Serum BDNF Levels Research Articles

Differential effects of chronic and intermittent administration of taurine on alcohol binge drinking in male rats

Episodic consumption of high doses of alcohol in a short period (binge drinking - BD) among adolescents is known to be harmful to their brain development. Chronic use of taurine increases voluntary alcohol consumption and shows an anxiolytic-like effect in rats. In this study, we evaluated the differential effects of chronic and intermittent taurine administration on alcohol consumption and behavioral changes in adolescent and young adult rats subjected to the BD model. Male Wistar rats (35 days old) were divided into 4 groups for daily intraperitoneal administration of saline (SAL); taurine, 100 mg/kg (TAU); taurine on BD days and saline on intervals (TAU/SAL); and saline on BD days and taurine on intervals (SAL/TAU). They were exposed to 4 cycles of BD, with free access to alcoholic solution (20 % w/v), for 2 h, 3 days per week. At the end of the 3rd cycle, anxiety-like behaviors were assessed using the light-dark task. After euthanasia, plasma and prefrontal cortex samples were collected to measure corticosterone and BDNF levels, respectively. Chronic taurine treatment did not alter alcohol consumption in rats, whereas intermittent administration increased alcohol intake after 4 BD exposures (TAU/SAL: +19.4 % and SAL/TAU: +21.6 %). No anxiolytic-like effects were found by taurine administration, nor were there changes in serum corticosterone or BDNF levels in the frontal cortex of young adult rats. Intermittent taurine, but not chronic treatment, increased alcohol intake among rats after the second week of exposure. The translation of these results to humans is concerning since the combination of alcohol and drinks containing taurine is common among adolescent and young adult individuals.

Longitudinal associations between early post-injury serum BDNF levels and the development of post-traumatic stress disorder over two years

BackgroundThis study investigated the longitudinal associations between serum BDNF (sBDNF) levels measured early after injury and the onset of post-traumatic stress disorder (PTSD) across two years. MethodsPatients with moderate to severe physical injuries were enrolled from a trauma center. At baseline, sBDNF levels were measured and a comprehensive socio-demographic and clinical data were collected. The range of time from physical injuries to blood collection was 1–28 days, with a median (IQR) of 8.0 (6.0) days. PTSD diagnoses were determined at 3, 6, 12, and 24 months post-injury using the CAPS-5. Linear regression analyses assessed the relationship between sBDNF levels and PTSD diagnoses. ResultsOut of 923 patients, 112 (12.1 %) developed PTSD during the study. Prevalence rates were 8.8 % at 3 months, 7.6 % at 6 months, 4.8 % at 12 months, and 3.7 % at 24 months. Significantly, lower sBDNF levels were associated with PTSD at 12 and 24 months, after adjusting for covariates and applying Bonferroni corrections, but not at earlier assessments. LimitationsFocusing on patients with moderate to severe injuries from a single center may limit the findings' generalizability. ConclusionEarly post-injury sBDNF levels are predictive biomarkers for PTSD, especially significant at 12 and 24 months post-injury.

The Effect of a Single About of Resistance Exercise with Two Intensities and Different Recovery on Pro-Inflammatory Factor TNF-Α, HSP-70, And Anti-Inflammatory Factor BDNF In Female Bodybuilders

Background and purpose: resistance exercises with high loads of HLRT can cause physiological changes, including in the immune system. The purpose and credibility of qualitative research investigated the effect of a resistance activity session with two different intensities and recovery on the expression of TNF-α, HSP-70, and BDNF genes in female bodybuilders.Methods: In this Quasi-experimental study, twelve healthy female bodybuilders (age 30±5) volunteered to participate in the research. The samples performed one weekly strength training protocol session designed at two intensities of one maximum repetition in two different recovery times of one and two minutes. 36 hours after the end of the training, sampling was done after ten hours of fasting, and the samples were centrifuged and stored at minus 20℃. At the end of the four stages, the levels of TNF-α, HSP-70, and BDNF were checked in the medical laboratory. A consent form was obtained from all the participants. SPSS version 27 software was used for data analysis at a significance level of α ≤ 0.05.Findings: The results showed that HLRT resistance training compared to moderate intensity resistance training, by increasing the training intensity to 85% of a maximum repetition and recovery time of one and two minutes, significantly reduced TNF-α level (with p<0.001and a significant increase in the serum levels of BDNF and HSP-70 (with p<0.0001).Conclusion: It seems that increasing the intensity of HLRT resistance training has no negative effect on the immune system, and probably with the decrease of the pro-inflammatory factor TNF-α and HSP-70, the anti-inflammatory factor BDNF also increased reduces the incidence of inflammation in female bodybuilders.

