We investigated the effects of hyperbaric oxygen treatment on the Nrf2 signaling pathway in secondary injury following traumatic brain injury, using a rat model. An improved Feeney freefall method was used to establish the rat traumatic brain injury model. Sixty rats were randomly divided into three groups: a sham surgery group, a traumatic brain injury group, and a group receiving hyperbaric oxygen treatment after traumatic brain injury. Neurological function scores were assessed at 12 and 24 h after injury. The expression levels of Nrf2, heme oxygenase 1 (HO-1), and quinine oxidoreductase 1 (NQO-1) in the cortex surrounding the brain lesion were detected by western blotting 24 h after the injury. Additionally, the TUNEL method was used to detect apoptosis of nerve cells 24 h after traumatic injury and Nissl staining was used to detect the number of whole neurons. Hyperbaric oxygen treatment significantly increased the expression of nuclear Nrf2 protein (P<0.05), HO-1, and NQO-1 in the brain tissues surrounding the lesion after a traumatic brain injury (P<0.05) and also significantly reduced the number of apoptotic and injured nerve cells. The neurological function scores also improved with hyperbaric oxygen treatment (P<0.05). Therefore, hyperbaric oxygen has a neuroprotective role in traumatic brain injury, which is mediated by up-regulation of the Nrf2 signaling pathway.

OBJECTIVE:To observe the influence of moxibustion on the cyclin and cellular proliferin of the cerebral cortex in senile mice so as to explore its underlying mechanism in delaying aging.

METHODS:Sixty male mice were randomly and equally divided into control, model, moxibustion of "Zusanli" (ST 36) and "Xuanzhong" (GB 39, M-ST 36-GB 39), moxibustion of "Baihui" (GV 20) and "Guanyuan" (CV 4,M-GV 20-COV 4) ,and medication groups. The aging model was established by subcutaneous injection of D-galactose for 42 days. Moxibustion was applied to ST 36, GB 39, GV 20 and CV 4 separately for 3 moxa-cones, once every other day for one month. The expression of cell cycle protein P 16 and retinoblastoma (pRb), and c-fos protein in the cerebral cortex tissue of the senile mice were detected by immunohistochemistry.

RESULTS:Compared with control group, the number of P16 immunoreaction (IR) positive neurons in the cerebral cortex increased significantly in the model group (P<0.01), and those of cortical pRb and c-fos IR-positive neurons decreased considerably in model group (P<0.01). In comparison with the model group, the number of cortical P 16 IR-positive neurons reduced significantly in M-ST 36-GB 39, M-GV 20-CV 4 and medication groups (P<0.01), and those of cortical pRb and c-fos IR-positive neurons increased remarkably in M-ST 36-GB 39, M-GV 20-CV 4 and medication groups (P<0.01, P<0.05). No significant differences were found in the aforementioned 3 indexes among M-ST 36-GB 39, M-GV 20-CV 4 and medication groups (P>0.05).

CONCLUSION:Moxibustion of ST 36-GB 39 and GV 20-CV 4 can down-regulate the P 16 expression,and up-regulate pRb and c-fos protein expression in the cerebral cortex of senile mice, which possibly contributes to its effect in delaying aging.

OBJECTIVE:To compare the therapeutic differences among scalp acupuncture combined with auricular point sticking, body acupuncture and western medication for treatment of vascular dementia (VD).

METHODS:Ninety cases were randomly divided into a combined therapy group (31 cases), a body acupuncture group (29 cases) and a western medication group (30 cases). The combined therapy group was treated with scalp acupuncture at forehead middle line, parieral middle line, temporal front line and temporal rear line as well as auricular point sticking at naogan (AT3,41), shen (CO10), shenmen (TF4), zhen (AT3), once a day; the body acupuncture group was treated with acupuncture at Baihui (GV 20), Fengchi (GB 20), Zusanli (ST 36) and so on, once a day; the western medication group was treated with oral administration of aniracetam tablets, 0.2 g per time, twice a day. Fourteen days were considered as a treatment course, and totally 3 courses were required. The mini-mental state examination (MMSE) and activities of daily living (ADL) were applied to assess the changes of cognitive behavior ability before and after treatment among three groups. Also the efficacy among three groups were compared.

