Interactions of Glutamatergic Neurotransmission and Brain-Derived Neurotrophic Factor in the Regulation of Behaviors after Nicotine Administration

Kim, Jieun; Yang, Jialong; Ryu, In Soo; Sohn, Sumin; Kim, Sung-Hyun; Choe, Eun Sang

doi:10.3390/ijms20122943

Cited by 15 publications

(8 citation statements)

References 95 publications

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“…Most other studies found serotonergic or dopaminergic signaling to be involved in FP [18] and we recently re- based on genomic studies in the very same population as used in the current study [21,25]. Cholinergic signaling has not been implicated in FP so far, but is linked to both monoamine as well as GABAergic signaling and is implicated in certain psychiatric disorders [33]. In particular, α7 nAChRs have a crucial role in the dysfunction of cortical parvalbumin-positive GABAergic neurons, as seen in schizophrenia [34].…”

Section: Discussionmentioning

confidence: 78%

Analysis of the brain transcriptome in lines of laying hens divergently selected for feather pecking

et al. 2020

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Background: Feather pecking (FP) in laying hens reduces animal welfare and leads to economic losses for the layer industry. FP is considered a heritable condition that is influenced by dysregulation of neurotransmitter homeostasis, the gut microbiome, and the immune system. To identify genes and biological pathways responsible for FP behavior we compared the brain transcriptomes of 48 hens divergently selected for FP. In addition, we tested if high feather peckers (HFP) and low feather peckers (LFP) respond differently to light since light has been shown to trigger FP behavior. Results: Of approximately 48 million reads/sample an average of 98.4% were mapped to the chicken genome (GRCg6a). We found 13,070 expressed genes in the analyzed brains of which 423 showed differential expression between HFP and LFP. Genes of uncertain function and non-coding RNAs were overrepresented among those transcripts. Functional analyses revealed the involvement of cholinergic signaling, postsynaptic activity, membrane channels, and the immune system. After the light stimulus, 28 genes were found to be differentially expressed. These included an interaction cluster of core components of the circadian clock. However, differences in the response to light between HFP and LFP were not detectable. Conclusions: Genes involved in cholinergic signaling, channel activity, synaptic transmission, and immune response were found to be involved in FP behavior. We propose a model in which the gut microbiota modulates the immune system, which in turn affects cholinergic signaling. This might have an influence on monoamine signaling with possible involvement of GABA or glutamate signaling.

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Section: Discussionmentioning

confidence: 78%

Analysis of the brain transcriptome in lines of laying hens divergently selected for feather pecking

et al. 2020

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“…The BDNF expression is closely related to a7nAChRs (J. Kim et al, 2019;Moriguchi et al, 2020). Blocking a7nAChRs reduces the BDNF expression in the hippocampus (Freedman et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Ras Inhibitor Lonafarnib Rescues Structural and Functional Impairments of Synapses of Aβ_1-42 Mice via α7nAChR-Dependent BDNF Upregulation

Cai

Wang

et al. 2022

J. Neurosci.

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Alzheimer's disease (AD) is characterized pathologically by the structural and functional impairments of synapses in the hippocampus, inducing the learning and memory deficiencies. Ras GTPase is closely related to the synaptic function and memory. This study was to investigate the effects of farnesyl transferase inhibitor lonafarnib on the synaptic structure and function in AD male mice and explore the potential mechanism. Our results showed 50 mg/kg lonafarnib (intraperitoneal) rescued the impaired spatial memory and improved the damaged synaptic transmission and plasticity of Ab 1-42 mice. In addition, lonafarnib ameliorated the morphology of synaptic dendrites and spines in Ab 1-42 mice. Furthermore, lonafarnib enhanced a7nAChR cell surface expression and phosphorylation of downstream Akt and CaMKII in Ab 1-42 mice, which were inhibited by a7nAChR antagonist methyl lycaconitine (MLA), and increased the phosphorylation of CREB in a CaMKII-but not ERK-dependent way. Lonafarnib enhanced hippocampal brain-derived neurotrophic factor (BDNF) concentration in Ab 1-42 mice, which was sensitive to MLA and KN93 (an inhibitor of CaMKII), but not related to ERK and Akt pathways. H-Ras, but not Rhes, was related to the lonafarnib induced improvement of a7nAChR cell surface expression and BDNF content. Interestingly, lonafarnib induced improvement of synaptic transmission, plasticity and spatial cognition in Ab 1-42 mice was abolished by BDNF deprivation with TrkB/Fc chimera protein. Our results indicate that lonafarnib can rescue the structural and functional impairments of synapses in the Ab 1-42 mice, which may be related to the improvement of BDNF content through the H-Ras-a7nAChR-dependent CaMKII-CREB pathway, leading to the improvement of spatial cognition.

