Browsing by Subject "BDNF"

Now showing 1 - 8 of 8
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    Associations of brain-derived neurotrophic factor rs6265 polymorphism and cognitive function in breast cancer survivors from a cross-sectional study
    (Wiley, 2024) Goto, Taichi; Saligan, Leorey N.; Li, Xiaobai; Xiang, Lichen; Kwiat, Catherine; Nguyen, Christopher; Crouch, Adele; Von Ah, Diane; School of Nursing
    Background: Breast cancer survivors (BCS) often complain of cancer-related cognitive impairment (CRCI) during and even months after completing primary cancer treatments, particularly chemotherapy. The etiology of CRCI is unknown, but associations of CRCI with germline genetic polymorphisms have been reported, including Brain-Derived Neurotrophic Factor (BDNF) rs6265 polymorphism. The current study investigated the associations of specific BDNF rs6265 with CRCI. Methods: Cancer-related cognitive impairment was assessed using subjective reports of cognitive symptoms (the version 1.0, 8-item short-forms of the Patient-Reported Outcomes Measurement Information System®) and computerized objective cognitive function scores (CANTAB®). BDNF rs6265 genotypes were determined from buccal swabs. The associations of specific BDNF rs6265 with CRCI were examined by either one-way analysis of variance or the Kruskal–Wallis test followed by post hoc tests and rank-based regression analysis. Results: We examined 356 female BCS. The mean (SD) age was 55.6 (9.8) years old, the median (IQR) years since cancer diagnosis were 4.0 (6.0), and 331 (92.7%) were self-described as White. BCS carrying the Met/Met genotype showed poorer results on ‘visual episodic memory and new learning’ and ‘spatial working memory and executive function.’ This relationship was observed regardless of prior chemotherapy. Conclusion: Our findings suggest that carrying the BDNF rs6265 Met/Met genotype increases the risk for CRCI in BCS. These results are foundational in nature and provide important information to identify mechanisms underpinning CRCI.
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    Co‐administration of ethanol and nicotine heightens sensitivity to ethanol reward within the nucleus accumbens (NAc) shell and increasing NAc shell BDNF is sufficient to enhance ethanol reward in naïve Wistar rats
    (Wiley, 2019) Waeiss, Robert A.; Knight, Christopher P.; Engleman, Eric A.; Hauser, Sheketha R.; Rodd, Zachary A.; Psychiatry, School of Medicine
    Alcohol use disorder most commonly presents as a polydrug disorder where greater than 85% are estimated to smoke. EtOH and nicotine (NIC) co‐abuse or exposure results in unique neuroadaptations that are linked to behaviors that promote drug use. The current experiments aimed to identify neuroadaptations within the mesolimbic pathway produced by concurrent EtOH and NIC exposure. The experiments used four overall groups of male Wistar rats consisting of vehicle, EtOH or NIC alone, and EtOH+NIC. Drug exposure through direct infusion into the posterior ventral tegmental area (pVTA) stimulated release of glutamate and dopamine in the nucleus accumbens (NAc) shell, which was quantified through high‐performance liquid chromatography. Additionally, brain‐derived neurotrophic factor (BDNF) protein levels were measured via enzyme‐linked immunosorbent assay (ELISA). A second experiment investigated the effects of drug pretreatment within the pVTA on the reinforcing properties of EtOH within the NAc shell through intracranial self‐administration (ICSA). The concluding experiment evaluated the effect of NAc shell pretreatment with BDNF on EtOH reward utilizing ICSA within that region. The data indicated that only EtOH+NIC administration into the pVTA simultaneously increased glutamate, dopamine, and BDNF in the NAc shell. Moreover, only pVTA pretreatment with EtOH+NIC enhanced the reinforcing properties of EtOH in the NAc shell. BDNF pretreatment in the NAc shell was also sufficient to enhance the reinforcing properties of EtOH in the NAc shell. The collected data suggest that concurrent EtOH+NIC exposure results in a distinct neurochemical response and neuroadaptations within the mesolimbic pathway that alter EtOH reward.
