Choline Transporter CHT Regulation and Function in Cholinergic Neurons

2012 ◽  
Vol 12 (2) ◽  
pp. 114-121 ◽  
Author(s):  
Stefanie A.G. Black ◽  
R. Jane Rylett
Keyword(s):  
Cholinergic Neurons ◽  
Choline Transporter ◽  
And Function

Glutamate elicits release of BDNF from basal forebrain astrocytes in a process dependent on metabotropic receptors and the PLC pathway

2008 ◽  
Vol 4 (1) ◽  
pp. 35-42 ◽  
Author(s):  
Ying Y. Jean ◽  
Lauren D. Lercher ◽  
Cheryl F. Dreyfus
Keyword(s):  
Basal Forebrain ◽  
Metabotropic Glutamate Receptors ◽  
Cholinergic Neurons ◽  
Metabotropic Receptors ◽  
Western Blots ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Initial Work ◽  
Neuronal Signal ◽  
And Function

A key neurotrophin responsible for the survival and function of basal forebrain (BF) cholinergic neurons is brain-derived neurotrophic factor (BDNF). A number of studies now indicate that a source of this factor may be BF astrocytes. This study was designed to define the role of BF-astrocyte-derived BDNF on cholinergic neurons. Moreover, it investigated regulatory events that modulate BDNF content and release. In initial work BDNF derived from BF-astrocyte-conditioned medium (ACM) was found to increase both numbers of BF acetylcholinesterase (AChE+) cholinergic neurons and the cholinergic synthetic enzyme choline acetyltransferase (ChAT). Western blots, immunocytochemistry and pharmacological inhibition studies revealed that glutamate, through group I metabotropic glutamate receptors (mGluR), increases the intracellular levels of BDNF in BF astrocytes in culture, as well as its release. Furthermore, the release of BDNF is mediated by the actions of PLC, IP3 and internal stores of Ca2+. These results suggest that BF astrocytes serve as local sources of BDNF for cholinergic neurons, and that they may be regulated as such by the neuronal signal, glutamate, through the mediation of group I metabotropic receptors and the PLC pathway.

scholarly journals Cholinergic Degeneration and Alterations in the TrkA and p75NTR Balance as a Result of Pro-NGF Injection into Aged Rats

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Ashley M. Fortress ◽  
Mona Buhusi ◽  
Kris L. Helke ◽  
Ann-Charlotte E. Granholm
Keyword(s):  
Basal Forebrain ◽  
Cholinergic Neurons ◽  
Memory Impairments ◽  
Age Related ◽  
High Affinity Receptor ◽  
Affinity Receptor ◽  
Cholinergic Degeneration ◽  
And Function ◽  
Do So

Learning and memory impairments occurring with Alzheimer's disease (AD) are associated with degeneration of the basal forebrain cholinergic neurons (BFCNs). BFCNs extend their axons to the hippocampus where they bind nerve growth factor (NGF) which is retrogradely transported to the cell body. While NGF is necessary for BFCN survival and function via binding to the high-affinity receptor TrkA, its uncleaved precursor, pro-NGF has been proposed to induce neurodegeneration via binding to the p75NTR and its coreceptor sortilin. Basal forebrain TrkA and NGF are downregulated with aging while pro-NGF is increased. Given these data, the focus of this paper was to determine a mechanism for how pro-NGF accumulation may induce BFCN degeneration. Twenty-four hours after a single injection of pro-NGF into hippocampus, we found increased hippocampal p75NTR levels, decreased hippocampal TrkA levels, and cholinergic degeneration. The data suggest that the increase in p75NTR with AD may be mediated by elevated pro-NGF levels as a result of decreased cleavage, and that pro-NGF may be partially responsible for age-related degenerative changes observed in the basal forebrain. This paper is the firstin vivoevidence that pro-NGF can affect BFCNs and may do so by regulating expression of p75NTR neurotrophin receptors.

scholarly journals Choline Transporter regulates olfactory habituation via a neuronal triad of excitatory, inhibitory and mushroom body neurons

PLoS Genetics ◽  
2021 ◽  
Vol 17 (12) ◽  
pp. e1009938
Author(s):  
Runa Hamid ◽  
Hitesh Sonaram Sant ◽  
Mrunal Nagaraj Kulkarni
Keyword(s):  
Cholinergic Neurons ◽  
Autism Spectrum ◽  
Inhibitory Neurons ◽  
Projection Neurons ◽  
Dependent Manner ◽  
Choline Transporter ◽  
Memory Processing ◽  
Stimulus Suppression ◽  
Incoming Stimulus