Exploring the Influence of IL-8, IL-10, Patient-Reported Pain, and Physical Activity on Endometriosis Severity.

Endometriosis is known to be a chronic, debilitating disease. The pathophysiological mechanisms of endometriosis development include local chronic inflammation and a certain degree of local immune deficit. We investigated the relationship between the endometriosis severity, IL-8, IL-10, BDNF, VEGF-A serum and tissue levels, patient-related pain, and physical activity in a cohort of 46 patients diagnosed with endometriosis who underwent surgery. The same panel of biomarkers was investigated in a control group of 44 reproductive-aged patients with non-endometriotic gynecological pathology who underwent surgical intervention. Our data show a high statistical significance between tissue expression of IL-8, IL-10, patient-related pain, and the severity of endometriosis. No relationship was identified between serum or tissue levels of VEGF-A and BDNF and the severity of endometriosis. These results validate the presence of local chronic inflammation and immune deficit, thereby creating, alongside other studies in the field, an opportunity for the development of innovative and personalized treatment approaches in endometriosis.

The Association Between Serum Mature and Precursor Brain-Derived Neurotrophic Factor and Neurocognitive Function in People With Human Immunodeficiency Virus: A Longitudinal Study.

Despite antiretroviral therapy (ART), human immunodeficiency virus (HIV)-associated neurocognitive impairment persists. We investigated the association between serum levels of mature brain-derived neurotrophic factor (mBDNF), precursor brain-derived neurotrophic factor (proBDNF), and neurocognitive changes over time among adults with HIV in sub-Saharan Africa, seeking to elucidate the interplay between neurotrophic factors and neurocognitive outcomes post-ART. Utilizing data from the ACTG 5199 study in Johannesburg and Harare, serum mBDNF and proBDNF levels were measured via enzyme-linked immunosorbent assay. Neurocognitive performance was assessed at baseline and 24, 48, and 96 weeks using neuropsychological tests. The Friedman test and linear mixed-effects models were used to assess changes in mBDNF, proBDNF, and neurocognitive performance over time, accounting for individual variability and adjusting for multiple comparisons. Among 155 participants, there were significant cognitive improvements (P < .001) and a rise in mBDNF levels from baseline to 96 weeks. The proBDNF levels initially remained stable (P = .57) but notably increased by 48 weeks (P = .04). Higher mBDNF levels were positively associated with enhanced neurocognitive performance at 48 weeks (β = .16, P = .01) and 96 weeks (β = .32, P < .001). Similarly, higher proBDNF levels were positively associated with neurocognitive performance at 96 weeks (β = .25, P < .001). This study highlights the significant association between serum BDNF levels and neurocognitive improvement post-ART in adults with HIV. However, more research is needed to replicate these findings, establish causal relationships, and explore whether BDNF-enhancing activities can improve neurocognitive outcomes in people with HIV.

Delayed effects of alcohol consumption on the association between serum BDNF levels and post-traumatic stress disorder development over two-years

BackgroundsThis study aimed to examine the individual and combined effects of serum BDNF (sBDNF) levels and alcohol consumption status, assessed shortly after a physical injury, on the development of post-traumatic stress disorder (PTSD) over two years. MethodsParticipants were consecutively recruited from a trauma center and followed prospectively for two years. At baseline, sBDNF levels and alcohol consumption history were assessed. A range of socio-demographic and clinical covariates were also collected. PTSD diagnosis during follow-up (3, 6, 12, and 24 months post-injury) was established using the Clinician-Administered PTSD Scale for DSM-5. Binary and multinomial logistic regression analyses were employed to investigate the relationships between sBDNF levels, alcohol consumption status, and PTSD onset. ResultsOut of 923 participants analyzed, 112 (12.1%) developed PTSD at some point during the study, with prevalence rates of 8.8% at 3 months, 7.6% at 6 months, 4.8% at 12 months, and 3.7% at 24 months. The study found no individual associations between sBDNF levels or alcohol consumption status and PTSD development. However, lower sBDNF levels significantly predicted PTSD in individuals who consumed alcohol, a relationship not observed in non-drinkers, with significant interaction terms. This pattern was consistent at later follow-up points from 12 to 24 months, but not at earlier assessments at 3 and 6 months. LimitationsThe study's reliance on participants from a single trauma center with moderate to severe injuries may limit the generalizability of the findings. ConclusionsA significant interaction between sBDNF levels and alcohol consumption in relation to PTSD development was observed, particularly in the long term. These findings highlight the necessity of considering both sBDNF levels and alcohol consumption in strategies aimed at preventing PTSD among individuals with physical injuries, underscoring the need for tailored approaches based on these factors.

