Neuroprotective Actions of Dietary Choline

Blusztajn, Jan Krzysztof; Slack, Barbara E.; Mellott, Tiffany J.

doi:10.3390/nu9080815

Cited by 187 publications

(118 citation statements)

References 233 publications

Supporting

Mentioning

102

Contrasting

Unclassified

Order By: Relevance

“…For example, there is evidence that PUFA-containing LPI is important for cortical lamination and neuronal migration 70,71 . Lysophosphatidylcholine maybe essential in human brain development and function because they provide a preformed phospholipid source for membrane repair and supply essential PUFA species 72,73 . Elevated brain LPS levels, particularly very-long-chain species, results in a neuroinflammatory response that may promote microglial and neurobehavioral abnormalities 74 .…”

Section: Discussionmentioning

confidence: 99%

Aberrant cardiolipin metabolism is associated with cognitive deficiency and hippocampal alteration in tafazzin knockdown mice

Cole

Kim

Amoscato

et al. 2018

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

View full text Add to dashboard Cite

Cardiolipin (CL) is a key mitochondrial phospholipid essential for mitochondrial energy production. CL is remodeled from monolysocardiolipin (MLCL) by the enzyme tafazzin (TAZ). Loss-of-function mutations in the gene which encodes TAZ results in a rare X-linked disorder called Barth Syndrome (BTHS). The mutated TAZ is unable to maintain the physiological CL:MLCL ratio, thus reducing CL levels and affecting mitochondrial function. BTHS is best known as a cardiac disease, but has been acknowledged as a multi-syndrome disorder, including cognitive deficits. Since reduced CL levels has also been reported in numerous neurodegenerative disorders, we examined how TAZ-deficiency impacts cognitive abilities, brain mitochondrial respiration and the function of hippocampal neurons and glia in TAZ knockdown (TAZ kd) mice. We have identified for the first time the profile of changes that occur in brain phospholipid content and composition of TAZ kd mice. The brain of TAZ kd mice exhibited reduced TAZ protein expression, reduced total CL levels and a 19-fold accumulation of MLCL compared to wild-type littermate controls. TAZ kd brain exhibited a markedly distinct profile of CL and MLCL molecular species. In mitochondria, the activity of complex I was significantly elevated in the monomeric and supercomplex forms with TAZ-deficiency. This corresponded with elevated mitochondrial state I respiration and attenuated spare capacity. Furthermore, the production of reactive oxygen species was significantly elevated in TAZ kd brain mitochondria. While motor function remained normal in TAZ kd mice, they showed significant memory deficiency based on novel object recognition test. These results correlated with reduced synaptophysin protein levels and derangement of the neuronal CA1 layer in hippocampus. Finally, TAZ kd mice had elevated activation of brain immune cells, microglia compared to littermate controls. Collectively, our findings demonstrate that TAZ-mediated remodeling of CL contributes significantly to the expansive distribution of CL molecular species in the brain, plays a key role in mitochondria respiratory activity, maintains normal cognitive function, and identifies the hippocampus as a potential therapeutic target for BTHS.

show abstract

Section: Discussionmentioning

confidence: 99%

Aberrant cardiolipin metabolism is associated with cognitive deficiency and hippocampal alteration in tafazzin knockdown mice

Cole

Kim

Amoscato

et al. 2018

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

View full text Add to dashboard Cite

show abstract

“…A potential therapeutic strategy for BFCN degeneration with translational potential is perinatal maternal choline supplementation (MCS). In the developing fetus, choline is involved in effective neural tube closure, organogenesis, central nervous system cell membrane synthesis, and gene expression related to altering DNA methylation (Zeisel and Blusztajn, 1994;Blusztajn et al, 1998;Zeisel, 2000;Fisher et al, 2001;Cooney et al, 2002;Niculescu et al, 2004;Wurtman et al, 2009;Blusztajn et al, 2017). When supplemented in utero and in early development, choline has both immediate and long-term beneficial effects in healthy disomic rats and mice (Meck et al, 1988;1989;Loy et al, 1991;Holler et al, 1996;Meck and Williams, 1997;1999;Pyapali et al, 1998;Tees, 1999;Sandstrom et al, 2002;Li et al, 2004;Mellott et al, 2004) and in rodent models of prenatal ethanol exposure, Rett syndrome, and status epilepticus (Holmes et al, 2002;Nag and Berger-Sweeney, 2007;Thomas et al, 2007;Nag et al, 2008;Ward et al, 2008;Thomas et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Maternal Choline Supplementation Alters Basal Forebrain Cholinergic Neuron Gene Expression in the Ts65Dn Mouse Model of Down Syndrome