RESULTS:One case dropped out in the body acupuncture group and western medication group, respectively. The total effective rate was 90.334 (28/31) in the combined therapy group, which was superior to 85.734 (24/28) in the body acupuncture group and 79.3% (23/29) in the western medication group (both P<0.05). After the treatment, the scores of MMSE and ADL were all improved among three groups, which was the most significant in the combined therapy group (MMSE: 23.32 +/- 4.45 vs 21.23 +/- 4.13, P<0.05; 23.32 +/- 4.45 vs 20.41 +/- 4. 01, P<0.01; ADL: 53.18 +/- 21.55 vs 51.92 +/- 20.42, P<0.05; 53.18 +/- 21.55 vs 49.42 +/- 19.43, P<0.01).

CONCLUSION:The scalp acupuncture combined with auricular point sticking could improve the clinical symptoms and cognitive behavior ability in patients with vascular dementia, which has superior total efficacy to body acupuncture and western medication aniracetam tablets.

OBJECTIVE:To compare the therapeutic differences among scalp acupuncture combined with auricular point sticking, body acupuncture and western medication for treatment of vascular dementia (VD).

METHODS:Ninety cases were randomly divided into a combined therapy group (31 cases), a body acupuncture group (29 cases) and a western medication group (30 cases). The combined therapy group was treated with scalp acupuncture at forehead middle line, parieral middle line, temporal front line and temporal rear line as well as auricular point sticking at naogan (AT3,41), shen (CO10), shenmen (TF4), zhen (AT3), once a day; the body acupuncture group was treated with acupuncture at Baihui (GV 20), Fengchi (GB 20), Zusanli (ST 36) and so on, once a day; the western medication group was treated with oral administration of aniracetam tablets, 0.2 g per time, twice a day. Fourteen days were considered as a treatment course, and totally 3 courses were required. The mini-mental state examination (MMSE) and activities of daily living (ADL) were applied to assess the changes of cognitive behavior ability before and after treatment among three groups. Also the efficacy among three groups were compared.

RESULTS:One case dropped out in the body acupuncture group and western medication group, respectively. The total effective rate was 90.334 (28/31) in the combined therapy group, which was superior to 85.734 (24/28) in the body acupuncture group and 79.3% (23/29) in the western medication group (both P<0.05). After the treatment, the scores of MMSE and ADL were all improved among three groups, which was the most significant in the combined therapy group (MMSE: 23.32 +/- 4.45 vs 21.23 +/- 4.13, P<0.05; 23.32 +/- 4.45 vs 20.41 +/- 4. 01, P<0.01; ADL: 53.18 +/- 21.55 vs 51.92 +/- 20.42, P<0.05; 53.18 +/- 21.55 vs 49.42 +/- 19.43, P<0.01).

CONCLUSION:The scalp acupuncture combined with auricular point sticking could improve the clinical symptoms and cognitive behavior ability in patients with vascular dementia, which has superior total efficacy to body acupuncture and western medication aniracetam tablets.

Extracts of Ginkgo biloba leaves, a natural source of flavonoids and polyphenolic compounds, are commonly used as therapeutic agents for the improvement of both cognitive and physiological performance. The present study was aimed to test the effects of a six-week supplementation with 160 mg/day of a standardized extract of Ginkgo biloba or a matching placebo on aerobic performance, blood antioxidant capacity, and brain-derived neurotrophic factor (BDNF) level in healthy, physically active young men, randomly allocated to two groups (n = 9 each). At baseline, as well as on the day following the treatment, the participants performed an incremental cycling test for the assessment of maximal oxygen uptake. Venous blood samples taken at rest, then immediately post-test and following 1 h of recovery, were analyzed for activities of antioxidant enzymes and plasma concentrations of non-enzymatic antioxidants, total phenolics, uric acid, lipid peroxidation products, ferric reducing ability of plasma (FRAP), and serum brain-derived neurotrophic factor (BDNF). Our results show that six weeks' supplementation with Ginkgo biloba extract in physically active young men may provide some marginal improvements in their endurance performance expressed as VO₂max and blood antioxidant capacity, as evidenced by specific biomarkers, and elicit somewhat better neuroprotection through increased exercise-induced production of BDNF.

BACKGROUND:Traumatic brain injury (TBI) is accompanied by substantial accumulation of biomarkers of oxidative stress and depletion of antioxidants reserve which initiate chain reactions that damage brain cells. The present study investigated the role of ascorbic acid andα-tocopherol on the severity and management of TBI in rats.