Antidepressant effects of selective adenosine receptor antagonists targeting the A1 and A2A receptors administered jointly with NMDA receptor ligands: behavioral, biochemical and molecular investigations in mice

BackgroundThe objective of the study was to ascertain the antidepressant potential of the co-administration of NMDA receptor ligands and selective adenosine A1 and A2A receptor antagonists.MethodsThe forced swim test (FST) and spontaneous locomotor activity test were carried out in adult male naïve mice. Before the behavioral testing, animals received DPCPX (a selective adenosine A1 receptor antagonist, 1 mg/kg) or istradefylline (a selective adenosine A2A receptor antagonist, 0.5 mg/kg) in combination with L–701,324 (a potent NMDA receptor antagonist, 1 mg/kg), D–cycloserine (a partial agonist at the glycine recognition site of NMDA receptor, 2.5 mg/kg), CGP 37849 (a competitive NMDA receptor antagonist, 0.3 mg/kg) or MK–801 (a non-competitive NMDA receptor antagonist, 0.05 mg/kg). Additionally, serum BDNF level and the mRNA level of the Adora1, Comt, and Slc6a15 genes in the murine prefrontal cortex were determined.ResultsThe obtained results showed that DPCPX and istradefylline administered jointly with NMDA receptor ligands (except for DPCPX + D–cycloserine combination) produced an antidepressant effect in the FST in mice without enhancement in spontaneous motility of animals. An elevation in BDNF concentration was noted in the D–cycloserine-treated group. Adora1 expression increased with L–701,324, DPCPX + D–cycloserine, and DPCPX + CGP 37849, while D–cycloserine, CGP 37849, and MK–801 led to a decrease. Comt mRNA levels dropped with DPCPX + L–701,324, istradefylline + L–701,324/CGP 37849 but increased with D–cycloserine, MK–801, CGP 37849 and DPCPX + MK–801/ CGP 37849. Slc6a15 levels were reduced by D–cycloserine, DPCPX + L–701,324 but rose with DPCPX + CGP 37849/MK–801 and istradefylline + D–cycloserine/MK–801/CGP 37849.ConclusionOur study suggests that selective antagonists of adenosine receptors may enhance the antidepressant efficacy of NMDA receptor ligands highlighting a potential synergistic interaction between the adenosinergic and glutamatergic systems. Wherein, A2A receptor antagonists are seen as more promising candidates in this context. Given the intricate nature of changes in BDNF levels and the expression of Adora1, Comt, and Slc6a15 seen after drug combinations exerting antidepressant properties, further research and integrative approaches are crucial understand better the mechanisms underlying their antidepressant action.

Impact of social isolation on corticosterone release and recovery after stroke in aged rats: A behavioral and biochemical analysis

Social isolation (SI) after stroke reduces recovery. The aim of this study was to evaluate the effects of SI on corticosterone release and recovery after stroke in aged rats. A total of 64 male Wistar rats (aged 24 months) were used in the present study. All rats were housed in pairs for two weeks. After two weeks, rats were randomly assigned to one of four groups: (1) rats underwent sham surgery and kept socially isolated (control/social isolated (CO/SI) group); (2) rats underwent sham surgery and kept pair housed (control/pair housed (CO/PH) group); (3) rats underwent middle cerebral artery occlusion (MCAO) surgery and kept socially isolated (stroke/isolated (ST/SI) group); (4) rats underwent MCAO surgery and kept pair housed (stroke/pair housed (ST/PH)) group. Behaviors were assessed using the adhesive removal test, rotarod test and social interaction test at 1st, 7th, 14th and 21st days after stroke. Serum biochemical analysis was also performed on the behavioral testing days. Results showed THAT serum corticosterone and MDA levels in CO/PH group were significantly lower than CO/SI group. Serum BDNF levels in CO/PH group was significantly higher than CO/SI group. Serum corticosterone and MDA levels in ST/PH group were lower than ST/SI group. In ST/PH group, serum Total antioxidant capacity (TAC) and BDNF levels were significantly higher than ST/SI group. Biochemical analysis of certain regions of the brain (hippocampus, striatum and cerebral cortex) was performed on 21st day after stroke. In the hippocampus of CO/PH group, BDNF and TAC levels were significantly higher than CO/SI group. The hippocampal MDA level of CO/PH group were significantly lower than CO/SI group. BDNF and TAC levels in the hippocampus, striatum and cerebral cortex of ST/PH group were significantly higher and MDA level was significantly lower as compared with ST/SI group. Both ischemic groups showed sensorimotor recovery over a 21-day period, but recovery of ST/PH group was significantly greater than ST/SI group. Total social interaction time in ST/PH group was significantly longer than ST/SI group. Based on the results of this study, social interaction after stroke enhances histologic and sensorimotor recovery through reduction of HPA activity and corticosterone release, leading to increased TAC and BDNF levels.

