Springer Science and Business Media LLC

Alzheimer’s disease (AD) is a syndrome caused by a few uncommon mutations that lead to early-onset disease, occurs in adults with Down’s syndrome, but is by far most commonly seen as a late-onset disease with multiple risk factors but no causative factors yet identified. Emerging data suggests a chronic disease model for AD with latency, prodrome, and dementia stages together lasting decades. Free radical damage to lipids in brain is one pathogenic process of AD that may be quantified with F2-isoprostanes (IsoPs). Whereas brain and cerebrospinal fluid (CSF) F2-IsoPs are reproducibly elevated in AD patients at both dementia and prodromal stages of disease, plasma and urine F2-IsoPs are not reproducibly increased in AD patients. CSF F2-IsoPs may be used to assist in diagnosis and aid in objective assessment of disease progression and response to therapeutics in patients with AD.

Spinal cord injury (SCI) is known as a debilitating condition which usually occurs due to traumas to the spine. However, the injury could also occur during clinical interventions such as spinal deformity and thoracoabdominal aortic surgeries. Intraoperative cord compression and ischemia are considered the mechanisms of primary injury in this regard. In the current study, we aimed to evaluate the therapeutic effects of minocycline, a promising agent for post-injury treatment, prophylactic administration. In a rat model of SCI through contusion injury, T9 vertebra laminectomy was performed on 40 Sprague–Dawley male rats provided from Pasteur Institute (Tehran, Iran). The reason behind selecting only male rats in our study was the fact that menstrual cycle of female rats affects healing process. Rodents were divided into a sham-operated group, a control group receiving only saline, a minocycline-treated group, and a minocycline pretreated group. Locomotor scaling, behavioral tests for neuropathic pain, and weight changes were evaluated and compared through a 28-days period. At the end of the study, tissue samples were taken to assess neuroinflammatory cytokine and histopathological changes. Minocycline pretreatment was as effective as its post-SCI administration regarding locomotor activity recovery, mechanical pain, and thermal allodynia. Furthermore, spinal cord inflammation and histopathological alterations were both similar in pretreatment and treatment groups indicating substantially better status. None of the treatments could have completely restore or prevent the spinal cord damage. Minocycline pretreatment can show promising therapeutic effects similar to its post-injury administration, inhibiting inflammatory microglial activity.

Several lines of evidence have suggested that the GABA receptor subunit β3 (GABRB3) gene is a genetic contributor in the autism spectrum disorder (ASD). The aberrant expression of GABRB3 is reported in ASD patients which may be a consequence of the presence of certain genetic variants in the promoter region of the gene. The associations between single-nucleotide polymorphisms (SNPs) within this gene and ASD have been analyzed in previous studies. However, the results are conflicting. In the present study, we performed a meta-analysis on association between two SNPs located in the promoter region of GABRB3 gene (rs4906902 and rs20317) and ASD. The literature search was performed based on criteria provided by the meta-analysis of observational studies in epidemiology (MOOSE). The association between mentioned SNPs and ASD was calculated using pooled odd ratios (ORs) and 95% confidence intervals. The result of the present meta-analysis indicates that neither rs4906902 nor rs20317 are significantly associated with the risk of ASD. The underlying mechanism of the aberrant expression of GABRB3 gene in ASD patients should be investigated in other biological levels.

