Understanding the multifactorial nature of cognitive decline associated with dementia

 

Neurodegenerative disorders are defined by neuronal loss and often associated with dementia. Understanding the multifactorial nature of cognitive decline is of particular interest. Cell loss is certainly a possibility but also an early imbalance in the complex gene networks involved in learning and memory. The small (~ 22 nt) non-coding microRNAs play a major role in gene expression regulation and have been linked to neuronal survival and cognition. Interestingly, changes in microRNA signatures are associated with neurodegenerative disorders. In this review, we explore the role of three microRNAs, namely miR-132, miR-124 and miR-34, which are dysregulated in major neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. Interestingly, these microRNAs have been associated with both memory impairment and neuronal survival, providing a potential common molecular mechanism contributing to dementia.

	Neuropathology	Regulation	Reported finding	Techniques	References
miR-132	AD	Down	Human hippocampus, prefrontal cortex and temporal gyrus of LOAD patients	nCounter system, deep-sequencing and qRT-PCR	Lau et al. (2013)
		Down	Human hippocampus, medial frontal gyrus and cerebellum of LOAD patients	qRT-PCR	Cogswell et al. (2008)
		Down	Human temporal cortex of load patients	Multiplex qRT-PCR and qRT-PCR	Wong et al. (2013)
		Down	Human temporal cortex of load patients	Deep-sequencing and qRT-PCR	Hebert et al. (2013)
		Down	human hippocampus, frontal lobe and temporal lobe of LOAD patients	qRT-PCR	Smith et al. (2015)
	MCI	Down	Human temporal lobe of MCI patients	qRT-PCR	Smith et al. (2015)
		Down	Human frontal cortex of MCI patients	Microarray (Exiqon miRCURY LNA) and qRT-PCR	Weinberg et al. (2015)
		Down	Human serum of MCI patients	qRT-PCR	Xie et al. (2015)
	PD	Down	Brainstem area of alpha-synuclein (A30P)-transgenic mouse	LC Sciences microfluidic chip technology	Gillardon et al. (2008)
		Up	Mesencephalic brain areas of Berlin-Druckrey IV rat affected	Microarray (Chip ID miRRat 19.0 version) and qRT-PCR	Lungu et al. (2013)
		Up	Human laser microdissected dopamine neurons of PD patients	Human MicroRNA TaqMan® Arrays A 2.0	Briggs et al. (2015)
		Down	Human prefrontal cortex Brodmann Area 9 of HD patients	small RNA-sequencing	Hoss et al. (2016)
	HD	Down	Striatum of YAC128 and R6/2 transgenic mouse	Agilent Mouse miRNA Microarray and qRT-PCR	Lee et al. (2011)
		Down	Human Brodmann area 4 of HD patients and cortex of R6/2 transgenic mouse	qRT-PCR	Johnson et al. (2008)
		Down	Human prefrontal cortex Brodmann Area 9 of HD patients	Small RNA-sequencing	Hoss et al. (2015)
		Up	Human Brodmann area 4 of HD patients	qRT-PCR	Packer et al. (2008)
miR-124	AD	Down	Human hippocampus of LOAD patients	nCounter system	Lau et al. (2013)
	PD	Down	Substantia nigra of MPTP-induced PD mouse model	qRT-PCR and in situ hybridization	Kanagaraj et al. (2014)
		Down	Dopaminergic neurons within the substantia nigra of MPTP-induced PD mouse	qRT-PCR and in situ hybridization	Wang et al. (2015)
	HD	Down	Cortex of R6/2 transgenic mouse model	qRT-PCR	Johnson et al. (2008)
		Down	Human Brodmann area 4 of HD patients	qRT-PCR	Packer et al. (2008)
		Down	Human frontal cortex and striatum of HD patients	Deep sequencing and Agilent Human miRNA microarrays	Marti et al. (2010)
miR-34a	AD	Up	Human hippocampus, medial frontal gyrus and cerebellum of LOAD patients	RT-qPCR	Cogswell et al. (2008)
		Up	Cortex of APPswe/PSΔE9 transgenic mouse	Dual-channel microarray μParaflo™ microfluidics chips	Wang et al. (2009)
		Up	Human blood mononuclear cells of LOAD patients	Human microRNA microarray (MMChip)	Schipper et al. (2007)
miR-34b	HD	Up	Mutant-HTT-transfected NT2 cell model and human plasma of HD patients	miRCURY LNA miR v 11.0 arrays and miRNA RT-PCR	Gaughwin et al. (2011)
		Up	Striatum of YAC128 and R6/2 transgenic mouse model	Agilent Mouse miRNA Microarray	Lee et al. (2011)
miR-34b/c	PD	Down	Human amygdala, frontal cortex, substantia nigra and cerebellum of PD patients	miRCURY™ array (Exiqon) and miRNA RT-PCR	Minones-Moyano et al. (2011)
miR-34c	AD	Up	Hippocampus of AD APPPS1–21 mouse and human hippocampus of LOAD patients	Small RNA massive parallel sequencing and qRT-PCR	Zovoilis et al. (2011)

 

 

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Reference

Hernandez-Rapp J, Rainone S, Hébert Sb. (2016) MicroRNAs underlying memory deficits in neurodegenerative disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry S0278-5846(16), 30057-4. [abstract]