Characterization of pain-related behaviors in a rat model of acute-to-chronic low back pain: single vs. multi-level disc injury.

Low back pain is the most common type of chronic pain. We examined pain-related behaviors across 18 weeks in rats that received injury to one or two lumbar intervertebral discs (IVD) to determine if multi-level disc injuries enhance/prolong pain. Twenty-three Sprague-Dawley adult female rats were used: 8 received disc puncture (DP) of one lumbar IVD (L5/6, DP-1); 8 received DP of two lumbar IVDs (L4/5 & L5/6, DP-2); 8 underwent sham surgery. DP-2 rats showed local (low back) sensitivity to pressure at 6- and 12-weeks post-injury, and remote sensitivity to pressure (upper thighs) at 12- and 18-weeks and touch (hind paws) at 6, 12 and 18-weeks. DP-1 rats showed local and remote pressure sensitivity at 12-weeks only (and no tactile sensitivity), relative to Sham DP rats. Both DP groups showed reduced distance traveled during gait testing over multiple weeks, compared to pre-injury; only DP-2 rats showed reduced distance relative to Sham DP rats at 12-weeks. DP-2 rats displayed reduced positive interactions with a novel adult female rat at 3-weeks and hesitation and freezing during gait assays from 6-weeks onwards. At study end (18-weeks), radiological and histological analyses revealed reduced disc height and degeneration of punctured IVDs. Serum BDNF and TNFα levels were higher at 18-weeks in DP-2 rats, relative to Sham DP rats, and levels correlated positively with remote sensitivity in hind paws (tactile) and thighs (pressure). Thus, multi-level disc injuries resulted in earlier, prolonged and greater discomfort locally and remotely, than single-level disc injury. BDNF and TNFα may have contributing roles.

Serum levels of IL-9 and IL-11 serve as predictors for the occurrence of early neurologic deterioration in patients with cerebral infarction

Background and aimEarly neurological deterioration (END) is a common complication of cerebral infarction and a significant contributor to poor prognosis. Our study aimed to investigate the predictive value of interleukin-9 (IL-9) and interleukin-11 (IL-11) in relation to the occurrence of END in patients with cerebral infarction. Materials and methods102 patients with cerebral infarction and 64 healthy controls were collected. Patients were categorized into two groups based on the development of END following admission: the END group (n = 44) and the non-END group (n = 58). Enzyme-linked immunosorbent assay was used to determine the serum levels of IL-9, IL-11, and BDNF. ResultsSerum IL-9 was higher and IL-11 lower in the END group than those in the non-END group (P < 0.01). IL-9 correlated positively with NIHSS score (r = 0.627) and infarction volume (r = 0.686), while IL-11 correlated negatively (r = -0.613, −0.679, respectively). Logistic regression identified age, NIHSS score, and IL-9 as risk factors (P < 0.01), and IL-11 as protective (P < 0.01). Combined IL-9 and IL-11 had an ROC curve area of 0.849. BDNF correlated negatively with IL-9 (r = -0.703) and positively with IL-11 (r = 0.711). ConclusionSerum IL-9 and IL-11 levels can predict the occurrence of END in patient with cerebral infarction and are correlated with serum BDNF levels.

The association between serum BDNF levels, BDNF polymorphisms, and tardive dyskinesia: A review of current evidence

The association between serum BDNF levels, BDNF polymorphisms, and tardive dyskinesia: A review of current evidence

Comparison of Val66met Polymorphism of BDNF gene in patients of bipolar disorder and healthy controls.

