PURPOSE: Alzheimer's disease (AD) results in memory impairment and neuronal cell death in the brain. Previous studies demonstrated that intracerebroventricular administration of streptozotocin (STZ) induces pathological and behavioral alterations similar to those observed in AD. Agmatine (Agm) has been shown to exert neuroprotective effects in central nervous system disorders. In this study, we investigated whether Agm treatment could attenuate apoptosis and improve cognitive decline in a STZ-induced Alzheimer rat model. MATERIALS AND METHODS: We studied the effect of Agm on AD pathology using a STZ-induced Alzheimer rat model. For each experiment, rats were given anesthesia (chloral hydrate 300 mg/kg, ip), followed by a single injection of STZ (1.5 mg/kg) bilaterally into each lateral ventricle (5 microL/ventricle). Rats were injected with Agm (100 mg/kg) daily up to two weeks from the surgery day. RESULTS: Agm suppressed the accumulation of amyloid beta and enhanced insulin signal transduction in STZ-induced Alzheimer rats [experimetal control (EC) group]. Upon evaluation of cognitive function by Morris water maze testing, significant improvement of learning and memory dysfunction in the STZ-Agm group was observed compared with the EC group. Western blot results revealed significant attenuation of the protein expressions of cleaved caspase-3 and Bax, as well as increases in the protein expressions of Bcl2, PI3K, Nrf2, and gamma-glutamyl cysteine synthetase, in the STZ-Agm group. CONCLUSION: Our results showed that Agm is involved in the activation of antioxidant signaling pathways and activation of insulin signal transduction. Accordingly, Agm may be a promising therapeutic agent for improving cognitive decline and attenuating apoptosis in AD.
Agmatine/*therapeutic use ; Alzheimer Disease/*chemically induced/*drug therapy ; Animals ; Cognition Disorders/*chemically induced/*drug therapy ; Disease Models, Animal ; Male ; Rats ; Streptozocin/*toxicity

BACKGROUNDThe advent of brain stimulation techniques to treat movement disorders and psychiatric diseases has shown potential to decode the neural mechanism that underlies the cognitive process by modulating the interrupted circuit. Here, the present investigation aimed at evaluating the influence of deep brain stimulation of the anterior nucleus thalamus (ANT-DBS) on memory.

METHODSThirty-two rats were randomized into phosphate buffer saline (PBS) group (n = 8, rats received PBS injections without implantation of electrodes into the ANT), Alzheimer's dementia (AD) group (n = 8, rats received Aβ1-40 injections without implantation of electrodes into the ANT), ANT sham stimulation group (n = 8, rats received Aβ1-40 injections with implantation of electrodes into the ANT but without stimulation) and ANT stimulation group (n = 8, rats received Aβ1-40 injections with implantation of electrodes into the ANT and stimulation). A Morris maze test was used for determining the effect of electrical stimulation on cognitive function in rats. The data were assessed statistically with one-way analysis of variance (ANOVA) followed by Tukey's tests for multiple post hoc comparisons.

RESULTSThe data showed that in the training test, PBS group and AD group managed to learn the hidden-platform faster and faster while AD group needed a significantly longer time to reach the platform than PBS group (P < 0.05). Meanwhile, ANT stimulation group demonstrated a significantly shorter time to reach the platform (P < 0.05) compared to the AD group, while there was no significant difference between the ANT sham stimulation group and the AD group (P > 0.05). On the probe test, the AD group spent less time ((10.15 ± 2.34) seconds) in the target quadrant than the PBS group ((28.20 ± 2.75) seconds) (P < 0.05). And the times of platform-traversing of the AD group (3.35 ± 1.12) significantly decreased compared with the PBS group (8.69 ± 2.87) (P < 0.05). However, the times of platform-traversing and the time spent in the target quadrant of the ANT stimulation group significantly increased compared to the AD group (P < 0.05), while times of platform-traversing or the time spent in the target quadrant was not significantly different between the ANT sham stimulation group and the AD group (P > 0.05).

CONCLUSIONBilateral high-frequency stimulation of the ANT may be useful as a potential therapeutic modality for cognitive dysfunction in AD.

Amyloid beta-Peptides ; administration & dosage ; toxicity ; Animals ; Anterior Thalamic Nuclei ; drug effects ; Cognition ; drug effects ; Cognition Disorders ; chemically induced ; therapy ; Deep Brain Stimulation ; methods ; Hippocampus ; drug effects ; Male ; Peptide Fragments ; administration & dosage ; toxicity ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the influence of repeated seizures and anti-epileptic drug on phosphorylated cAMP response element binding protein (pCREB) in rat model of cognitive impairment, and the effect of Caoguo Zhimu Decoction (CZD) on it.

METHODSOn the basis of epileptic model induced by pentylenetetrazol (PTZ), cognitive impairment model was induced by kindling epilepsy with PTZ everyday, which were then di-vided into the model-1 group, the CZD-1 group, the nimodipine-1 group, and those by injecting large dosage phenytoin sodium were divided into the model-2 group, the CZD-2 group and the nimodipine-2 group. Changes of pCREB protein in rat's hippocampus were detected using immunohistochemistry and Western blotting assay.

RESULTSThe expression of pCREB was higher in the CZD-1 and nimodipine-1 group than in the model group, while it was significantly different in the CZD-2 and nimodipine-2 groups than in the model-2 group.

CONCLUSIONCZD could relieve the cognitive dysfunction in the epileptic model rats induced by everyday PTZ kindling or by dilantin through increasing the pCREB expression.

Animals ; Cognition Disorders ; chemically induced ; prevention & control ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Epilepsy ; chemically induced ; drug therapy ; metabolism ; Hippocampus ; drug effects ; metabolism ; pathology ; Kindling, Neurologic ; drug effects ; Male ; Pentylenetetrazole ; Phenytoin ; adverse effects ; Phosphorylation ; Phytotherapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the pretreatment effects of Rhodiola rosea (R. rosea) extract on cognitive dysfunction, oxidative stress in hippocampus and hippocampal neuron injury in a rat model of Alzheimer's disease (AD).

METHODSMale Sprague-Dawley rats were pretreated with R. rosea extract at doses of 1.5, 3.0, and 6.0 g/kg for 3 weeks, followed by bilateral intracerebroventricular injection with streptozotocin (1.5 mg/kg) on days 1 and 3. Behavioral alterations were monitored after 2 weeks from the lesion using Morris water maze task. Three weeks after the lesion, the rats were sacrificed for measuring the malondialdehyde (MDA), glutathione reductase (GR) and reduced glutathione (GSH) levels in hippocampus and histopathology of hippocampal neurons.

RESULTSThe MDA level was significantly increased while the GR and GSH levels were significantly decreased with striking impairments in spatial learning and memory and severe damage to hippocampal neurons in the model rat induced by intracerebroventricular injection of streptozotocin. These abnormalities were significantly improved by pretreatment with R. rosea extract (3.0 g/kg).

CONCLUSIONR. rosea extract can protect rats against cognitive deficits, neuronal injury and oxidative stress induced by intracerebroventricular injection of streptozotocin, and may be used as a potential agent in treatment of neurodegenerative diseases such as AD.

Animals ; Behavior, Animal ; drug effects ; Biomarkers ; metabolism ; Cell Count ; Cognition Disorders ; chemically induced ; drug therapy ; physiopathology ; Hippocampus ; drug effects ; pathology ; Injections, Intraventricular ; Male ; Neurons ; drug effects ; pathology ; Neuroprotective Agents ; pharmacology ; Oxidative Stress ; drug effects ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Rhodiola ; metabolism ; Streptozocin ; administration & dosage ; Swimming ; physiology