Longitudinal tracing of neurochemical metabolic disorders in working memory neural circuit and optogenetics modulation in rats with vascular cognitive impairment
Section snippets
Background
Chronic cerebral ischemia is a very common brain disease in middle-aged and elderly people, usually triggered by vascular disorders, thrombosis, or cardiac functions weaken (Iadecola et al., 2019), which occurs hypoperfusion of brain blood flow unable to meet metabolic demand, limits oxygen and other nutrients supply and leads to the necrosis of brain tissue, cerebral atrophy or cerebral infarction, often involving cortical and subcortical important brain areas (Jellinger, 2008; Yang et al.,
Animal ethics and experimental design
Thirty-one male Sprague-Dawley rats (8-week-old, weighing 250−300 g) were purchased from Shanghai SLAC Laboratory Animal Co., Ltd. (Shanghai, China). Experimental animals are raised by the Experimental Animal Center of Fujian University of Traditional Chinese Medicine [license number: SYXK (Min) 2019-0007]. Rats were reared on a 12 -h light/12 -h dark cycle and provided with food and water. All experimental procedures are strictly in accordance with the International Ethical Guidelines and the
Magnetic resonance angiography of bilateral common carotid arteries in rats with chronic cerebral ischemia
To identify whether the successful of the 2-VO model of chronic cerebral ischemia, 3D TOF MR angiography was used to detect the diameter of bilateral common carotid arteries at 24 h after 2-VO operation. Compared with the sham group, the bilateral common carotid arteries of the 2-VO model rats were obviously blocked, and there were new small vessels, suggesting that the rat model of chronic cerebral ischemia was successfully established (Supplementary Fig. S5).
Longitudinal tracking of neurochemicals and metabolism in the working memory neural circuit of rats with chronic cerebral ischemia
To explore the time course changes
Discussion
In this study, the longitudinal experimental design was performed to track the pathological process of rats with chronic cerebral ischemia. 1H-MRS was applied to detect the dynamic changes of neurochemicals and metabolism in working memory neural circuit following chronic cerebral ischemia. The results showed that the concentration of NAA in the right hippocampus, left hippocampus, right mPFC and mediodorsal thalamus were initially decreased at 7 days after chronic cerebral ischemia, and GABA
Conclusion
To sum up, in vivo 1H-MRS is a promising tool for longitudinal tracing of neurochemicals and metabolism in the brain. The study revealed that neurochemical metabolism was impaired in working memory neural circuit of hippocampus-mediodorsal thalamus-mPFC as early as 1∼4 weeks after chronic cerebral ischemia and demonstrated that optogenetics modulation of PV neurons in the mPFC can improve the pathological changes and enhance working memory, which provides a theoretical and experimental basis
Ethical approval and consent to participate
Experimental animals are raised by the Experimental Animal Center of Fujian University of Traditional Chinese Medicine [license number: SYXK (Min) 2019-0007]. All experimental procedures are strictly in accordance with the International Ethical Guidelines and the National Institutes of Health Guide for the Care and Use of Laboratory Animals, and were approved by the Ethics Committee of Fujian University of Traditional Chinese Medicine.
Consent for publication
All authors have read the manuscript and indicated consent for publication.
Authors' contributions
W.L.L., H.W.L. and T.T.J. contributed to the experimental design. H.W.L., S.X.L. and M.G.Y. contributed to the 1H-MRS scans and data analysis. T.T.J. and H.W.L. contributed to the optogenetics modulation of PV neurons for VCI. W.L.L., H.W.L., T.T.J., L.W.C., Y.L.D. and W.W.J. contributed to most of the data collection, discussion, and interpretation. All authors read and approved the final manuscript.
Funding
This study was supported by grants from the National Natural Science Foundation of China (Grant No. 81873355) and the Science and Technology platform construction project of Fujian Science and Technology Department (Grant No. 2018Y2002).
Declaration of Competing Interest
The authors declare that they have no conflict of interest.
References (89)
- et al.
Cholinergic circuitry functioning in patients with vascular cognitive impairment—no dementia
Brain Stimul.
(2016) - et al.
Neuronal pathology in the hippocampal area of patients with bipolar disorder: a study with proton magnetic resonance spectroscopic imaging
Biol. Psychiatry
(2003) - et al.
Inhibitory and excitatory mechanisms in the human cingulate-cortex support reinforcement learning: a functional Proton Magnetic Resonance Spectroscopy study
Neuroimage
(2019) - et al.
Permanent, bilateral common carotid artery occlusion in the rat: a model for chronic cerebral hypoperfusion-related neurodegenerative diseases
Brain Res. Rev.
(2007) - et al.
Pathophysiological rat model of vascular dementia: magnetic resonance spectroscopy, microimaging and behavioral study
Brain Res.
