Region-specific expression of precursor and mature brain-derived neurotrophic factors after chronic alcohol exposure

Yang, Jinwei; Ma, Wei; Yang, Yanlei; Wang, Xianbin; Li, Xing-Tong; Wang, Tongtong; Wang, Xiangpeng; Gao, Wei; Li, Junyan; Zhou, Xin‐Fu; Guo, Jun; Li, Liyan

doi:10.1080/00952990.2016.1263642

Cited by 9 publications

(6 citation statements)

References 36 publications

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“…Indeed, it has been previously described that sortilin, an intracellular chaperon, acts as a regulatory switch for delivery of BDNF to the regulatory secretory pathway or to degradation in the lysosome, modulating in this way the neurotrophic factor availability (Evans et al, 2011). Interestingly, BDNF levels have been shown to be modified in PFC after chronic ethanol exposure (Yang et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Ibogaine Administration Modifies GDNF and BDNF Expression in Brain Regions Involved in Mesocorticolimbic and Nigral Dopaminergic Circuits

et al. 2019

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Ibogaine is an atypical psychedelic alkaloid, which has been subject of research due to its reported ability to attenuate drug-seeking behavior. Recent work has suggested that ibogaine effects on alcohol self-administration in rats are related to the release of Glial cell Derived Neurotrophic Factor (GDNF) in the Ventral Tegmental Area (VTA), a mesencephalic region which hosts the soma of dopaminergic neurons. Although previous reports have shown ibogaine’s ability to induce GDNF expression in rat midbrain, there are no studies addressing its effect on the expression of GDNF and other neurotrophic factors (NFs) such as Brain Derived Neurotrophic Factor (BDNF) or Nerve Growth Factor (NGF) in distinct brain regions containing dopaminergic neurons. In this work, we examined the effect of ibogaine acute administration on the expression of these NFs in the VTA, Prefrontal Cortex (PFC), Nucleus Accumbens (NAcc) and the Substantia Nigra (SN). Rats were i.p. treated with ibogaine 20 mg/kg (I20), 40 mg/kg (I40) or vehicle, and NFs expression was analyzed after 3 and 24 h. At 24 h an increase of the expression of the NFs transcripts was observed in a site and dose dependent manner. Only for I40, GDNF was selectively upregulated in the VTA and SN. Both doses elicited a large increase in the expression of BDNF transcripts in the NAcc, SN and PFC, while in the VTA a significant effect was found only for I40. Finally, NGF mRNA was upregulated in all regions after I40, while I20 showed a selective upregulation in PFC and VTA. Regarding protein levels, an increase of GDNF was observed in the VTA only for I40 but no significant increase for BDNF was found in all the studied areas. Interestingly, an increase of proBDNF was detected in the NAcc for both doses. These results show for the first time a selective increase of GDNF specifically in the VTA for I40 but not for I20 after 24 h of administration, which agrees with the effective dose found in previous self-administration studies in rodents. Further research is needed to understand the contribution of these changes to ibogaine’s ability to attenuate drug-seeking behavior.

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Section: Discussionmentioning

confidence: 99%

Ibogaine Administration Modifies GDNF and BDNF Expression in Brain Regions Involved in Mesocorticolimbic and Nigral Dopaminergic Circuits

et al. 2019

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“…Little is known about their levels in the diseased conditions. Chronic ethanol exposure can also remodel the BDNF gene at the chromatin level, contribute to the development and maintenance of addiction 13–15 . The BDNF and TrkB levels decreased in alcohol-dependent patients, increased after abstinence.…”

Section: Introductionmentioning

confidence: 99%

ProBDNF/p75NTR/sortilin pathway is activated in peripheral blood of patients with alcohol dependence

et al. 2018

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Alcohol dependence is a worldwide problem with a great social and economic burden in many countries. A number of studies have suggested that BDNF (mature BDNF) and its precursor (proBDNF) play important roles in the alcohol dependence. However, what roles of the mBDNF/proBDNF pathways play during the pathological process of alcohol dependence are not clearly understood. In our clinical study, peripheral blood was sampled from 30 male patients with alcohol dependence and 50 healthy males (as control). The protein levels of proBDNF, p75NTR, sortilin, mBDNF, TrkB and mRNA levels of BDNF, p75NTR, sortilin, and TrkB were detected in the peripheral blood in our study. We found that the protein levels of proBDNF and p75NTR were increased, but not the sortilin protein level; while the TrkB protein level was decreased in the alcohol dependence patients compared with healthy controls. Moreover, the mRNA levels of p75NTR and sortilin from the lymphocytes were slightly increased; while BDNF and TrkB were significantly decreased. The ELISA results of mBDNF and TrkB were declined in the alcohol dependence group. The levels of mBDNF and TrkB were negatively correlated with the average amount of daily ethanol consumption, and the levels of proBDNF, p75NTR and sortilin were positively correlated with the average amount of ethanol consumption per day. The ratio of proBDNF to mBDNF was altered in alcohol dependence patients. The balance between the proBDNF/p75NTR and mBDNF/TrkB signalling pathways appeared dysregulated in alcohol dependence. Our results suggested that both pathways may participate in the complex processes of alcohol dependence.

