Imaging mitochondrial motility within live hippocampal neurons

alterations due to amyloid-β, hyperglycaemia or in vitro aging

Susan Chalmers, Rachael Rooney, Sumaya Al-Bazi, Christina Mexi, Christopher D. Saunter

Research output: Contribution to conferencePoster

Abstract

Appropriate mitochondrial activity plays a vital role in neuronal function, from efficient ATP provision to localised Ca2+-buffering that modulates synaptic activity. Mitochondrial dysfunction is associated with many neurodegenerative diseases. Ca2+ overload disrupts mitochondrial integrity, disabling ATP production, releasing accumulated Ca2+ and disrupting redox/antioxidant balance, contributing to neuronal death. Chronically-neurotoxic environments (such as a build-up of the Alzheimer’s-associated amyloid-β peptide or hyperglycaemia) may disrupt mitochondrial turnover or motility, ultimately contributing to cellular decline. Questions remain, as to the temporal sequence, interplay and relative importance of such changes in mitochondrial physiology to neurodegeneration.
Using epifluorescence imaging of primary hippocampal cells, we showed that chronic exposure to amyloid-β1-42 (500 nM, 1 h), decreased mitochondrial motility with no gross change in mitochondrial morphology or membrane potential. Acutely switching mature neurons (3 weeks in vitro) from the commonly-used supra-physiological glucose media (25 mM) into physiological glucose (3 mM) increased mitochondrial motility; whereas immature neurons (1 week) displayed the same, high level of mitochondrial motility in either hyperglycaemic or physiological glucose. Repeatedly imaging the same individual cells throughout in vitro maturation revealed a decrease in mitochondrial motility plus shift in morphology: from a heterogeneous population containing many branched and extended mitochondria (≥20 μm) in young neurons, towards a more-homogeneous population largely comprising small organelles dispersed along processes. These results indicate that an inhibition of mitochondrial motility may be an early event preceding Alzheimer’s-associated neurodegeneration, which may also be exacerbated by diabetic-like hyperglycaemia but may also be influenced, or indeed masked, by differences in cell age.
Original languageEnglish
Publication statusPublished - 22 Aug 2018
EventGlasgow Imaging Network 2018 - University of Glasgow, Glasgow, United Kingdom
Duration: 22 Aug 201822 Aug 2018

Conference

ConferenceGlasgow Imaging Network 2018
Abbreviated titleGIN2018
CountryUnited Kingdom
CityGlasgow
Period22/08/1822/08/18

Fingerprint

Amyloid
Hyperglycemia
Neurons
Glucose
Adenosine Triphosphate
Mitochondrial Turnover
Neurodegenerative Diseases
Organelles
Membrane Potentials
Population
Oxidation-Reduction
Mitochondria
Antioxidants
Peptides
In Vitro Techniques

Keywords

  • imaging
  • mitochondrial mobility
  • hippocampal neurons

Cite this

Chalmers, S., Rooney, R., Al-Bazi, S., Mexi, C., & Saunter, C. D. (2018). Imaging mitochondrial motility within live hippocampal neurons: alterations due to amyloid-β, hyperglycaemia or in vitro aging. Poster session presented at Glasgow Imaging Network 2018, Glasgow, United Kingdom.
Chalmers, Susan ; Rooney, Rachael ; Al-Bazi, Sumaya ; Mexi, Christina ; Saunter, Christopher D. / Imaging mitochondrial motility within live hippocampal neurons : alterations due to amyloid-β, hyperglycaemia or in vitro aging. Poster session presented at Glasgow Imaging Network 2018, Glasgow, United Kingdom.
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Chalmers, S, Rooney, R, Al-Bazi, S, Mexi, C & Saunter, CD 2018, 'Imaging mitochondrial motility within live hippocampal neurons: alterations due to amyloid-β, hyperglycaemia or in vitro aging' Glasgow Imaging Network 2018, Glasgow, United Kingdom, 22/08/18 - 22/08/18, .

Imaging mitochondrial motility within live hippocampal neurons : alterations due to amyloid-β, hyperglycaemia or in vitro aging. / Chalmers, Susan; Rooney, Rachael; Al-Bazi, Sumaya; Mexi, Christina; Saunter, Christopher D.