(2014) - et al.
Differences in the metabolism of inositol and phosphoinositides by cultured cells of neuronal and glial origin
Biochim. Biophys. Acta
(1989) Cellular basis of working memory
Neuron
(1995)- et al.
Prevalence of dementia subtypes in United States Medicare fee-for-service beneficiaries, 2011–2013
Alzheimer’s Dement.
(2017) - et al.
Hypoxia regulates the level of glutamic acid decarboxylase enzymes and interrupts inhibitory synapse stability in primary cultured neurons
Neurotoxicology
(2018) - et al.
Vascular cognitive impairment and dementia: JACC scientific expert panel
J. Am. Coll. Cardiol.
(2019)
1H magnetic resonance spectroscopic imaging of permanent focal cerebral ischemia in rat: longitudinal metabolic changes in ischemic core and rim
Brain Res.
Spectroscopic markers of memory impairment, symptom severity and age of onset in older people with lifetime depression: discrete roles of N-acetyl aspartate and glutamate
J. Affect. Disord.
Morphologic diagnosis of “vascular dementia” - a critical update
J. Neurol. Sci.
Neurochemical profiles in hereditary ataxias: a meta-analysis of Magnetic Resonance Spectroscopy studies
Neurosci. Biobehav. Rev.
An ultrastructural study of the neural circuit between the prefrontal cortex and the mediodorsal nucleus of the thalamus
Prog. Neurobiol.
Arginine vasopressin attenuates dysfunction of hippocampal theta and gamma oscillations in chronic cerebral hypoperfusion via V1a receptor
Brain Res. Bull.
Longitudinal tracing of white matter integrity on diffusion tensor imaging in the chronic cerebral ischemia and acute cerebral ischemia
Brain Res. Bull.
The mediodorsal thalamus: an essential partner of the prefrontal cortex for cognition
Biol. Psychiatry
Concentration-response relationship of the alpha7 nicotinic acetylcholine receptor agonist FRM-17874 across multiple in vitro and in vivo assays
Biochem. Pharmacol.
Models and mechanisms of vascular dementia
Exp. Neurol.
The impact of cerebrovascular aging on vascular cognitive impairment and dementia
Ageing Res. Rev.
Prefrontal cortical GABA modulation of spatial reference and working memory
Int. J. Neuropsychopharmacol.
Kinetic differences between the isoforms of glutamate decarboxylase: implications for the regulation of GABA synthesis
J. Neurochem.
Thalamic projections sustain prefrontal activity during working memory maintenance
Nat. Neurosci.
Cerebral metabolism in man after acute stroke: new observations using localized proton NMR spectroscopy
Magn. Reson. Med.
Neuronal oscillations in cortical networks
Science
Driving fast-spiking cells induces gamma rhythm and controls sensory responses
Nature
Hydrogen proton magnetic resonance spectroscopy in multidomain amnestic mild cognitive impairment and vascular cognitive impairment without dementia
Am. J. Alzheimers Dis. Other Demen.
The cognitive neuroscience of working memory
Annu. Rev. Psychol.
Optogenetics
Nat. Methods
Next-generation optical technologies for illuminating genetically targeted brain circuits
J. Neurosci.
N-acetylaspartate: a literature review of animal research on brain ischaemia
J. Neurochem.
Vascular cognitive impairment
Circ. Res.
The nucleus reuniens of the thalamus sits at the nexus of a hippocampus and medial prefrontal cortex circuit enabling memory and behavior
Learn. Mem.
Prefrontal-hippocampal interactions in episodic memory
Nat. Rev. Neurosci.
Comparative localization of two forms of glutamic acid decarboxylase and their mRNAs in rat brain supports the concept of functional differences between the forms
J. Neurosci.
PV interneurons: critical regulators of E/I balance for prefrontal cortex-dependent behavior and psychiatric disorders
Front. Neural Circuits
PV interneurons: critical regulators of E/I balance for prefrontal cortex-dependent behavior and psychiatric disorders
Front. Neural Circuits
Layer-dependent activity in human prefrontal cortex during working memory
Nat. Neurosci.
1H-MR spectroscopy metabolite levels correlate with executive function in vascular cognitive impairment
J. Neurol Neurosurg. Psychiatry
Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the american heart association/american stroke association
Stroke
Molecular neuroimaging in vascular cognitive impairment
Stroke
dl-3-n-butylphthalide preserves white matter integrity and alleviates cognitive impairment in mice with chronic cerebral hypoperfusion
CNS Neurosci. Ther.
Neurochemical changes in the hippocampus and prefrontal cortex associated with electroacupuncture for learning and memory impairment
Int. J. Mol. Med.
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These authors contributed equally to this article.