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“…Excitatory inputs from N-methyl-D-aspartate (NMDA) receptors in the VTA increase dopamine levels in the NAcc via activation of presynaptic nAChRs on glutamatergic terminals. Nicotine-induced dopamine levels are also modulated by inhibitory GABA-ergic input including GABA-ergic inhibitory afferents to VTA dopaminergic receptors, inhibitory GABA-ergic interneurons within the VTA and inhibitory medium spiny neurons in the NAcc (Kim et al 2019, Watkins, Koob, and Markou 2000, D’Souza and Markou 2013, Wills et al 2022, Pistillo et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Overexpression of Cancer- and Neurotransmitter-Associated Genes in the Nucleus Accumbens of Smokers

Mamdani

Bunney

Cartagena

et al. 2022

Preprint

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The effects of smoking in the human brain were explored at the molecular level in the nucleus accumbens (NAcc), a key brain region involved in tobacco addiction. Gene expression data from post-mortem NAcc were analyzed according to smoking habits: Never smokers, Former smokers and Current smokers at the time of death. The effect of smoking was determined using an ANCOVA model, controlling for potential confounders (psychiatric diagnosis, gender, age, post-mortem interval, and brain pH) followed by pair-wise post-hoc comparisons. Q-values (false discovery rate adjusted p-values) < 0.05 were used in combination with afold change of > ±1.3 to identify the most relevant genes. The greatest number of differentially expressed genes (DEGs) were found in subjects with a recent history of smoking (Current smokers) compared to either Former or Never smokers. Only two genes were differentially expressed between Former and Never smokers, suggesting that the effects of smoking on gene expression in the brain may be transient. Ingenuity Pathway Analysis (IPA) of DEGs identified a significant over-representation of neurotransmitter system genes (glutamate, GABA) in Current smokers. IPA also revealed many genes associated with cancer in Current smokers compared to Former and Never smokers despite no known cancer in any subjects. Genes associated with neoplasms, glioblastoma, gliomas and tumor regulations are among the top 10 transcripts. Our findings show that active smokers have a significant increase in cancer-related genes and alterations in glutamate and GABA neurotransmitter systems in the NAcc. To our knowledge this is the first study to identify cancer-related genes in the NAcc in Current smokers who have no evidence of cancer.

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Interactions of Glutamatergic Neurotransmission and Brain-Derived Neurotrophic Factor in the Regulation of Behaviors after Nicotine Administration

Cited by 15 publications

References 95 publications

Analysis of the brain transcriptome in lines of laying hens divergently selected for feather pecking

Analysis of the brain transcriptome in lines of laying hens divergently selected for feather pecking

Ras Inhibitor Lonafarnib Rescues Structural and Functional Impairments of Synapses of Aβ_1-42 Mice via α7nAChR-Dependent BDNF Upregulation

Overexpression of Cancer- and Neurotransmitter-Associated Genes in the Nucleus Accumbens of Smokers

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Interactions of Glutamatergic Neurotransmission and Brain-Derived Neurotrophic Factor in the Regulation of Behaviors after Nicotine Administration

Cited by 15 publications

References 95 publications

Analysis of the brain transcriptome in lines of laying hens divergently selected for feather pecking

Analysis of the brain transcriptome in lines of laying hens divergently selected for feather pecking

Ras Inhibitor Lonafarnib Rescues Structural and Functional Impairments of Synapses of Aβ1-42 Mice via α7nAChR-Dependent BDNF Upregulation

Overexpression of Cancer- and Neurotransmitter-Associated Genes in the Nucleus Accumbens of Smokers

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Ras Inhibitor Lonafarnib Rescues Structural and Functional Impairments of Synapses of Aβ_1-42 Mice via α7nAChR-Dependent BDNF Upregulation