Kelley

Ginsberg

Alldred

et al. 2019

Developmental Neurobiology

View full text Add to dashboard Cite

Down syndrome (DS), trisomy 21, is marked by intellectual disability and a premature aging profile including degeneration of the basal forebrain cholinergic neuron (BFCN) projection system, similar to Alzheimer's disease (AD). Although data indicate that perinatal maternal choline supplementation (MCS) alters the structure and function of these neurons in the Ts65Dn mouse model of DS and AD (Ts), whether MCS affects the molecular profile of vulnerable BFCNs remains unknown. We investigated the genetic signature of BFCNs obtained from Ts and disomic (2N) offspring of Ts65Dn dams maintained on a MCS diet (Ts+, 2N+) or a choline normal diet (ND) from mating until weaning, then maintained on ND until 4.4–7.5 months of age. Brains were then collected and prepared for choline acetyltransferase (ChAT) immunohistochemistry and laser capture microdissection followed by RNA extraction and custom‐designed microarray analysis. Findings revealed upregulation of select transcripts in classes of genes related to the cytoskeleton (Tubb4b), AD (Cav1), cell death (Bcl2), presynaptic (Syngr1), immediate early (Fosb, Arc), G protein signaling (Gabarap, Rgs10), and cholinergic neurotransmission (Chrnb3) in Ts compared to 2N mice, which were normalized with MCS. Moreover, significant downregulation was seen in select transcripts associated with the cytoskeleton (Dync1h1), intracellular signaling (Itpka, Gng3, and Mlst8), and cell death (Ccng1) in Ts compared to 2N mice that was normalized with MCS. This study provides insight into genotype‐dependent differences and the effects of MCS at the molecular level within a key vulnerable cell type in DS and AD.

show abstract

“…Choline is an essential nutrient which showed neuroprotective effects in both animal and human studies (Blusztajn et al, 2017 ). The synaptogenesis, a process that occurs throughout life, is enhanced by choline supplementation.…”

Section: Discussionmentioning

confidence: 99%

Inside the Developing Brain to Understand Teen Behavior From Rat Models: Metabolic, Structural, and Functional-Connectivity Alterations Among Limbic Structures Across Three Pre-adolescent Stages

Zoratto

Altabella

Tistarelli

et al. 2018

Front. Behav. Neurosci.

View full text Add to dashboard Cite

Adolescence is an age of transition when most brain structures undergo drastic modifications, becoming progressively more interconnected and undergoing several changes from a metabolic and structural viewpoint. In the present study, three MR techniques are used in rats to investigate how metabolites, structures and patterns of connectivity do change. We focused in particular on areas belonging to the limbic system, across three post-weaning developmental stages: from “early” (PND 21–25) to “mid” (i.e., a juvenile transition, PND 28–32) and then to “late” (i.e., the adolescent transition, PND 35–39). The rs-fMRI data, with comparison between early and mid (juvenile transition) age-stage rats, highlights patterns of enhanced connectivity from both Striata to both Hippocampi and from there to (left-sided) Nucleus accumbens (NAcc) and Orbitofrontal Cortex (OFC). Also, during this week there is a maturation of pathways from right Striatum to ipsilateral NAcc, from right OFC to ipsilateral NAcc and vice versa, from left Prefrontal Cortex to ipsilateral OFC and eventually from left Striatum, NAcc and Prefrontal Cortex to contralateral OFC. After only 1 week, in late age-stage rats entering into adolescence, the first pathway mentioned above keeps on growing while other patterns appear: both NAcc are reached from contralateral Striatum, right Hippocampus from both Amygdalae, and left NAcc -further- from right Hippocampus. It's interesting to notice the fact that, independently from the age when these connections develop, Striata of both hemispheres send axons to both Hippocampi and both NAcc sides, both Hippocampi reach left NAcc and OFC and finally both NAcc sides reach right OFC. Intriguingly, the Striatum only indirectly reaches the OFC by passing through Hippocampus and NAcc. Data obtained with DTI highlight how adolescents' neurite density may be affected within sub-cortical gray matter, especially for NAcc and OFC at “late” age-stage (adolescence). Finally, levels of metabolites were investigated by 1H-MRS in the anterior part of the hippocampus: we put into evidence an increase in myo-inositol during juvenile transition and a taurine reduction plus a total choline increase during adolescent transition. In this paper, the aforementioned pattern guides the formulation of hypotheses concerning the correlation between the establishment of novel brain connections and the emergence of behavioral traits that are typical of adolescence.

show abstract

Neuroprotective Actions of Dietary Choline

Cited by 187 publications

References 233 publications

Aberrant cardiolipin metabolism is associated with cognitive deficiency and hippocampal alteration in tafazzin knockdown mice

Aberrant cardiolipin metabolism is associated with cognitive deficiency and hippocampal alteration in tafazzin knockdown mice

Maternal Choline Supplementation Alters Basal Forebrain Cholinergic Neuron Gene Expression in the Ts65Dn Mouse Model of Down Syndrome

Inside the Developing Brain to Understand Teen Behavior From Rat Models: Metabolic, Structural, and Functional-Connectivity Alterations Among Limbic Structures Across Three Pre-adolescent Stages

Contact Info

Product

Resources

About