MATERIALS AND METHODS:Wistar rats were subjected to closed head injury using an accelerated impact device. Rats were administered 45 mg/kg and 60 mg/kg body weight of ascorbic acid,α-tocopherol or a combination of the two vitamins for 2 weeks pre- and post injury. Blood and brain tissue homogenates were analyzed for vitamin C, vitamin E, malondialdehyde, superoxide dismutase, and creatine kinase activities.

RESULTS:The results indicated that TBI caused significant (P<0.05) decreased in vitamins C and E levels in the blood and brain tissue of TBI-untreated rats. The activities of superoxide dismutase in TBI rats were markedly reduced when compared with non traumatized control and showed a tendency to increased following supplementation with vitamins C and E. Supplementation of the vitamins significantly (P<0.05) reduced malondialdehyde in the treatment groups compared with the TBI-untreated group.

CONCLUSION:The study indicated that pre and post treatment with ascorbic acid andα-tocopherol reduced oxidative stress induced by brain injury and effectively reduced mortality rate in rats.

In the present study, we evaluated the curative effect of dipeptidyl peptidase-IV (DPP-IV) inhibitor alogliptin combined with motor imagery under hyperbaric oxygen in diabetic nephropathy (DN) with silent cerebral infarction (SCI). Two-hundred newly diagnosed DN patients with and without SCI were included. The SCI patients were divided into two treatment groups: Alogliptin (A group, n=50) and alogliptin combined with motor imagery under hyperbaric oxygen (B group, n=50). The degrees of neurocognitive dysfunction were evaluated at baseline and after 6 months of treatment. Thromboelastograms (TEGs) mapping were conducted. Serum glycoprotein VI (GPVI) mRNA expression and urine 11-DH-TXB2 levels were determined. Compared to group A patients, the severity of neurofunctional defects, GPVI mRNA expression and 11-DH-TXB2 levels were significantly lower in group B (P<0.05), while comprehensive, MoCA scores were higher in group B. The MoCA subscores of visuospatial/executive function, attention and concentration were significantly higher compared to group A (P<0.05). The sub-scores of computation, abstract thinking, language competence, memory and orientation were also higher in group B but the differences were not significant (P>0.05). TEG indexes were improved in both groups after treatment as manifested by increased R and K values, but there was significant improvement in group B. Intra-group comparisons revealed a time-dependent effect of treatment. In conclusion, the treatment of alogliptin combined with motor imagery under hyperbaric oxygen can better promote thrombolysis absorption, restore brain damage and improve neurocognitive function in DN with silent cerebral infarction.

OBJECTIVE:After MRI studies suggested the efficacy of ethyl-EPA in reducing the progressive brain atrophy in Huntington disease, trials were conducted to test its efficacy as a treatment for Huntington disease. Trials continued for six months did not find any significant improvement urging discontinuation of the drug. However, trials continued for 12 months indicated improvement of motor functions in these patients.

METHODS:We searched 12 electronic databases to find randomized clinical trials relevant to our inclusion criteria. After screening, only five papers were included. Continuous and binary variables were analyzed to compute the pooled mean difference (MD) and risk ratio (RR), respectively. Quality effect model meta-analysis was used as a post hoc analysis for studies at 12 months.FindingsMeta-analysis indicated that ethyl-eicosapentaenoic acid has no significant effect on any scale of HD at six months. At 12 months, two studies suggested significant improvements of the total motor score and total motor score -4 in both fixed and quality effect model [MD = -2.720, 95% CI (-4.76; -.68), P = 0.009], [MD = -2.225, 95% CI (-3.842; -0.607), P = 0.007] respectively. maximal chorea score showed significant results [MD = -1.013, 95% CI (-1.793; -0.233), P = 0.011] in only fixed effect model, while no improvement was detected for Stroop color naming test or symbol digit modality.

CONCLUSION:Meta-analysis indicated a significant improvement of motor scores only after 12 months. These results should be interpreted cautiously because only two studies had assessed the efficacy of ethyl-EPA after 12 months with one of them having six months open-label phase.

