Mitochondria controlled by UCP2 determine hypoxia-induced synaptic remodeling in the cortex and hippocampus

Neurobiology of Disease
Luis VarelaTamas L Horvath

Abstract

We have established that mitochondrial dynamics, under metabolic control, play crucial roles in the regulation of systemic metabolism by hypothalamic circuits. The role of mitochondrial dynamics in neurons in higher brain regions is, however, ill-defined. Here we show that early postnatal exposure of animals to temporal hypoxia followed by normoxia, a major metabolic challenge on brain cells, resulted in adaptive responses of neuronal mitochondria. The number and oxygen consumption of mitochondria in cortical and hippocampal neurons were altered, while mitochondria-endoplasmic reticulum (ER) interactions were preserved. These changes coincided with increased synaptic input of neurons in the cortex and hippocampus. We identified that the changing oxygen tension triggered mitochondrial uncoupling protein 2 (UCP2) expression and showed that UCP2 is crucial for these adaptive mitochondrial responses. In UCP2 KO mice, changing oxygen tension did not induce changes in mitochondrial parameters and function but decreased mitochondria-ER contacts and resulted in loss of synapses both in the cortex and hippocampus. These observations establish that mitochondrial location controlled by UCP2 is relevant for adaptive responses of neurons in...Continue Reading

References

Oct 1, 1988·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·H J GundersenB Pakkenberg
Oct 1, 1986·Physiology & Behavior·J P Kroon, A L Riley
Jun 20, 1997·Brain Research·W B StewartM Schwartz
Dec 31, 1997·Pediatrics·R C Vannucci, J M Perlman
Nov 13, 1998·Current Opinion in Neurobiology·F H Gage
Jul 31, 2002·Biochemical Pharmacology·Ingo BechmannTamas L Horvath
Feb 15, 2003·JAMA : the Journal of the American Medical Association·Laura R MentRobert W Makuch
Feb 21, 2004·Developmental Medicine and Child Neurology·Matthew AllinRobin Murray
Oct 21, 2004·Nature Neuroscience·A Denise R GarciaMichael V Sofroniew
May 27, 2005·Experimental Neurology·Devon M FagelFlora M Vaccarino
Oct 15, 2005·Nature Reviews. Neuroscience·Zane B AndrewsTamas L Horvath
Feb 24, 2006·Nature Neuroscience·Sabrina DianoTamas L Horvath
Feb 28, 2008·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Tomas DeierborgGustav Mattiasson
Oct 17, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Marcelo O DietrichTamas L Horvath
Jan 15, 2009·American Journal of Physiology. Endocrinology and Metabolism·Zane B Andrews, Tamas L Horvath
Jan 30, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Devon M FagelFlora M Vaccarino
Sep 24, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Xin-Hong ZhuTian-Ming Gao
Jun 24, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Baoyuan BiFlora M Vaccarino
Sep 21, 2012·Nature Reviews. Molecular Cell Biology·Ashley A Rowland, Gia K Voeltz
Feb 28, 2013·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Yi-Wei TsaiRay-Yau Wang
Feb 15, 2014·Clinics in Perinatology·Natalina SalmasoFlora M Vaccarino

❮ Previous
Next ❯

Citations

Jul 2, 2016·Mitochondrion·Misa HiroseSaleh M Ibrahim
Mar 7, 2017·Scientific Reports·Estefanía Acaz-FonsecaMariana Astiz
Jan 21, 2018·Antioxidants & Redox Signaling·Petr JežekMartin Jabůrek
Jan 20, 2018·Nature Reviews. Neuroscience·Michael J Devine, Josef T Kittler
Sep 7, 2016·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·John G GeislerMark P Mattson
Mar 17, 2019·Cerebral Cortex·Melissa Taylor-GiorlandoTamas L Horvath
Sep 6, 2020·Genetics, Selection, Evolution : GSE·Seyed Mohammad GhoreishifarArash Javanmard

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.