No abstract

(−)-Epigallocatechin-3-gallate (EGCG) is the most widely studied catechin in green tea and has been identified to regulate immune function. The objective of the present study was to explore the possible application of EGCG in the treatment of Parkinson's disease (PD) by examining its effects on the peripheral immune system in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. The results demonstrated that EGCG treatment restored the movement behavior of the mice impaired by MPTP, and protected tyrosine hydroxylase-positive cells in the substantia nigra pars compacta region from MPTP toxicity. Flow cytometric analysis indicated that the ratio of CD3+CD4+ to CD3+CD8+ T lymphocytes in the peripheral blood increased in MPTP-treated mice following treatment with EGCG, and EGCG reduced expression of inflammatory factors tumor necrosis factor-α and interleukin-6 in serum. The present findings indicated that EGCG serves neuroprotective effects in an MPTP-induced PD mice model and may exert this through modulating peripheral immune response.

Glutamate excitotoxicity has been implicated as one of the pathological mechanisms contributing to neuronal cell death and is involved in many neurological disorders. Stem cell transplantation is a promising approach for the treatment of nervous system damage or diseases. Previous studies have shown that mesenchymal stem cells (MSCs) have important therapeutic effects in experimental animal and preclinical disease model of central nervous system pathology. However, it is not well understood whether neurogenesis of MSCs or MSC conditioned-medium (CM) containing microparticles mediates therapeutic effects. Here, we investigated the neuroprotective effects of human adipose-derived MSCs (AMSCs) on cortical neurons using models of glutamate excitotoxicity. Following exposure to glutamate (100 μM, 15 min), cortical neurons were co-cultured with either AMSCs separated by a semiporous membrane (prohibiting direct cell-cell contact) or with AMSC-CM for 18 h. Compared to untreated control groups, AMSCs and AMSC-CM partially and similarly reduced neuronal cell damages, as indicated by reduced LDH release, a decreased number of trypan-positive cells and a decline in the number of apoptotic nuclei. Protection by CM was associated with increased GAP-43 expression and an elevated number of GAP-43-positive neurites. Furthermore, CM increased levels of ATP, NAD+ and NADH and the ratio of NAD+/NADH, while preventing a glutamate-induced decline in mitochondrial membrane potential. These results demonstrate that AMSC-CM mediates direct neuroprotection by inhibiting neuronal cell damage/apoptosis, promoting nerve regeneration and repair, and restoring bioenergy following energy depletion caused by glutamate excitotoxicity.

Primary blepharospasm (BPS) is a focal dystonia characterized by involuntary blinking and eyelid spasms. The pathophysiology of BPS remains unclear. Several neuroimaging studies have suggested dysfunction of sensory processing and sensorimotor integration, but the results have been inconsistent. This study aimed to determine whether patients with BPS exhibit altered functional brain connectivity and to explore possible correlations between these networks and clinical variables. Twenty-five patients with BPS and 25 healthy controls were enrolled. We found that the patient group exhibited decreased connectivity within the sensory-motor network (SMN), which involved regions of the bilateral primary sensorimotor cortex, supplementary motor area (SMA), right premotor cortex, bilateral precuneus and left superior parietal cortex. Within the right fronto-parietal network, decreased connections were observed in the middle frontal gyrus, dorsal lateral prefrontal cortex and inferior frontal gyrus. Regarding the salience network (SN), increased connectivity was observed in the left superior frontal gyrus and middle frontal gyrus. These findings suggest the involvement of multiple neural networks in primary BPS.