Electroacupuncture (EA) administration before or after cerebral ischemia has been shown to afford protection against ischemic injury. However, the underlying mechanism of EA-mediated protection is still unclear. Functional microRNAs (miRNAs) are believed to play important roles in neuroprotection and synaptic plasticity during and after ischemia. In a previous study, we identified 20 miRNAs that are expressed in the penumbra and are significantly changed after EA treatment. Here, we used bioinformatics analysis to predict the biological functions and gene-networks of these miRNAs. Consistent with our predictions, down-regulation of miR-191a-5p in primary neurons and in cortexes of rats increased cell viability, decreased apoptosis, reduced infarct volumes, and improved neurological scores; whereas up-regulation of miR-191a-5p exacerbated neuronal injury and partly reversed the neuroprotective effect of EA treatment after ischemia/repercussion injury. In silico analysis predicted that miR-191a-5p targets Neuronal calcium sensor 1 (NCS-1), brain-derived neurotrophic factor (BDNF) and growth associated protein 43 (GAP43), and using luciferase reporter assays, we confirmed that the NCS-1 3'UTR is targeted by miR-191a-5p. Furthermore, lentivirus-mediated overexpression of NCS-1 in primary neurons and in the cortexes of rats induced neuroprotection, while lentivirus-mediated knockdown had the opposite effect. Taken together, these data suggest that miRNAs participate in the response to EA treatment after cerebral ischemia and further imply that NCS-1 may constitute a miR-191a-5p target gene and a potential therapeutic target for neuroprotection.

Accumulating evidence demonstrates that acupuncture and electroacupuncture (EA) can exert a neuroprotective role for cerebral ischemia, but their precise mechanism remains largely unknown. Therefore, in this study, the effects of EA stimulation on cerebral ischemia reperfusion and its neuroprotective mechanisms were investigated. A rat model of middle cerebral artery occlusion (MCAO) was developed, and EA stimulation (2Hz, 1mA) at Baihui and Siguan acupoints was applied 30min after MCAO and then once daily for 7 consecutive days. The results indicated that EA stimulation significantly reduced the cerebral infarct area and neurological deficit scores, decreased the number of apoptotic cells, up-regulated Bcl-2 protein expression, and down-regulated Bax protein expression. EA stimulation resulted in a significant increase of proliferative cells in the cerebral tissues. Additionally, EA stimulation significantly down-regulated the expression levels of matrix metalloproteinase -9 (MMP-9) mRNA and protein, and simultaneously up-regulated the expression levels of tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA and protein, which resulted in an imbalance of MMP-9/TIMP-1expression, although it did not significantly change MMP-2 and TIMP-2 expression. These findings indicate that EA stimulation at Baihui and Siguan acupoints exerts a neuroprotective role against cerebral ischemia-reperfusion injury, which is probably associated with the inhibition of apoptosis and altering the balance of MMP-9/TIMP-1 expression.

Background. The therapeutic mechanisms of cerebral ischemia treatment by acupuncture are yet not well addressed. Objective. We investigated the effects of electroacupuncture (EA) at GV26 observing the expression of autophagy-related proteins Beclin-1 and LC3B and proportion of apoptotic cells and Bcl-2 positive cells in MCAO/R model rats. Methods. Sprague-Dawley (SD) male rats were randomly assigned to 7 groups: model groups (M6h, M24h, and M72h), EA treatment groups (T6h, T24h, and T72h), and sham operation group (S). Neurological deficit and cerebral infarction volume were measured to assess the improvement effect, while the expression of Beclin-1 and LC3B and proportion of Tunel-positive and Bcl-2 positive cells were examined to explore EA effect on autophagy and apoptosis. Results. EA significantly decreased neurological deficit scores and the volume of cerebral infarction. Beclin-1 was significantly decreased in T24h, while LC3B-II/LC3B-I ratio markedly reduced in 6th hour. EA groups markedly reduced the number of Tunel positive cells, especially in T24h. Meanwhile, the number of Bcl-2 positive cells obviously increased after EA treatment, especially in T6h and T24h. Conclusions. The alleviation of inadequate autophagy and apoptosis may be a key mechanism involved in the reflex regulation of EA at GV26 to treat cerebral ischemia.