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    Effects of chronic ethanol consumption on the expression of GLT-1 and neuroplasticity-related proteins in the nucleus accumbens of alcohol-preferring rats
    (Elsevier, 2020-12) Alhaddad, Hasan; Alasmari, Fawaz; Alhamadani, Balsam; Wong, Woonyen; Bell, Richard L.; Sari, Youssef; Psychiatry, School of Medicine
    Chronic ethanol exposure induces impairments in CNS excitatory and inhibitory activity. These impairments are associated with glutamatergic dysfunction, including altered neuroplasticity. This study examined the effects of 6-week ethanol (15% and 30% v/v) consumption, by male alcohol-preferring P rats, on protein expression associated with neuroplasticity and glutamate transporter-1 (GLT-1) function. The latter regulates intra- and extra-synaptic glutamate levels. We focused on the shell and core subregions of the nucleus accumbens (Acb); i.e., shell (AcbSh) and core (AcbCo), for these measures. Chronic ethanol exposure increased the expression of BDNF, Arc and phosphorylated (p)-post-synaptic density protein-95 (p-PSD-95) in the AcbSh of P rats. Moreover, the ratio of phospho-neuronal nitric oxide synthase (p-nNOS) to total nNOS was also increased in the AcbSh. These changes in BDNF, Arc and p-nNOS/nNOS ratio were not observed in the AcbCo. Furthermore, chronic ethanol consumption reduced GLT-1 expression in the AcbSh. Alternatively, treatment with ceftriaxone (CEF), a known GLT-1 upregulator, abolished the effect of chronic ethanol consumption on BDNF expression in the AcbSh. Overall, the present findings confirm that chronic ethanol consumption modulates activity-associated synaptic proteins, including BDNF, Arc and nNOS in a subregion-specific (i.e., in the AcbSh but not AcbCo) manner. Thus, alterations in mesocorticolimbic glutamatergic homeostasis and neuroplasticity are possible functional targets for the treatment of alcohol use disorders.
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    Examining Relationships Among Depression Treatment, Brain-Derived Neurotrophic Factor (BDNF), and Depressive Symptom Clusters in Primary Care Patients with Depression
    (2023-05) Crawford, Christopher A.; Stewart, Jesse; Rand, Kevin; Wu, Wei
    Depression is a heterogeneous mental health condition, varying in presentation across individuals. A candidate etiology that may help account for this heterogeneity is the neurotrophin hypothesis of depression, which proposes that stress downregulates brain-derived neurotrophic factor (BDNF) expression, leading to aberrant neurogenesis and depression. This etiology may manifest in a distinct symptom profile that may be reflected in depressive symptoms or symptom clusters. The effect of psychological interventions on BDNF is not known. Additionally, it is not known if BDNF levels mediate intervention effects on depressive symptom clusters. Using data from the eIMPACT trial (NCT02458690, supported by R01 HL122245), I examined baseline associations of BDNF with depressive symptoms and depressive symptom clusters. Also, I examined if the modernized collaborative care intervention for depression (internet CBT, telephonic CBT, and select antidepressant medications) affected BDNF and if changes in BDNF mediated intervention effects on cognitive/affective and somatic depressive symptom clusters. 216 participants (primary care patients with depression and elevated cardiovascular disease risk ≥50 years from a safety net healthcare system) were randomized to 12 months of the eIMPACT intervention (n=107) or usual primary care for depression (primary care providers supported by embedded behavioral health clinicians and affiliated psychiatrists; n=109). Plasma BDNF was measured with commercial ELISA kits. Depressive symptoms were assessed by the PHQ-9 (M=15.1, SD=5.0) from which cognitive/affective and somatic subscale scores were computed. No significant baseline associations were observed between BDNF and individual depressive symptoms or depressive symptom clusters. The intervention did not improve BDNF over 12 months. Similarly, 12-month changes in BDNF were not associated with 12-month changes in PHQ-9 cognitive/affective or somatic subscale scores. However, the intervention significantly improved PHQ-9 cognitive/affective and somatic subscale scores over 12 months. 12-month changes in BDNF did not mediate the effect of the intervention on 12-month changes in the PHQ-9 subscale scores. These findings suggest that modernized collaborative care for depression does not improve BDNF. Modernized collaborative care does yield improvements in both cognitive/affective and somatic depressive symptom clusters, albeit not via changes in BDNF.
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    Harmine Ameliorates Cognitive Impairment by Inhibiting NLRP3 Inflammasome Activation and Enhancing the BDNF/TrkB Signaling Pathway in STZ-Induced Diabetic Rats
    (Frontiers Media, 2020-05-01) Liu, Peifang; Li, Hui; Wang, Yueqiu; Su, Xiaolin; Li, Yang; Yan, Meiling; Ma, Lan; Che, Hui; Biochemistry and Molecular Biology, School of Medicine
    Diabetes mellitus (DM) is considered a risk factor for cognitive dysfunction. Harmine not only effectively improves the symptoms of DM but also provides neuroprotective effects in central nervous system diseases. However, whether harmine has an effect on diabetes-induced cognitive dysfunction and the underlying mechanisms remain unknown. In this study, the learning and memory abilities of rats were evaluated by the Morris water maze test. Changes in the nucleotide-binding oligomerization domain-containing protein (NOD)-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome and brain-derived neurotrophic factor (BDNF)/TrkB signaling pathway were determined in both streptozotocin (STZ)-induced diabetic rats and high glucose (HG)-treated SH-SY5Y cells by western blotting and histochemistry. Herein, we found that harmine administration significantly ameliorated learning and memory impairment in diabetic rats. Further study showed that harmine inhibited NLRP3 inflammasome activation, as demonstrated by reduced NLRP3, ASC, cleaved caspase-1, IL-1β, and IL-18 levels, in the cortex of harmine-treated rats with DM. Harmine was observed to have similar beneficial effects in HG-treated neuronal cells. Moreover, we found that harmine treatment enhanced BDNF and phosphorylated TrkB levels in both the cortex of STZ-induced diabetic rats and HG-treated cells. These data indicate that harmine mitigates cognitive impairment by inhibiting NLRP3 inflammasome activation and enhancing the BDNF/TrkB signaling pathway. Thus, our findings suggest that harmine is a potential therapeutic drug for diabetes-induced cognitive dysfunction.
