Bahram Soltani Tehrani

Transplanted Bone Marrow Mesenchymal Stem Cells Improve Memory in Rat Models of Alzheimer's Disease

The present study aims to evaluate the effect of bone marrow mesenchymal stem cells (MSCs) grafts on cognition deficit in chemically and age-induced Alzheimers models of rats. In the first experiments aged animals (30 months) were tested in Morris water maze (MWM) and divided into two groups: impaired memory and unimpaired memory. Impaired groups were divided into two groups and cannulated bilaterally at the CA1 of the hippocampus for delivery of mesenchymal stem cells (500 × 103/μL) and PBS (phosphate buffer saline). In the second experiment, Ibotenic acid (Ibo) was injected bilaterally into the nucleus basalis magnocellularis (NBM) of young rats (3 months) and animals were tested in MWM. Then, animals with memory impairment received the following treatments: MSCs (500 × 103/μL) and PBS. Two months after the treatments, cognitive recovery was assessed by MWM in relearning paradigm in both experiments. Results showed that MSCs treatment significantly increased learning ability and memory in both age- and Ibo-induced memory impairment. Adult bone marrow mesenchymal stem cells show promise in treating cognitive decline associated with aging and NBM lesions.

Generation and characterization of nanobodies targeting PSMA for molecular imaging of prostate cancer

Nanobodies show attractive characteristics for tumor targeting in cancer diagnosis and therapy. A radiolabeled nanobody binding the prostate-specific membrane antigen (PSMA) could offer a noninvasive strategy to select prostate cancer patients eligible for PSMA-targeted therapies. We here describe the generation, production and in vivo evaluation of anti-PSMA nanobodies. Nanobodies were derived from heavy-chain-only antibodies, raised in immunized dromedaries. Binding characteristics were evaluated through ELISA and flow cytometry. Selected nanobodies were radiolabeled with (99m) Tc at their hexahistidine tail, after which cell binding capacity and internalization were evaluated on PSMA(pos) LNCaP and PSMA(neg) PC3 cell lines. In vivo tumor targeting was analyzed in both LNCaP and PC3 xenografted mice through SPECT/microCT and tissue sampling. A panel of 72 generated clones scored positive on ELISA, all contributing to three nanobody groups, of which group 3 dominated with 70 clones. ELISA and FACS analysis led to the selection of two dominant nanobodies. (99m) Tc-labeled PSMA6 and PSMA30 both showed specific binding on LNCAP cells, but not on PC3 cells. (99m) Tc-PSMA30 internalized significantly more in LNCaP cells compared to (99m) Tc-PSMA6. Higher absolute tumor uptake and tumor-to-normal organ ratios were observed for (99m) Tc-PSMA30 compared with (99m) Tc-PSMA6 and a (99m) Tc-control nanobody in LNCaP but not in PC3 tumor-bearing mice. PSMA30 nanobody has improved targeting characteristics both in vitro as well as in vivo compared with PSMA6 and the control nanobody, and was therefore selected as our in-house-developed lead compound for PSMA targeting.

Long term habitual exercise is associated with lower resting level of serum BDNF

This experiment has been designed to evaluate the basal serum BDNF level and memory performance, and also the change in BDNF in response to acute aerobic and anaerobic training in athletes and sedentary groups. Nineteen middle aged elite athletes (45-65 years) who used to be competing at domestic championship for more than 10 years and 20 sedentary subjects participated in this study. Blood samples and cognitive function were assessed at rest and also after performing a single bout of acute aerobic and anaerobic exercise. Basal serum BDNF significantly was lower in the athletes group compared to the control one (475.18±45.32, 1089.30±94.92, P=0.001). Serum BDNF was inversely correlated with Vo2 max (r=-0.5, P=0.013), but positively with BMI (r=0.2, p=0.4). Pictures recall memory was better in the athlete group (9.25±1.61) compared with the control ones (8±1.15, p=0.04). Basal platelets did not show any significant differences between athletes and controls (p>0.05). Both acute aerobic and anaerobic activity elevated serum BDNF and platelets in athletes and sedentary groups compared with rest (P<0.001). This study suggests that long-term habitual exercise is associated with lower peripheral BDNF and better intermediate memory. However acute form of intensive activity either aerobic or anaerobic are capable to elevate serum BDNF level in both sedentary and athletes.

Influence of aerobic training and detraining on serum BDNF, insulin resistance, and metabolic risk factors in middle-aged men diagnosed with metabolic syndrome.