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“…For instance, both of these treatments produce forebrain cholinergic cell loss, reductions in hippocampal acetylcholine (Anzalone et al., ; Hall and Savage, ; Pires et al., , ), and reductions in hippocampal neurotrophin levels (Davis, ; Hellmann et al., ; Miller and Mooney, ; Vedder et al., ). Within the frontal cortex, there is shrinkage of both gray and white matter (He et al., ; Langlais and Savage, ; Savage et al., ) as well as a change of neurotrophin levels (Vedder et al., ; Yang et al., ). Interestingly, lesions in thalamus and cell loss in mammillary bodies are found uniquely in TD animals.…”

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confidence: 99%

A Pivotal Role for Thiamine Deficiency in the Expression of Neuroinflammation Markers in Models of Alcohol‐Related Brain Damage

Nunes

Vedder

Deak

et al. 2019

Alcoholism Clin & Exp Res

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Background Alcohol‐related brain damage (ARBD) is associated with neurotoxic effects of heavy alcohol use and nutritional deficiency, in particular thiamine deficiency (TD), both of which induce inflammatory responses in brain. Although neuroinflammation is a critical factor in the induction of ARBD, few studies have addressed the specific contribution(s) of ethanol (EtOH) versus TD. Methods Adult rats were randomly divided into 6 conditions: chronic EtOH treatment (CET) where rats consumed a 20% v/v solution of EtOH for 6 months; CET with injections of thiamine (CET + T); severe pyrithiamine‐induced TD (PTD); moderate PTD; moderate PTD during CET; and pair‐fed controls. After the treatments, the rats were split into 3 recovery phase time points: the last day of treatment (time point 1), acute recovery (time point 2: 24 hours posttreatment), and delayed recovery (time point 3: 3 weeks posttreatment). At these time points, vulnerable brain regions (thalamus, hippocampus, frontal cortex) were collected and changes in neuroimmune markers were assessed using a combination of reverse transcription polymerase chain reaction and protein analysis. Results CET led to minor fluctuations in neuroimmune genes, regardless of the structure being examined. In contrast, PTD treatment led to a profound increase in neuroimmune genes and proteins within the thalamus. Cytokine changes in the thalamus ranged in magnitude from moderate (3‐fold and 4‐fold increase in interleukin‐1β [IL‐1β] and IκBα) to severe (8‐fold and 26‐fold increase in tumor necrosis factor‐α and IL‐6, respectively). Though a similar pattern was observed in the hippocampus and frontal cortex, overall fold increases were moderate relative to the thalamus. Importantly, neuroimmune gene induction varied significantly as a function of severity of TD, and most genes displayed a gradual recovery across time. Conclusions These data suggest an overt brain inflammatory response by TD and a subtle change by CET alone. Also, the prominent role of TD in the immune‐related signaling pathways leads to unique regional and temporal profiles of induction of neuroimmune genes.

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Region-specific expression of precursor and mature brain-derived neurotrophic factors after chronic alcohol exposure

Abstract: Chronic alcohol exposure induced the region-specific expression of BDNF and proBDNF and their respective receptors in the brain. These results suggest that BDNF and proBDNF signaling pathways may play major roles in alcohol preference and addiction.

Cited by 9 publications

References 36 publications

Ibogaine Administration Modifies GDNF and BDNF Expression in Brain Regions Involved in Mesocorticolimbic and Nigral Dopaminergic Circuits

Ibogaine Administration Modifies GDNF and BDNF Expression in Brain Regions Involved in Mesocorticolimbic and Nigral Dopaminergic Circuits

ProBDNF/p75NTR/sortilin pathway is activated in peripheral blood of patients with alcohol dependence

A Pivotal Role for Thiamine Deficiency in the Expression of Neuroinflammation Markers in Models of Alcohol‐Related Brain Damage

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