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    Inhibition of tropomyosine receptor kinase B on the migration of human Schwann cell and dispersion of oral tongue squamous cell carcinoma in vitro
    (Wiley, 2019-12) Ein, Liliana; Bracho, Olena; Mei, Christine; Patel, Jaimin; Boyle, Thomas; Monje, Paula; Fernandez‐Valle, Cristina; Bas, Esperanza; Thomas, Giovana; Weed, Donald; Sargi, Zoukaa; Dinh, Christine; Neurological Surgery, School of Medicine
    Background Schwann cells (SC) may play an important role in perineural invasion (PNI) by promoting cancer cell dispersion. Brain‐derived neurotrophic factor (BDNF) may contribute to these cellular events by activating tropomyosine receptor kinase B (TrkB). This study examines the effect of TrkB inhibition on SC migration and oral cancer cell dispersion in vitro. Methods Human tongue squamous cell carcinoma (SCC‐9) and human SCs were cocultured in three different conditioned mediums: control, BDNF, and TrkB inhibitor. Cell migration, cancer cell dispersion, and SC dedifferentiation were measured on time‐lapse and immunofluorescence images. Results Cancer cell migration exceeded SC migration in all conditions. TrkB inhibition promoted SC dedifferentiation and significantly increased SC migration, when compared to BDNF conditions. TrkB inhibition also reduced cancer cell dispersion, when compared to control and BDNF‐treated cultures. Conclusion SCs may have importance in the pathophysiology of PNI. TrkB inhibition may be a potential avenue for therapeutic intervention.
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    Npy deletion in an alcohol non-preferring rat model elicits differential effects on alcohol consumption and body weight.
    (Elsevier, 2016-07-20) Qiu, Bin; Bell, Richard L.; Cao, Yong; Zhang, Lingling; Stewart, Robert B.; Graves, Tamara; Lumeng, Lawrence; Yong, Weidong; Liang, Tiebing; Department of Psychiatry, IU School of Medicine
    Neuropeptide Y (NPY) is widely expressed in the central nervous system and influences many physiological processes. It is located within the rat quantitative trait locus (QTL) for alcohol preference on chromosome 4. Alcohol-nonpreferring (NP) rats consume very little alcohol, but have significantly higher NPY expression in the brain than alcohol-preferring (P) rats. We capitalized on this phenotypic difference by creating an Npy knockout (KO) rat using the inbred NP background to evaluate NPY effects on alcohol consumption. Zinc finger nuclease (ZNF) technology was applied, resulting in a
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    The p53 Pathway Controls SOX2-Mediated Reprogramming in the Adult Mouse Spinal Cord
    (Elsevier, 2016-10-11) Wang, Lei-Lei; Su, Zhida; Tai, Wenjiao; Zou, Yuhua; Xu, Xiao-Ming; Zhang, Chun-Li; Department of Neurological Surgery, IU School of Medicine
    Although the adult mammalian spinal cord lacks intrinsic neurogenic capacity, glial cells can be reprogrammed in vivo to generate neurons after spinal cord injury (SCI). How this reprogramming process is molecularly regulated, however, is not clear. Through a series of in vivo screens, we show here that the p53-dependent pathway constitutes a critical checkpoint for SOX2-mediated reprogramming of resident glial cells in the adult mouse spinal cord. While it has no effect on the reprogramming efficiency, the p53 pathway promotes cell-cycle exit of SOX2-induced adult neuroblasts (iANBs). As such, silencing of either p53 or p21 markedly boosts the overall production of iANBs. A neurotrophic milieu supported by BDNF and NOG can robustly enhance maturation of these iANBs into diverse but predominantly glutamatergic neurons. Together, these findings have uncovered critical molecular and cellular checkpoints that may be manipulated to boost neuron regeneration after SCI.