IntroductionThe study aims to explore the utility of BDNF Val66Met polymorphism as a potential biomarker in Indian bipolar disorder patients and its correlation with clinical characteristics.ObjectivesGenotyping Val66Met in BDNF geneExploring its association with bipolar disorder (BD).Methods150 consenting BD patients and matched controls were recruited using a case-control study design. BD severity was assessed using Young’s mania rating scale and the Clinical Global Impression - Severity (CGI-S) scale. BDNF Val66Met polymorphism was identified through real-time PCR after DNA extraction. Data was tested for normal distribution. Genotype frequencies between two groups were compared and the Hardy-Weinberg equilibrium assumptions were tested using Chi-Square tests. Clinical-genotypic associations were explored using the Kruskal-Wallis test and confirmed using hierarchical regression.ResultsOur sample had more males (60%) than females (40%) with mean age of 35.05 years. Most patients had established bipolar disorder and were severely ill (CGI: 38.75, YMRS). Val66Met SNP genotype frequency differed significantly between cases and controls. Val66Val genotype and Val allele were higher in cases. Results consistent with Hardy-Weinberg equilibrium.Table 1.Genotype frequencies of BDNF (rs6265) in cases and controlsGENOTYPECCCTTTCASES94(62.6%)47(31.3%)9(6%)CONTROL71(47.3%)69(46%)10(6.6%)CHI-SQUARE- 7.431DF(Degree of freedom) - 2p-value- 0.024Table 2.Dominant genotype frequencies in cases and controlsDOMINANT GENOTYPECCCT+TTCASES94(62.6%)56(37.3%)CONTROLS71(47.3%)79(52.6)CHI-SQUARE-7.125DF(Degree of freedom)-1p-value-0.007Table 3.Allelic frequencies of BDNF (rs6265) in BD cases and healthy controlsALLELIC VARIATIONCTCASES235(78.3%)65(21.6%)CONTROLS211(70.3%)89(29.6%)CHI-SQUARE-5.032DF(Degree of freedom)-1p-value- 0.024ConclusionsOur study found that Val66Val genotype and Val allele were higher in cases and could be a potential biomarker for bipolar disorder (BD), which is consistent with previous research conducted on the European population. However, further investigations are required to gain a more comprehensive understanding of its impact on BD, including its association with serum BDNF levels, treatment outcomes, and a more diverse study population.Disclosure of InterestNone Declared

Transcranial direct current stimulation is more effective than pregabalin in controlling nociceptive and anxiety-like behaviors in a rat fibromyalgia-like model.

Despite the fact that fibromyalgia, a widespread disease of the musculoskeletal system, has no specific treatment, patients have shown improvement after pharmacological intervention. Pregabalin has demonstrated efficacy; however, its adverse effects may reduce treatment adherence. In this context, neuromodulatory techniques such as transcranial direct current stimulation (tDCS) may be employed as a complementary pain-relieving method. Consequently, the purpose of this study was to evaluate the effect of pregabalin and tDCS treatments on the behavioral and biomarker parameters of rats submitted to a fibromyalgia-like model. Forty adult male Wistar rats were divided into two groups: control and reserpine. Five days after the end of the administration of reserpine (1 mg/kg/3 days) to induce a fibromyalgia-like model, rats were randomly assigned to receive either vehicle or pregabalin (30 mg/kg) along with sham or active- tDCS treatments. The evaluated behavioral parameters included mechanical allodynia by von Frey test and anxiety-like behaviors by elevated plus-maze test (time spent in opened and closed arms, number of entries in opened and closed arms, protected head-dipping, unprotected head-dipping [NPHD], grooming, rearing, fecal boluses). The biomarker analysis (brain-derived neurotrophic factor [BDNF] and tumor necrosis factor-α [TNF-α]) was performed in brainstem and cerebral cortex and in serum. tDCS reversed the reduction in the mechanical nociceptive threshold and the decrease in the serum BDNF levels induced by the model of fibromyalgia; however, there was no effect of pregabalin in the mechanical threshold. There were no effects of pregabalin or tDCS found in TNF-α levels. The pain model induced an increase in grooming time and a decrease in NPHD and rearing; while tDCS reversed the increase in grooming, pregabalin reversed the decrease in NPHD. tDCS was more effective than pregabalin in controlling nociception and anxiety-like behavior in a rat model-like fibromyalgia. Considering the translational aspect, our findings suggest that tDCS could be a potential non-pharmacological treatment for fibromyalgia.