2018. Poster session presented at Glasgow Imaging Network 2018, Glasgow, United Kingdom.

Research output: Contribution to conferencePoster

TY - CONF

T1 - Imaging mitochondrial motility within live hippocampal neurons

T2 - alterations due to amyloid-β, hyperglycaemia or in vitro aging

AU - Chalmers, Susan

AU - Rooney, Rachael

AU - Al-Bazi, Sumaya

AU - Mexi, Christina

AU - Saunter, Christopher D.

PY - 2018/8/22

Y1 - 2018/8/22

N2 - Appropriate mitochondrial activity plays a vital role in neuronal function, from efficient ATP provision to localised Ca2+-buffering that modulates synaptic activity. Mitochondrial dysfunction is associated with many neurodegenerative diseases. Ca2+ overload disrupts mitochondrial integrity, disabling ATP production, releasing accumulated Ca2+ and disrupting redox/antioxidant balance, contributing to neuronal death. Chronically-neurotoxic environments (such as a build-up of the Alzheimer’s-associated amyloid-β peptide or hyperglycaemia) may disrupt mitochondrial turnover or motility, ultimately contributing to cellular decline. Questions remain, as to the temporal sequence, interplay and relative importance of such changes in mitochondrial physiology to neurodegeneration.Using epifluorescence imaging of primary hippocampal cells, we showed that chronic exposure to amyloid-β1-42 (500 nM, 1 h), decreased mitochondrial motility with no gross change in mitochondrial morphology or membrane potential. Acutely switching mature neurons (3 weeks in vitro) from the commonly-used supra-physiological glucose media (25 mM) into physiological glucose (3 mM) increased mitochondrial motility; whereas immature neurons (1 week) displayed the same, high level of mitochondrial motility in either hyperglycaemic or physiological glucose. Repeatedly imaging the same individual cells throughout in vitro maturation revealed a decrease in mitochondrial motility plus shift in morphology: from a heterogeneous population containing many branched and extended mitochondria (≥20 μm) in young neurons, towards a more-homogeneous population largely comprising small organelles dispersed along processes. These results indicate that an inhibition of mitochondrial motility may be an early event preceding Alzheimer’s-associated neurodegeneration, which may also be exacerbated by diabetic-like hyperglycaemia but may also be influenced, or indeed masked, by differences in cell age.

AB - Appropriate mitochondrial activity plays a vital role in neuronal function, from efficient ATP provision to localised Ca2+-buffering that modulates synaptic activity. Mitochondrial dysfunction is associated with many neurodegenerative diseases. Ca2+ overload disrupts mitochondrial integrity, disabling ATP production, releasing accumulated Ca2+ and disrupting redox/antioxidant balance, contributing to neuronal death. Chronically-neurotoxic environments (such as a build-up of the Alzheimer’s-associated amyloid-β peptide or hyperglycaemia) may disrupt mitochondrial turnover or motility, ultimately contributing to cellular decline. Questions remain, as to the temporal sequence, interplay and relative importance of such changes in mitochondrial physiology to neurodegeneration.Using epifluorescence imaging of primary hippocampal cells, we showed that chronic exposure to amyloid-β1-42 (500 nM, 1 h), decreased mitochondrial motility with no gross change in mitochondrial morphology or membrane potential. Acutely switching mature neurons (3 weeks in vitro) from the commonly-used supra-physiological glucose media (25 mM) into physiological glucose (3 mM) increased mitochondrial motility; whereas immature neurons (1 week) displayed the same, high level of mitochondrial motility in either hyperglycaemic or physiological glucose. Repeatedly imaging the same individual cells throughout in vitro maturation revealed a decrease in mitochondrial motility plus shift in morphology: from a heterogeneous population containing many branched and extended mitochondria (≥20 μm) in young neurons, towards a more-homogeneous population largely comprising small organelles dispersed along processes. These results indicate that an inhibition of mitochondrial motility may be an early event preceding Alzheimer’s-associated neurodegeneration, which may also be exacerbated by diabetic-like hyperglycaemia but may also be influenced, or indeed masked, by differences in cell age.

KW - imaging

KW - mitochondrial mobility

KW - hippocampal neurons

M3 - Poster

ER -

Chalmers S, Rooney R, Al-Bazi S, Mexi C, Saunter CD. Imaging mitochondrial motility within live hippocampal neurons: alterations due to amyloid-β, hyperglycaemia or in vitro aging. 2018. Poster session presented at Glasgow Imaging Network 2018, Glasgow, United Kingdom.