Naringenin is a flavonoid polyphenolic compound, which facilitates the removal of free radicals, oxidative stress and inflammation. The present study aimed to obtain a better understanding of the effects of curcumin on the regulation of diabetes‑associated cognitive decline, and its underlying mechanisms. An experimental diabetes mellitus (DM) rat model was induced by streptozoticin (50 mg/kg). Following treatment with naringin (100 and 200 mg/kg) for 16 weeks, the body weight and blood glucose levels of the DM rats were measured. A morris water maze test was used to analyze the effects of naringin on the cognitive deficit of the DM rats. The levels of oxidative stress, proinflammatory factors, caspase‑3 and caspase‑9, and the protein expression of peroxisome proliferator‑activated receptor γ (PPARγ) were quantified in the DM rats using a commercially‑available kit and western blot assay, respectively. In addition, a GW9662 PPARγ inhibitor (0.3 mg/kg) was administered to the DM rats to determine whether PPARγ affected the effects of naringin on the cognitive deficit of the DM rats. The results demonstrated that naringin increased the body weight, blood glucose levels, and cognitive deficits of the DM rats. The levels of oxidative stress and proinflammatory factors in the naringin‑treated rats were significantly lower, compared with those of the DM rats. In addition, naringin activated the protein expression of PPARγ, and administration of the PPARγ inhibitor decreased the protein expression of PPARγ, and attenuated the effects of naringin on cognitive deficit. The results also demonstrated that naringin decreased the expression levels of caspase‑3 and caspase‑9 in the DM rats. These results suggested that naringin ameliorated cognitive deficits via oxidative stress, proinflammatory factors and the PPARγ signaling pathway in the type 2 diabetic rat model. Furthermore, oxidative stress, proinflammatory factors and PPARγ signaling may be involved in mediating these effects.

No abstract

In order to develop a cell-based vaccine against the Parkinson disease (PD) associated protein a-synuclein (a-Syn) 3 peptides were synthesized based upon predicted B cell epitopes within the full length a-Syn protein sequence. These peptide fragments as well as the full length recombinant human a-Syn (rh-a-Syn) protein were used to sensitize mouse bone marrow-derived dendritic cells (DC) ex vivo, followed by intravenous delivery of these sensitized DCs into transgenic (Tg) mice expressing the human A53T variant of a-Syn. ELISA analysis and testing of behavioral locomotor function by rotometry were performed on all mice after the 5th vaccination as well as just prior to euthanasia. The results indicated that vaccination with peptide sensitized DCs (PSDC) as well as DCs sensitized by rh-a-Syn induced specific anti-a-Syn antibodies in all immunized mice. In terms of rotometry performance, a measure of locomotor activity correlated to brain dopamine levels, mice vaccinated with PSDC or rh-a-Syn sensitized DCs performed significantly better than non-vaccinated Tg control mice during the final assessment (i.e. at 17 months of age) before euthanasia. As well, measurement of levels of brain IL-1a, a cytokine hypothesized to be associated with neuroinflammation, demonstrated that this proinflammatory molecule was significantly reduced in the PSDC and rha-Syn sensitized DC vaccinated mice compared to the non-vaccinated Tg control group. Overall, a-Syn antigensensitized DC vaccination was effective in generating specific anti-a-Syn antibodies and improved locomotor function without eliciting an apparent general inflammatory response, indicating that this strategy may be a safe and effective treatment for PD.

Sensory Guillain-Barré syndrome (GBS) is an acute demyelinating neuropathy that presents clinically with involvement of the sensory peripheral nerve only. To date, <10 cases of pure sensory GBS have been reported; thus, the clinical and pathological features of sensory variant GBS are yet to be well characterized. The current study reports the case of a 43-year-old female that presented with acute, symmetric and monophasic sensory neuropathy, without motor weakness. Patient history, clinical examination, routine nerve conduction studies and sural nerve biopsy were reviewed. All the observations were consistent with a diagnosis of pure sensory GBS. In particular, the pathological features of the sural nerve biopsy revealed that the form of regenerated nerve fibers have complete structure of myelinated nerve fascicles, and these myelinated nerve fibers are thicker than other parts of the biopsy. The patient received small-dose (20 mg/day) prednisone initially, but without any benefit. Satisfactory improvements were observed with one course of intravenous immunoglobulin.