidate for the treatment of central nervous system (CNS) disorders. Here we assessed the effect of Ator on the d-galactose (d-gal)-induced aging in mice. For this purpose, Ator (0.1 and 1mg/kg/p.o.), was administrated daily in d-gal-received (500mg/kg/p.o.) mice model of aging for six weeks. Anxiety-like behaviors and cognitive functions were evaluated by the elevated plus-maze and novel object recognition tasks, respectively. Physical power was assessed by forced swimming capacity test. Animals brains were analyzed for the superoxide dismutase (SOD) and brain-derived neurotrophic factor (BDNF). We found that Ator decreases the anxiety-like behaviors in d-gal-treated mice. Also, our behavioral tests showed that Ator reverses the d-gal induced learning and memory impairment. Furthermore, we found that Ator increases the physical power of d-gal-treated mice. Our results indicated that the neuroprotective effect of Ator on d-gal induced neurotoxicity is mediated, at least in part, by an increase in the SOD and BDNF levels. The results of present study suggest that Ator could be used as a novel therapeutic strategy for the treatment of age-related conditions.