The effect of high-intensity intermittent and moderate-intensity continuous exercises on neurobiological markers and cognitive performance

BackgroundThe effects of exercise on cognitive functions and general brain health have been increasingly studied. Such studies conducted among athletes are very important to understanding the effects of different exercise methods on biochemical parameters and cognitive performance. The present study aimed to compare the neuroprotective effects of high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE) based on biochemical parameters and cognitive performance in athletes.MethodsA total of twenty-eight elite male boxing athletes aged > 18 years, with at least eight years of training experience, who successfully achieved national and international levels were included in this study. The elite athletes participating in the study were aged 24.43 ± 4.72 years, 14.45 ± 5.89 years of training experience, had a body weight of 74.64 ± 7.82 kg, and had a height of 177 ± 7.15 cm. Athletes who consumed any stimulants during the testing or supplementation phase, nutritional supplements, or steroids that may have affected hormone levels or sports performance in the last three months were excluded from this study. Venous blood samples were obtained, and cognitive performance tests (Stroop tests) were applied (i) immediately after high-intensity intermittent exercise (HIIE), (ii) one hour after HIIE, (iii) immediately after moderate-intensity continuous exercise (MICE), and (iv) one hour after MICE. Serum BDNF, S100B, and NSE levels were measured after each session.ResultsSerum BDNF levels were significantly (F = 2.142, P < 0.001, ηp2 = 0.589) greater in the HIIE group (5.65 ± 1.79 ng/mL) than in the control group (1.24 ± 0.54 ng/mL) and MICE group (3.38 ± 1.29 ng/mL) for the samples obtained immediately after exercise. Serum S100B levels were significantly (F = 3.427, P < 0.001, ηp2 = 0.427) greater in the HIIE group (71.92 ± 23.05 ng/L) than in the control group (47.39 ± 15.78 ng/L), however there was no significant difference between the HIIE and MICE groups (59.62 ± 28.90 ng/L) in the samples obtained immediately after exercise. Serum NSE levels were significantly (F = 1.475, P < 0.001, ηp2 = 0.312) greater in the HIIE group (14.57 ± 2.52 ng/mL) than in the control group (9.51 ± 3.44 ng/ML mL), however there was no significant difference between the HIIE and MICE groups (59.62 ± 28.90 ng/L) in the samples obtained immediately after exercise. Compared with control groups, both HIIE and MICE improved cognitive performance demonstrated by the Stroop test results. Again, HIIE was superior to MICE in terms of Stroop task reaction time and error rate (incongruent task) scores.ConclusionHIIE and MICE have favorable effects on improving cognitive performance and neuroprotection in an athlete population. HIIE is considered to be superior to MICE in improving neuroprotection and cognitive performance. Our study has remarkable results demonstrating the benefits of HIIT on neuroprotection and cognitive performance. HIIE is recommended instead of MICE, especially in sports where cognitive performance is more important.

Gestational environmental enrichment prevents chronic social stress induced anxiety- and ethanol-related behaviors in offspring

Epidemiological surveys have shown a strong relationship between maternal stress and offspring's mood disorders. Growing evidence suggested that environmental enrichment (EE) improves cognitive function in models of psychiatric and neurological disorders. However, the potential protective effects of gestational EE on social stress-elicited mood disorders in offspring have not been studied. Knowing that the undeveloped brain is more sensitive to gestational environmental stimuli, we hypothesized that initiating cognitive stimulation, during gestation, would protect against social stress-induced behavioral alterations in adulthood. Therefore, the present study aimed to investigate the effects of gestational EE on social stress-elicited anxiety- and ethanol-related behaviors in adult offspring. EE consisted of free access, of dams, to tubular devices of different shapes, colors, and sizes that were changed regularly. After birth and weaning, young adult offspring were exposed to 19 days of social stress and anxiety-like behavior was evaluated by elevated plus maze, open field, and marbles burying tests. The two-bottle choice (TBC) drinking paradigm was used to assess stress-induced ethanol intake. Results showed that gestational EE prevented social stress-elicited anxiogenic-like effects with no differences in spontaneous locomotor activity. Moreover, in the TBC paradigm, mice pre-exposed to EE consistently showed a significantly decreased consumption and preference for ethanol with no effects on tastants' intakes. Interestingly, gestational EE increased serum BDNF levels, which showed a correlation with measures of anxiety- and ethanol-related behaviors. These findings indicate that some neurodevelopmental changes associated with prenatal EE may counteract adult social stress-induced behavioral alterations through a BDNF mechanism. Therefore, we propose that gestational EE has significant protective and beneficial effects on social stress-induced cognitive impairment. It can also alleviate anxiety-like behavior and subsequent excessive alcohol consumption.

Cognitive Dysfunction and Affective Mood Disorder Screening in Patients With Chronic Inflammatory Bowel Disease: Protocol for a Prospective Case-Control Study.

