OBJECTIVEThe present study investigated the effects of rapamycin on Aβ1-42-induced deficits in working memory and synaptic plasticity.

METHODSAfter bilateral hippocampal injection of Aβ1-42 and rapamycinin rats, spontaneous alternation in Y-maze and in vivo hippocampal long-term potentiation (LTP) of rats were recorded. All data were analized by two-way repeated measures analysis of variance (ANOVA).

RESULTS(Hippocampal injection of Aβ1-42 alone impaired working memory of rats; (2) Rapamycin did not affect working memory of rats, but alleviated Aβ1-42-induced working memory deficits, compared with Aβ1-42 alone group; (Aβ1-42 remarkably suppressed in vivo hippocampal LTP of fEPSPs in the CA1 region; (4) Pretreatment with rapamycin prevented Aβ1-42-induced suppression of LTP.

CONCLUSIONThese data indicates that rapamycin could protect against Aβ1-42-induced impairments in working memory and synaptic plasticity in rats.

Amyloid beta-Peptides ; adverse effects ; Animals ; Hippocampus ; drug effects ; Long-Term Potentiation ; Maze Learning ; Memory, Short-Term ; drug effects ; Neuronal Plasticity ; drug effects ; Peptide Fragments ; adverse effects ; Rats ; Sirolimus ; pharmacology

PURPOSE: The purpose of this study was to evaluate the cognitive effects of chemotherapy in patients with breast cancer. METHODS: Using several databases, prospective studies were collected up to August 2011. Of 2,106 publications identified, 12 met the inclusion criteria, and 8 studies were used to estimate the effect size of chemotherapy on cognitive impairment. RESULTS: Twelve studies were done since 2005 and most of the research was performed in Europe or North America. Eight studies were used to generate effect size across the cognitive domains of attention/concentration, verbal and visual memory, executive function, visuospatial skill, language, and subjective cognitive function. Each of the cognitive domains showed small effect sizes (-0.02 ~ -0.26), indicating diminished cognitive function for the chemotherapy group compared with non-chemotherapy groups. CONCLUSION: Finding suggests that breast cancer patients who undergo chemotherapy may experience mild cognitive decline. Further study is needed to generate knowledge and guideline for interventions to address chemotherapy related cognitive impairment in these patients.
Antineoplastic Agents/adverse effects/*therapeutic use ; Breast Neoplasms/*drug therapy ; Cognition Disorders/*physiopathology ; Databases, Factual ; Female ; Humans ; Language Tests ; Memory, Short-Term ; Neuropsychological Tests

Valproic acid (VPA), an agent that is used to treat epileptic seizures, can cause spatial memory impairment in adults and children. This effect is thought to be due to the ability of VPA to inhibit neurogenesis in the hippocampus, which is required for learning. We have previously used an animal model to show that VPA significantly impairs hippocampal-spatial working memory and inhibits neuronal generation in the sub-granular zone of the dentate gyrus. As there are patient reports of improvements in memory after discontinuing VPA treatment, the present study investigated the recovery of both spatial memory and hippocampal neurogenesis at two time points after withdrawal of VPA. Male Wistar rats were given intraperitoneal injections of 0.9% normal saline or VPA (300 mg/kg) twice a day for 10 d. At 1, 30, or 45 d after the drug treatment, the novel object location (NOL) test was used to examine spatial memory; hippocampal cell division was counted using Ki67 immunohistochemistry, and levels of brain-derived neurotrophic factor (BDNF) and Notch1 were measured using western immunoblotting. Spatial working memory was impaired 1 and 30 d after the final administration, but was restored to control levels by 45 d. Cell proliferation had increased to control levels at 30 and 45 d. Both markers of neurogenesis (BDNF and Notch1 levels) had returned to control levels at 45 d. These results demonstrate that memory recovery occurs over a period of six weeks after discontinuing VPA treatment and is preceded by a return of hippocampal neurogenesis to control levels.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; Cell Proliferation ; Cognition/drug effects* ; Dentate Gyrus/drug effects* ; Enzyme Inhibitors/pharmacology* ; Hippocampus/metabolism* ; Immunohistochemistry ; Male ; Memory Disorders/therapy* ; Memory, Short-Term/drug effects* ; Neurogenesis/drug effects* ; Neurons/metabolism* ; Rats ; Rats, Wistar ; Receptor, Notch1/metabolism* ; Spatial Memory/drug effects* ; Valproic Acid/pharmacology*

OBJECTIVETo research Angelica tenuissima Nakai (ATN) for use in novel Alzheimer's disease (AD) therapeutics.

METHODSThe effect of a 30% ethanol extract of ATN (KH032) on AD-like cognitive impairment and neuropathological and neuroinflammatory changes induced by bilateral intracerebroventricular injections of β-amyloid (Aβ) peptide (Aβ) was investigated. Male C57Bl/6 mice were randomly divided into 4 groups, 10 in each group. KH032-treated groups were administrated with a low or high dose of KH032 (50 and 200 mg/kg, respectively), intragastrically for 16 days; distilled water was applied in the sham and negative groups. Open fifield test, Y maze and Morris water maze test were used for behavior test and cognitive ability. In addition, the neuroprotective effects of KH032 in Aβ-infused mice on the histopathological markers [neuronspecific nuclear protein (NeuN), Aβ] of neurodegeneration were examined. The levels of glial fibrillary acidic protein (GFAP), NeuN, phosphorylation extracellular signal-regulated kinase (ERK)/ERK, brain-derived neurotrophic factor (BDNF), phosphorylation cAMP response element-binding (CREB)/CREB protein expression were measured by Western blot.

RESULTSKH032 treatment ameliorated cognitive impairments, reduced the overexpression of Aβ, and inhibited neuronal loss and neuroinflammatory response in the Aβ-infused mice. Moreover, KH032 treatment enhanced BDNF expression levels in the hippocampus. Finally, KH032 treatment increased phosphorylation of ERK1/2 and CREB, vital for ERK-CREB signaling.

CONCLUSIONSKH032 attenuated cognitive defificits in the Aβ-infused mice by increasing BDNF expression and ERK1/2 and CREB phosphorylation and inhibiting neuronal loss and neuroinflflammatory response, suggesting that KH032 has therapeutic potential in neurodegenerative disorders such as AD.

Alzheimer Disease ; drug therapy ; pathology ; physiopathology ; Amyloid beta-Peptides ; Angelica ; chemistry ; Animals ; Brain ; pathology ; Brain-Derived Neurotrophic Factor ; metabolism ; Cognitive Dysfunction ; complications ; drug therapy ; physiopathology ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Disease Models, Animal ; Male ; Maze Learning ; drug effects ; Memory, Short-Term ; drug effects ; Mice, Inbred C57BL ; Neurogenesis ; drug effects ; Neuroglia ; drug effects ; metabolism ; pathology ; Neurons ; drug effects ; metabolism ; pathology ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Phosphorylation ; drug effects ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Plaque, Amyloid ; drug therapy ; pathology ; physiopathology ; Signal Transduction ; drug effects