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BACKGROUND: Obesity has a strong association with the risk of developing cognitive impairment and dementia at a later age. Brain-derived neurotrophic factor (BDNF) and its receptor appear to be important components in cognitive function and are also involved in energy homeostasis. The level of circulating BDNF and its association with cognition has yet to be delineated clearly. In this work we studied the association of circulating BDNF with cognition among the adult obese population. METHODS: The study involved 132 healthy participants between 18 and 40 years of age and of both sexes. The participants were categorized into an obesity group (n=66) and a non-obese group (n=66) based on their body mass index (Asian criteria). The level of cognitive performance was assessed by the event-related potentials P300 (ERPs-P300), mini-mental state examination (MMSE), both visual and auditory reaction times (VRT and ART, respectively), and other pen and paper tests related to memory and executive function. Serum BDNF, glycemic and lipid profiles were estimated. RESULTS: We found significant differences in the ERPs-P300 latency (P<0.001) and amplitude (P=0.002) between the non-obese and obese group. The MMSE score was significantly reduced while VRT (P=0.005) and ART (P=0.001) were larger in the obese group. BDNF levels (P<0.001) were significantly reduced and negatively associated with the obese group. ERPs-P300 latency was negatively associated (r=-0.674, P=0.001) whereas amplitude (r=0.507, P<0.001) was positively associated with the BDNF levels in the adult obese population. CONCLUSION: We found reduced circulating BDNF levels in obese adults and that lower BDNF levels were strongly associated with cognitive decline in the obese adult population.

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This study examined the effects of systemic administration of the TrkB receptor antagonist (ANA-12) during induction of morphine dependence on the severity of physical and psychological dependence and the cerebrospinal fluid (CSF) BDNF levels in morphine-dependent and withdrawn rats. Rats became morphine-dependent by increasing daily doses of morphine for 7 days, along with ANA-12 injection. Then, rats were tested for the severity of physical dependence on morphine (spontaneous withdrawal signs), anxiety-like (the elevated plus maze), depressive-like (sucrose preference test) behaviors after spontaneous morphine withdrawal. Also, the CSF BDNF levels were assessed 2 h after the last dose of morphine and day 13 after morphine withdrawal in morphine-dependent and withdrawn rats. We found that the morphine withdrawal signs were significantly higher in morphine dependent rats receiving ANA-12 on days of 5-7 after morphine withdrawal, also ANA-12 exacerbated overall dependence severity. While, the percentage of time spent in the open arms and sucrose preference were higher in morphine-dependent rats receiving ANA-12 than morphine-dependent rats receiving saline. Also, the ANA-12 injection decreased the CSF BDNF levels following morphine dependence, while increased it after morphine withdrawal. We conclude that the ANA-12 exacerbated the severity of physical morphine dependence but attenuated the anxiety/depressive-like behaviors in morphine-dependent and withdrawn rats. Also, ANA-12 injection was able to reverse the changes in the CSF BDNF levels. Therefore, ANA-12 is not more likely to complete treatment for opiate addiction.

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This study examined the effects of systemic administration of the TrkB receptor antagonist (ANA-12) on the severity of physical and psychological dependence and morphine-induced locomotor sensitization, the ventral tegmental area (VTA)-nucleus accumbens (NAc) BDNF levels in morphine-dependent and withdrawn rats. Rats were injected with bi-daily doses (10 mg/kg, at 12 h intervals) of morphine for 10 days. Then, rats were tested for naloxone-precipitated morphine withdrawal signs, the anxiety (the elevated plus maze-EPM) after the last morphine injection and injection of ANA12 (ip). Also, morphine-induced locomotor sensitization was evaluated after morphine challenge followed by an injection of ANA-12 in morphine-withdrawn rats. The VTA-NAc BDNF levels were assessed in morphine-dependent and withdrawn rats. The overall Gellert-Holtzman score was significantly higher in morphine-dependent rats receiving ANA-12 than in those receiving saline. Also, the percentage of time spent in the open arms in control and morphine-dependent rats receiving ANA-12 were higher compared to the Cont/Sal and D/Sal rats, respectively. There was no significant difference in the locomotor activity and the VTA-NAc BDNF levels between D/Sal/morphine and D/ANA-12/morphine groups after morphine withdrawal. We conclude that the systemic administration of ANA-12 exacerbates the severity of physical dependence on morphine and partially attenuates the anxiety-like behavior in morphine-dependent rats. However, ANA-12 did not affect morphine-induced locomotor sensitization and the VTA-NAc BDNF levels in morphine-dependent and withdrawn rats.

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The function and morphology of ß-cells is largely dependent on insulin demand. As ß-cells cover a bigger cell proportion in pancreas islets, changes of insulin producer cells affect the whole pancreatic islet morphology. Growth factors as the neurotrophins regulate the pancreas physiology, besides; physical exercise increases insulin sensitivity, and further modifies brain derived neurotrophic factor (BDNF) concentration in plasma. The aim of this study was to investigate the effects of chronic exercise (running in a treadmill for 8 weeks) intensity on pancreatic islet morphometry in healthy state. The BDNF receptor effect on the pancreatic islet morphometry was also evaluated. Adult male Wistar rats were divided in 6 groups: Control (C); moderate intensity training (MIT); high intensity training (HIT) did not treat with BDNF receptor inhibitor (K252a), and C, MIT and HIT treated with K252a. The results shown that chronic exercise induces ß-cells hypertrophy without BDNF receptor participation. On the other hand, the moderate exercise increases the number of ß cells per islet; the last effect does not require TrkB participation. In sedentary conditions, the K252a treatment reduced the ß-cell density. Exercise intensity has differential effects on pancreas islet morphometry in healthy model; furthermore, BDNF receptor plays a role to maintain the amount of ß-cells in sedentary state.

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Chronic restraint stress leads to increases in brain derived neurotrophic factor (BDNF) mRNA and protein in some regions of the brain, e.g. the basal lateral amygdala (BLA) but decreases in other regions such as the CA3 region of the hippocampus and dendritic spine density increases or decreases in line with these changes in BDNF. Given the powerful influence that BDNF has on dendritic spine growth, these observations suggest that the fundamental reason for the direction and extent of changes in dendritic spine density in a particular region of the brain under stress is due to the changes in BDNF there. The most likely cause of these changes is provided by the stress initiated release of steroids, which readily enter neurons and alter gene expression, for example that of BDNF. Of particular interest is how glucocorticoids and mineralocorticoids tend to have opposite effects on BDNF gene expression offering the possibility that differences in the distribution of their receptors and of their downstream effects might provide a basis for the differential transcription of the BDNF genes. Alternatively, differences in the extent of methylation and acetylation in the epigenetic control of BDNF transcription are possible in different parts of the brain following stress. Although present evidence points to changes in BDNF transcription being the major causal agent for the changes in spine density in different parts of the brain following stress, steroids have significant effects on downstream pathways from the TrkB receptor once it is acted upon by BDNF, including those that modulate the density of dendritic spines. Finally, although glucocorticoids play a canonical role in determining BDNF modulation of dendritic spines, recent studies have shown a role for corticotrophin releasing factor (CRF) in this regard. There is considerable improvement in the extent of changes in spine size and density in rodents with forebrain specific knockout of CRF receptor 1 (CRFR1) even when the glucocorticoid pathways are left intact. It seems then that CRF does have a role to play in determining BDNF control of dendritic spines.

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