Mild cognitive impairment (MCI) and Alzheimer's disease (AD) might be more frequent in patients with inflammatory bowel disease (IBD), but the relationship between these 2 entities is yet to be entirely established. Certain blood biomarkers (eg, serum amyloid A [SAA] and serum homocysteine [Hcy], which increase in IBD and MCI; brain-derived neurotrophic factor [BDNF], which decreases in MCI and AD but is not clearly modified in IBD; and S100 calcium-binding protein B [S100B], which increases in the blood-brain barrier and neuronal lesions) might predict the stage of MCI or dementia or progression to a further state. The gut-brain axis (GBA) might be the key to the development of MCI in patients with IBD, along with systemic inflammation and the possible and unknown adverse effects of disease-modifying medication. The aim of this study is to investigate whether GBA interactions play a role in MCI development in patients with IBD. A case-control study will be conducted on at least 100 patients diagnosed with IBD, matched with 100 healthy individual controls. The matching will include sex, age, and education. Patients will be fully examined, and a full interview and a neurological and cognitive examination will be performed. The primary clinical outcomes will be cognitive test scores (Montreal Cognitive Assessment, Trail Making Test, Digit Symbol Substitution Test, forward and backward digit span testing). Depression, stress, and anxiety screening will also be performed. Blood samples from all participants will be collected, and aliquots will be immediately stored in a biobank. Primary laboratory outcomes will include serum levels of presumed cognitive dysfunction blood biomarkers SAA, Hcy, S100B, and BDNF. Follow-up will be performed at 12, 24, 36, and 48 months. Data collection started in December 2021 and is ongoing. So far, 53 patients with IBD have been recruited and 50 HC matched. Data collection should end in January 2030. Intermediary analysis will be performed in April 2024. We expect patients with IBD to have lower scores on cognitive testing and a positive correlation between disease length and cognitive impairment level. In addition, the levels of stress, anxiety, and depression should be higher in the IBD group. The serum levels of the 4 biomarkers could correlate or anticorrelate with cognitive scores and serve as predictive factors for MCI or dementia development. A higher level of education, a younger age, the absence of malabsorption, and good disease control might serve as protectors against MCI. GBA interactions, along with systemic inflammation and the adverse effects of medication, might be a cause of MCI and AD development in patients with IBD. Serum biomarkers could prove cheap and useful predictors of MCI development. ClinicalTrials.gov NCT05760729; https://clinicaltrials.gov/study/NCT05760729. DERR1-10.2196/50546.

The effect of subthreshold depressive symptoms on cognitive functions and peripheral biomarkers in bipolar disorder

Objective A global approach to factors responsible for functional impairment in patients with BD is necessary. Method Ninety-three euthymic patients with BD [49 patients with SD (subthreshold depression) and 44 patients without SD] and 48 healthy controls were invited for evaluation of demographic, clinical, and cognitive characteristics. To define SD, the lower limit was HDRS ≥4 points and the upper limit was HDRS <9 points. Stroop test, California verbal learning test, digit-span test, controlled word association test, and clock drawing test were performed. Serum BDNF levels were measured. Additionally in the BD group; blood drug (lithium, valproic acid), leukocyte, C-reactive protein (CRP), TSH, and vitamin B12 levels were measured. Results We found no difference between serum BDNF levels of BD (n = 93) and controls. The cognitive performances of the BD group were worse than the control group (p < 0.001). Attention, working memory, and stroop performance of patients with SD were worse than patients without SD (p < 0.05). Verbal fluency, stroop test, and planning performance decreased as serum CRP level increased in patients with BD (p < 0.05). Conclusions Although the patient group with SD was in euthymia, their cognitive performance was worse than the group without SD. Poor cognitive performance in BD was associated with serum CRP levels.

Study of insight in patients with obsessive compulsive disorder and its relation to executive functions and serum brain-derived neurotrophic factor

BackgroundObsessive–compulsive disorder (OCD) is usually associated with insight’s heterogeneity, and those with poor insight showed lower BDNF and cognitive deficiencies. The aim was to detect the relation between insight to executive dysfunction and BDNF.Materials and methodsForty patients diagnosed with OCD and forty matched healthy controls. Also, both poor and good insight groups (assessed by The Brown Assessment of Belief Scale) were compared as regard Trail Making Test and serum level of BDNF).ResultsOCD patients group gave a significant worse performance in TMT and lower BDNF serum level than healthy control. Also, OCD patients with poor insight had lower BDNF level than patients with good to fair insight. ROC curve analysis confirmed that BDNF is a valuable diagnostic biomarker of insight in patients with OCD with 100% sensitivity and 72.41% specificity, p value < 0.001. Insight of OCD patients was not significantly associated with executive dysfunction detected by Trail Making Test.ConclusionsOCD patients with poor insight had longer duration of illness, severe OCD symptoms, lower serum BDNF level, and longer time on TMTA-B than good insight patients. BDNF is a valuable diagnostic biomarker of insight in patients with OCD.