Although high rate of curcumin consumption has been suggested to decrease the prevalence of Alzheimer’s disease (AD), its administration has no effect on the progression of AD in humans and this has been attributed to its poor bioavailability. Using nanotechnology to break down curcumin increases its bioavailability and improves its effect on the brain. BSA, as a non-toxic protein with high binding capacity, was used to break curcumin to nanosize and to explore the effect of nanocurcumin on passive avoidance memory and hippocampal MMP-2 and -9 and MAPKs. BSA-based nanocurcumin was produced by desolvation method. In this study, 15 and 20 mg/kg/p.o. nanocurcumin (based on our preliminary studies) were administered to male NMRI mice weighing 20–25 g for 10 days. Passive avoidance training was performed on day 10 and 24 h after, a retention trial was done. Upon completion of behavioral studies, the hippocampi were isolated and western blot analysis was performed on MMP-2, MMP-9, and MAPKs (JNK, ERK, and p38). The results showed that BSA-based nanocurcumin administered at 15 and 20 mg/kg doses resulted in a significantly improved performance in passive avoidance memory test while its equivalent doses of natural curcumin did not produce a similar effect. In addition, this effect was accompanied with an increase in MMP-2, MMP-9, and p-ERK and a decrease in p-JNK. This study indicates that breaking curcumin to nanosize produces improved effects on passive avoidance memory in adult mice accompanied with MMP-2, MMP-9, p-ERK, and p-JNK changes in the hippocampus.

N-acetyl-L-aspartate (NAA), an abundant amino acid present in the vertebrate brain, is synthesized and stored primarily in neurons. Its metabolism is also dynamic, with NAA turning over more than once each day by its regulated efflux into extracellular fluid (ECF), cycling between an anabolic L-aspartate acetylating compartment in neurons and a catabolic NAA deacetylating compartment in oligodendrocytes. An inborn error in NAA metabolism results in Canavan disease (CD), a rare and usually fatal early-onset autosomal recessive human central nervous system (CNS) disease, caused by failure of the catabolic metabolism of NAA resulting from a lack of sufficient amidohydrolase II activity in oligodendrocytes. Various hypotheses regarding the metabolism of NAA and its role have been considered, and although NAA may perform several functions in the CNS, an important role of NAA appears to be osmoregulatory. Based on this role, an osmotic-hydrostatic mechanism for the etiology of the CD phenotype is proposed. In CD, the daily addition of 13375 Pascals (0.132 atmospheres or 1.94 lbs per square inch) of hydrostatic pressure to brain ECF, on the brain cell side of brain-barrier epithelial membranes, resulting from the continuous synthesis and efflux of NAA, is considered to be responsible for the syndrome.

Oxidative stress has been reported in Wilson’s disease with neurological manifestation (WDNM), but there is a paucity of studies on the role of adjunctive antioxidant therapy. This study aims to evaluate the efficacy of adjunctive vitamin C and E treatment in reducing oxidative stress and improving clinical outcomes. Forty-nine patients with WDNM were included and their clinical details were noted. Glutathione (GSH), total antioxidant capacity (TAC), and malondialdehyde (MDA) were measured using spectrophotometer at baseline and follow-up. All patients received zinc with or without chelating therapy, and 32 of them prescribed vitamin C (500 mg/day) and E (400 mg/day). Clinical outcomes at 6, 12, and 24 months were categorized as improved, static, or worsened based on improvement in Burke-Fahn-Marsden (BFM) score (>10%) and/or severity grade (> 1). Baseline parameters were similar between two groups; except BFM score was higher in the antioxidant group. At follow-up, the antioxidant group had higher GSH, TAC, and lower MDA levels compared with baseline. Patients on antioxidant treatment experienced improvement more frequently at 6 (53.1% vs. 29.4%), 12 (62.5% vs. 29.4%), and 24 months (68.8% vs. 35.3%) compared with those without antioxidant treatment. In WDNM, adjunctive vitamin C and E treatment reduce oxidative stress and improve clinical outcome.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that was first isolated from the ovine hypothalamus. PACAP has previously been shown in in vitro experiments to have neuroprotective effects, but its possible application in clinical situations must first be tested in vivo. We examined the protective effect of PACAP against retinal ganglion cell (RGC) death following optic nerve transection in the rat. Fourteen days after sectioning of the optic nerve, the number of RGCs in the vehicle control (untreated: vehicle 0.9% saline, volume 3 μl, injected into the vitreous body) group with axotomized optic nerve was decreased compared with that of intact animals. The number of RGCs in PACAP-treated animals (10 or 100 pM dose added to the vehicle) was significantly increased compared with the vehicle control group. These results indicate that PACAP suppresses ganglion cell death induced by optic nerve transection.