Spontaneous intracerebral hemorrhage (ICH) is one of the most devastating types of stroke. Here, we aim to demonstrate that electroacupuncture on Baihui (GV20) exerts neuroprotection for acute ICH possibly via the caveolin-1/matrix metalloproteinase/blood-brain barrier permeability pathway. The model of ICH was established by using collagenase VII. Rats were randomly divided into three groups: Sham-operation group, Sham electroacupuncture group, and electroacupuncture group. Each group was further divided into 4 subgroups according to the time points of 6 h, 1 d, 3 d, and 7 d after ICH. The methods were used including examination of neurological deficit scores according to Longa's scale, measurement of blood-brain barrier permeability through Evans Blue content, in situ immunofluorescent detection of caveolin-1 in brains, western blot analysis of caveolin-1 in brains, and in situ zymography for measuring matrix metalloproteinase-2/9 activity in brains. Compared with Sham electroacupuncture group, electroacupuncture group has resulted in a significant improvement in neurological deficit scores and in a reduction in Evans Blue content, expression of caveolin-1, and activity of matrix metalloproteinase-2/9 at 6 h, 1 d, 3 d, and 7 d after ICH (P<0.05). In conclusion, the present results suggested that electroacupuncture on GV20 can improve neurological deficit scores and reduce blood-brain barrier permeability after ICH, and the mechanism possibly targets caveolin-1/matrix metalloproteinase/blood-brain barrier permeability pathway.

Acupuncture has been widely used as a treatment for stroke in China for a long time. Recently, studies have demonstrated that electroacupuncture (EA) can accelerate intracerebral hemorrhage (ICH)-induced angiogenesis in rats. In the present study, we investigated the effect of EA on neurobehavioral function and brain injury in ICH rats. ICH was induced by stereotactic injection of collagenase type I and heparin into the right caudate putamen. Adult ICH rats were randomly divided into the following three groups: model control group (MC), EA at non-acupoint points group (non-acupoint EA) and EA at Baihui and Dazhui acupoints group (EA). The neurobehavioral deficits of ICH rats were assessed by modified neurological severity score (mNSS) and gait analysis. The hemorrhage volume and glucose metabolism of hemorrhagic foci were detected by PET/CT. The expression levels of MBP, NSE and S100-B proteins in serum were tested by ELISA. The histopathological features were examined by haematoxylin-eosin (H&E) staining. Apoptosis-associated proteins in the perihematomal region were observed by immunohistochemistry. EA treatment significantly promoted the recovery of neurobehavioral function in ICH rats. Hemorrhage volume reduced in EA group at day 14 when compared with MC and non-acupoint EA groups. ELISA showed that the levels of MBP, NSE and S100-B in serum were all down-regulated by EA treatment. The brain tissue of ICH rat in the EA group was more intact and compact than that in the MC and non-acupoint groups. In the perihematomal regions, the expression of bcl-2 protein increased and expressions of caspase-3 and bax proteins decreased in the EA group vs MC and non-acupoint EA groups. Our data suggest that EA treatment can improve neurobehavioral function and brain injury, which were likely connected with the absorption of hematoma and regulation of apoptosis-related proteins.

Sepsis is associated with high morbidity and mortality. This study was to investigate the protective effects of electroacupuncture (EA) pretreatment with different waveforms on septic brain injury in rats and its mechanism. Male Sprague-Dawley rats were pretreated by EA with different waveforms (continuous wave, dilatational wave, or intermittent wave) at Baihui (GV20) and Tsusanli (ST36) acupoints for 30min, and underwent cecal ligation and puncture (CLP) or sham operation. The results showed that EA pretreatment with different waveforms improved survival rate, attenuated encephaledema, brain injury, neuronal apoptosis and cognitive dysfunction, and preserved blood-brain barrier (BBB). EA pretreatment decreased the production of tumor necrosis factor(TNF)-α, interleukin(IL)-6, malondialdehyde (MDA), and increased the activity of superoxide dismutase (SOD) and catalase (CAT) in serum and hippocampus at 48h after sham or CLP operation. Additionally, EA pretreatment downregulated the expressions of toll-like receptor-4 (TLR-4), nuclear factor-kappa B (NF-κB) and ionized calcium binding adaptor molecule 1(Iba 1). The effect of dilatational wave was the most significant, followed by intermittent wave, and continuous wave was relatively poor. In conclusion, our results demonstrate that EA pretreatment with three waveforms alleviates sepsis-inducedbrain injury by inhibition of microglial activation and attenuation of inflammation, oxidative stress and apoptosis. These findings suggest that EA pretreatment with dilatational wave at Baihui and Tsusanli acupoints might be a promising therapeutic strategy for relieving septic brain injury.