Identification of myokines susceptible to improve glucose homeostasis after bariatric surgery.

The identification of myokines susceptible to improve glucose homeostasis following bariatric surgery could lead to new therapeutic approaches for type 2 diabetes. Changes in the Homeostasis Model Assessment (HOMA) test were assessed in patients before and 3 months after bariatric surgery. Changes in myokines expression and circulating levels were assessed using RT-qPCR and ELISA. Myokines known to regulate glucose homeostasis were identified using literature (Targeted study) and putative myokines using RNA-Sequencing (Untargeted study). A linear regression analysis adjusted for age and sex was used to search for associations between changes in the HOMA test and changes in myokines. In the targeted study, BDNF expression was upregulated (+30%, p=0.006) while BDNF circulating levels were decreased (-12%, p=0.001). Upregulated BDNF expression was associated with decreased HOMA-IR (adjusted estimate [95%CI]: -0.51 [-0.88; -0.13], p=0.010). Decreased BDNF serum levels were associated with decreased HOMA-B (adjusted estimate [95%CI] = 0.002 [0.00002-0.0031], p=0.046). In the untargeted study, upregulated putative myokines included XYLT1 (+64%, p<0.001), LGR5 (+57, p<0.001), and SPINK5 (+46%, p<0.001). Upregulated LGR5 was associated with decreased HOMA-IR (adjusted estimate -0.50 [-0.86; -0.13], p=0.009). Upregulated XYLT1 and SPINK5 were associated with increased HOMA-S (respectively, adjusted estimate [95%CI]: 109.1 [28.5; 189.8], p=0.009 and 16.5 [0.87; 32.19], p=0.039). Improved glucose homeostasis following bariatric surgery is associated with changes in myokines expression and circulating levels. In particular, upregulation of BDNF, XYLT1, SPINK5, and LGR5 is associated with improved insulin sensitivity. These results suggest that these myokines could contribute to improved glucose homeostasis following bariatric surgery.

Retrospective study on the correlation between serum MIF level and the condition and prognosis of patients with traumatic head injury.

This study aimed to investigate the correlation between serum levels of macrophage migration inhibitory factor (MIF) and the condition and prognosis of patients with traumatic brain injury (TBI). A retrospective study design was used, and the clinical data of 131 TBI patients from February 2019 to January 2022 were analyzed. Patients were divided into mild (13-15 points), moderate (9-12 points), or severe (3-8 points) groups according to their Glasgow Coma Scale (GCS) score after admission. The serum levels of BDNF, MIF, and MBP in the three groups were compared, and their correlation with the severity of TBI was analyzed. Patients were then separated into a good prognosis group (4-5 points) and a poor prognosis group (≤3 points) based on their Glasgow Prognostic Score (GOS) after 6 months of follow-up. The predictive power of serum indexes and combined detection on prognosis was analyzed. Patients were classified into a mild group (n = 63), moderate group (n = 47), and severe group (n = 21) based on their GCS, with a significant difference noted in serum levels of MIF, MBP, and BDNF among patients with different degrees of severity (all P < 0.001). The MIF, MBP, and BDNF levels were lower in the mild group compared to the moderate (all P < 0.001) and severe group (all P < 0.001). Additionally, the MIF and BDNF levels in the moderate group were lower compared to the severe group (P = 0.011, P = 0.002). Patients with mild severity had lower serum MIF, MBP, and BDNF levels than those with other degrees, and these indexes were positively correlated with the severity of TBI (all P < 0.001, r = 0.62, r = 0.48, r = 0.58). Based on the GOS, patients were divided into a good prognosis group (n = 107) and a poor prognosis group (n = 24), with the levels of MIF, MBP, and BDNF in the good prognosis group being significantly lower than those in the poor prognosis group (P < 0.001, P = 0.007, P = 0.003). The area under the curve (AUC) of MIF was higher than that of MBP and BDNF in predicting the prognosis of TBI patients; however, the statistical differences were not significant (MIF vs. MBP, P = 0.239; MIF vs. BDNF, P = 0.211; BDNF vs. MBP, P = 0.899). The center line has a large displacement, CT annular cisterna compression, increased white blood cell count, MBP and BDNF were risk factors for prognosis in TBI patients (P = 0.005, P = 0.001, P = 0.005, P = 0.033, P = 0.044). The serum levels of MIF, MBP, and BDNF in TBI patients were positively correlated with the severity of the disease, and MBP, BDNF levels had predictive value in determining patient prognosis.