Objective:To study the influence of aerobic exercise training on brain-derived neurotrophic factor (BDNF), insulin resistance, and lipid profile in middle-aged men diagnosed with metabolic syndrome (MetS). Design:This is an experimental repeated measure study. Setting:Subjects participated in aerobic training programs (18 sessions of 25-40 minutes per session) in Guilan University gymnasium and court. Participants:A total of 21 middle-aged men (50-65 years old) diagnosed with MetS participated. Interventions:We randomly divided 21 middle-aged men with MetS into exercise and control groups. The exercise group followed an aerobic training program (18 sessions, 3/wk) at 50% to 60% of peak (25-40 minutes per session) and 6 weeks of detraining. Blood samples were collected at baseline, end of the training, and detraining. Main Outcome Measures:High BDNF level in patients with MetS and its reduction after chronic aerobic exercise. Results:Aerobic training significantly decreased all the metabolic risk factors, including overall MetS z score, insulin resistance, and lipid profile (P < 0.05). After the detraining period, plasma triglyceride, high-density lipoprotein, and also overall MetS z score remained unchanged (P < 0.05); however, serum BDNF, which was decreased by aerobic training (P = 0.013), restored to the baseline at the end of the detraining (P = 0.018). Conclusions:Improved metabolic risk factors along with decreased serum BDNF in response to aerobic training and the opposite direction during the detraining emphasize the importance of physical activity in the treatment of MetS and prevention of related diseases.

Camel Heavy Chain Antibodies Against Prostate-Specific Membrane Antigen

Prostate-specific membrane antigen (PSMA), a type II integral membrane glycoprotein, is highly overexpressed in all forms of prostate cancer tissues. It has also been demonstrated in a wide range of neovasculature of non-prostatic solid tumors, including bladder, pancreas, lung, kidney, colorectal, and gastric cancers. Given the unique expression of PSMA, it is considered an alluring target for antibody-based imaging and therapy of cancer. In the present study, the production and characterization of camel heavy chain antibodies (HCAbs) specific for the external domain of the PSMA are reported. Due to the absence of the CH1 domain, HCAbs are smaller than their counterparts in conventional antibodies. In this study, camel antibodies were generated through immunization of Camelus dromedarius with a synthetic 28 amino acid peptide corresponding to the external surface domain of antigen and PSMA-expressing cell lines. Different binding properties to protein A and protein G affinity columns were deployed to separate three subclasses of camel IgG. The affinity purified HCAbs bound selectively to the synthetic peptide in enzyme linked immunosorbent assay (ELISA) and reacted specifically with PSMA-expressing cell line through immunocytochemistry study. Currently, we are attempting to develop recombinant variable domain of these heavy chain antibodies (VHH or nanobody) for tumor imaging and cancer therapy.

The Effect of Estrogen Replacement Therapy on Visceral Fat, Serum Glucose, Lipid Profiles and Apelin Level in Ovariectomized Rats

Objectives Ovarian hormones have been shown to regulate body weight, intra-abdominal fat accumulation and plasma level of cytokines. The aim of this study was to investigate the effect of estrogen replacement therapy on visceral adipose tissue, plasma level of apelin, lipid profiles, and glucose in ovariectomized (OVX) rats. Methods Thirty female Wistar rats were divided into OVX (n = 20) and sham (n = 10) groups. OVX rats were subdivided into estrogen replacement therapy (OVX+est; n = 10) receiving 17 β-estradiol valerates (30 µg/kg, s.c., 5 day/week, for eight weeks), and vehicle control group receiving sesame oil same as experiment group (OVX+ses oil; n = 10). After the treatments, all groups were sacrificed and blood samples were collected, visceral fats were taken from the abdominal cavity and weighed immediately. Apelin were measured using enzyme-linked immunosorbent assay kits. Lipid profiles and glucose were measured using the enzymatic colorimetric method. Data were analyzed with one-way analysis of variance and (P < 0.05) determined as the statistical significance level. Results After eight weeks, body weight, body mass index (BMI), visceral fat, apelin and lipid profiles (P < 0.01) were increased significantly in OVX rats compared to sham group. Treatment with estrogen leads to significant reduction in body weight and BMI (P < 0.05), there was no significant change in serum apelin level in OVX+est rats compared to OVX+ses. Conclusions These results suggest that estradiol replacement therapy successfully attenuated some of the metabolic syndrome components, and apelin does not probably stand as a mediator of these physiological functions.