Parkinson's disease (PD) is a common neurodegenerative disease. The pathological hallmark of PD is a progressive loss of dopaminergic neurons in the substantia nigra (SN) pars compacta in the brain, ultimately resulting in severe striatal dopamine deficiency and the development of primary motor symptoms (e.g., resting tremor, bradykinesia) in PD. Acupuncture has long been used in traditional Chinese medicine to treat PD for the control of tremor and pain. Accumulating evidence has shown that using electroacupuncture (EA) as a complementary therapy ameliorates motor symptoms of PD. However, the most appropriate timing for EA intervention and its effect on dopamine neuronal protection remain unclear. Thus, this study used the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model (systemic-lesioned by intraperitoneal injection) and the 1-methyl-4-phenylpyridinium (MPP⁺)-lesioned rat model (unilateral-lesioned by intra-SN infusion) of PD, to explore the therapeutic effects and mechanisms of EA at the GB34 (Yanglingquan) and LR3 (Taichong) acupoints. We found that EA increased the latency to fall from the accelerating rotarod and improved striatal dopamine levels in the MPTP studies. In the MPP⁺ studies, EA inhibited apomorphine induced rotational behavior and locomotor activity, and demonstrated neuroprotective effects via the activation of survival pathways of Akt and brain-derived neurotrophic factor (BDNF) in the SN region. In conclusion, we observedthat EA treatment reduces motor symptoms of PD and dopaminergic neurodegeneration in rodent models, whether EA is given as a pretreatment or after the initiation of disease symptoms. The results indicate that EA treatment may be an effective therapy for patients with PD.

Inflammation after stroke is the main cause of cerebral ischemia/reperfusion injury. Cascading events after injury can lead to cell death. Heat shock protein 70 and other endogenous injury-signaling molecules are released by damaged cells, which can lead to systemic stress reactions. Protecting the brain through repair begins with the stress-injury-repair signaling chain. This study aimed to verify whether acupuncture acts through this chain to facilitate effective treatment of ischemic stroke. Rat models of cerebral ischemia/reperfusion injury were established by Zea Longa's method, and injury sites were identified by assessing neurological function, 2,3,5-triphenyltetrazolium chloride staining, and hematoxylin-eosin staining. Electroacupuncture at acupoints Baihui (DU20) and Zusanli (ST36) was performed in the model rats with dilatational waves, delivered for 20 minutes a day at 2-100 Hz and an amplitude of 2 mA. We analyzed the blood serum from the rats and found that inflammatory cytokines affected the levels of adrenotrophin and heat shock protein 70, each of which followed a similar bimodal curve. Specifically, electroacupuncture lowered the peak levels of adrenocorticotrophic hormone and heat shock protein 70. Thus, electroacupuncture was able to inhibit excessive stress, reduce inflammation, and promote the repair of neurons, which facilitated healing of ischemic stroke.

is a white-rot fungus that has been viewed as a traditional Chinese tonic for promoting health and longevity. It has been revealed that several extractions from, such as Ethanol extract, aqueous extract, mycelia extract, water soluble extract of the culture medium ofmycelia, Ganodermasides A, B, C, D, and some bioactive components of, including Reishi Polysaccharide Fraction 3,polysaccharides I, II, III, IV,peptide,polysaccharide peptide, totaltriterpenes and Ganoderic acid C1 could exert lifespan elongation or related activities. Although the use ofas an elixir has been around for thousands of years, studies revealing its effect of lifespan extension are only the tip of the iceberg. Besides which, the kinds of extractions or components being comfrimed to be anti-aging are too few compared with the large amounts ofextractions or constituients being discovered. This review aims to lay the ground for fully elucidating the potential mechanisms ofunderlying anti-aging effect and its clinical application.

BACKGROUND:Epidemiological evidence suggests that exercise and dietary polyphenols are beneficial in reducing Alzheimer's disease (AD) risk.

MATERIALS AND METHODS:In the present study, 8 months old amyloid precursor protein/presenilin 1 (APP/PS1) mice (a moderate pathology phase) were given the green tea catechin (-)-epicatechin delivered orally in the drinking water (50 mg/kg daily), along with treadmill exercise for 4 months, in order to investigate whether the combination can ameliorate the cognitive loss and delay the progression of AD in APP/PS1 transgenic (Tg) mice.

RESULTS:At termination, untreated-Tg mice showed elevated soluble amyloid-β (Aβ1-40) and Aβ1-42 levels and deficits in spatial learning and memory, compared with their wild-type littermates. The combined intervention protected against cognitive deficits in the Morris water maze, lowered soluble Aβ1-40 and Aβ1-42 levels in the hippocampus as well as reducing brain oxidative stress. In addition, brain-derived neurotrophic factor proteins wee elevated and Akt/GSK-3/cAMP response element-binding protein signaling was activated in the combination group.