Choline is an essential component of Acetylcholine (ACh) biosynthesis pathway which requires high-affinity Choline transporter (ChT) for its uptake into the presynaptic terminals of cholinergic neurons. Previously, we had reported a predominant expression of ChT in memory processing and storing region of the Drosophila brain called mushroom bodies (MBs). It is unknown how ChT contributes to the functional principles of MB operation. Here, we demonstrate the role of ChT in Habituation, a non-associative form of learning. Odour driven habituation traces are laid down in ChT dependent manner in antennal lobes (AL), projection neurons (PNs), and MBs. We observed that reduced habituation due to knock-down of ChT in MBs causes hypersensitivity towards odour, suggesting that ChT also regulates incoming stimulus suppression. Importantly, we show for the first time that ChT is not unique to cholinergic neurons but is also required in inhibitory GABAergic neurons to drive habituation behaviour. Our results support a model in which ChT regulates both habituation and incoming stimuli through multiple circuit loci via an interplay between excitatory and inhibitory neurons. Strikingly, the lack of ChT in MBs shows characteristics similar to the major reported features of Autism spectrum disorders (ASD), including attenuated habituation, sensory hypersensitivity as well as defective GABAergic signalling. Our data establish the role of ChT in habituation and suggest that its dysfunction may contribute to neuropsychiatric disorders like ASD.

Survival, growth and function of damaged cholinergic neurons

1989 ◽  
pp. 259-274 ◽  
Author(s):  
Fred H. Gage ◽  
Mark H. Tuszynski ◽  
Karen S. Chen ◽  
David Armstrong ◽  
György Buzsàki
Keyword(s):  
Cholinergic Neurons ◽  
And Function

scholarly journals Syntheses and In-vitro Evaluation of Tetrahydroaminoacridine (THA) Based Analogues as High Affinity Choline Transporter (HAChT) Imaging Probe

2016 ◽  
Vol 17 (2) ◽  
pp. 97-102
Author(s):  
Mohammad Anwar Ul Azim ◽  
Takashi Kozaka ◽  
Izumi Uno ◽  
Daisuke Miwa ◽  
Yoji Kitamura ◽  
...  
Keyword(s):  
Binding Assay ◽  
Research Work ◽  
Cholinergic Neurons ◽  
Choline Uptake ◽  
Choline Transporter ◽  
High Affinity ◽  
20 Nm ◽  
High Affinity Choline Transporter

Introduction: In cholinergic neurons, high affinity choline uptake (HACU) by the high affinity choline transporter (HAChT) is a rate-limiting and regulatory step for the synthesis of Acetylcholine (Ach).Thus, HAChT appear to be a relatively specific presynaptic marker for cholinergic neurons in Alzheimer’s disease.Objectives: The principle objective of the study is to check the affinity of tetrahydroaminoacridine (THA) derivatives for HAChT. Another objective of the research work is to clarify whether the hemicholinium-3 (ChT inhibitor) and HACU enhancer molecules share the same binding sites or not.Materials and Methods: The inhibition activities of tacrine, the 2,3-dimethylfuran derivative of tacrine (DMTA) and their corresponding 2-oxo-1-pyrrolidineacetyl derivatives, namely PTAA and MKC-231 were measured by displacement of a typical HAChT antagonist [3H]HC-3 in rat cerebral membrane. The percentage of inhibition against the binding of [3H]HC-3 to HAChT were calculated using GraphPad Prism v4 software.Results: Hemicholinium-3 showed affinity for HAChT (IC50 = 20 nM) in the in vitro binding assay. A very insignificant inhibition activity (IC50 = 1000 nM) of Tacrine was revealed. The newly synthesized tacrine derivatives, DMTA and PTAA did not show any affinity for HAChT. Although MKC-231 was reported to enhance cholinergic activity at synaptic terminals, it did not show any affinity for the HAChT in [3H]HC-3 binding assay.Conclusion: In vitro [3H]HC-3 binding assay revealed no affinity of MKC-231, tacrine and its corresponding2-oxo-1-pyrrolidineacetate derivative towards HAChT. So, it is worthy to develop radiolabeled HC-3 derivatives with high affinity for HAChT, which can diffuse the BBB, to enable the in vivo investigation of HACU system.Bangladesh J. Nuclear Med. 17(2): 97-102, July 2014

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