CONCLUSIONS:Dietary polyphenol plus exercise may exert beneficial effects on brain health and slow the progression of moderate- or mid-stages of AD.

SUMMARY:Amyloid precursor protein/presenilin 1 transgenic mice showed elevated soluble amyloid-β (Aβ1-40) and Aβ1-42 levels and deficits in spatial learning and memory, compared with their wild-type littermatesOral administration of epicatechin, combined with treadmill exercise for 4 months, could protect against cognitive deficits, and lowered soluble Aβ1-40 and Aβ1-42 levels as well asreducing brain oxidative stressBrain-derived neurotrophic factor proteins were elevated, and Akt/GSK-3/cAMP response element binding protein signaling was activated in the combination groupDietary polyphenol plus exercise might exert beneficial effects on brain health and slow the progression of moderate- or mid-stages of Alzheimer's disease. Abbreviations used: AD: Alzheimer's disease, Tg: APP/PS1 transgenic, BDNF: Brain-derived neurotrophic factor, Aβ: Amyloid-β, APP: Amyloid precursor protein, PS1: Presenilin 1, nTg: Wild-type littermates, IACUC: Institutional Animal Care and Use Committee, GSSG: Glutathione oxidized form, GSH: Glutathione reductase, SOD: Superoxide dismutase, CAT: Catalase, LPO: Lipoperoxidation, CREB: cAMP response element binding protein.

Huntington's disease (HD) is an inherited, progressive and ultimately fatal neurodegenerative disorder that is characterized by psychiatric, cognitive and motor symptoms. Among the pathways implicated in HD are those involving mitogen-activated protein kinase signaling and particularly the Ras-extracellular signal-regulated kinase (ERK) cascade. Studies in both cells and animal models suggest that ERK activation might provide a novel therapeutic target for the treatment of HD but compounds that specifically activate ERK are few. To test the hypothesis that pharmaceutical activation of ERK might be protective for HD, a polyphenol, fisetin, which was previously shown to activate the Ras-ERK cascade, was tested in three different models of HD: PC12 cells expressing mutant Httex1 under the control of an inducible promoter, Drosophila expressing mutant Httex1 and the R6/2 mouse model of HD. The results indicate that fisetin can reduce the impact of mutant huntingtin in each of these disease models. Prompted by this observation, we determined that the related polyphenol, resveratrol, also activates ERK and is protective in HD models. Notably, although more than a dozen small molecule inhibitors of ERK activation are in clinical trials, very few small molecule activators of ERK signaling are reported. Thus, fisetin, resveratrol and related compounds might be useful for the treatment of HD by virtue of their unique ability to activate ERK.

Huntington disease (HD) is a relentlessly progressive neurodegenerative disorder with symptoms across a wide range of neurological domains, including cognitive and motor dysfunction. There is still no causative treatment for HD but environmental factors such as passive lifestyle may modulate disease onset and progression. In humans, multidisciplinary rehabilitation has a positive impact on cognitive functions. However, a specific role for exercise as a component of an environmental enrichment effect has been difficult to demonstrate. We aimed at investigating whether endurance training (ET) stabilizes the progression of motor and cognitive dysfunction and ameliorates cardiovascular function in HD patients. Twelve male HD patients (mean ± SD, 54.8 ± 7.1 years) and twelve male controls (49.1 ± 6.8 years) completed 26 weeks of endurance training. Before and after the training intervention, clinical assessments, exercise physiological tests, and a body composition measurement were conducted and a muscle biopsy was taken from M. vastus lateralis. To examine the natural course of the disease, HD patients were additionally assessed 6 months prior to ET. During the ET period, there was a motor deficit stabilization as indicated by the Unified Huntington's Disease Rating Scale motor section score in HD patients (baseline: 18.6 ± 9.2, pre-training: 26.0 ± 13.7, post-training: 26.8 ± 16.4). Peak oxygen uptake ([Formula: see text]) significantly increased in HD patients (∆[Formula: see text] = +0.33 ± 0.28 l) and controls (∆[Formula: see text] = +0.29 ± 0.41 l). No adverse effects of the training intervention were reported. Our results confirm that HD patients are amenable to a specific exercise-induced therapeutic strategy indicated by an increased cardiovascular function and a stabilization of motor function.