Table 3.

Role of BDNF in Huntington’s disease.

Observations		References
Huntington’s disease patients
BDNF levels were significantly reduced in brainstem regions containing cardiovascular nuclei. Central administration of BDNF restored the heart rate to control levels.		[101]
In silico prediction and reporter systems prove that levels of BDNF, a central node in the miRNA-mRNA regulatory network, can be post-transcriptionally controlled by upregulated miR-10b-5p and miR-30a-5p. Reduced BDNF expression is associated with neuronal dysfunction and death in Huntington’s disease.		[102]
Huntington’s disease patients exhibited moderately increased intra-platelet BDNF levels and significantly reduced cognitive/emotional abilities. However, platelet BDNF and serotonin (5-HT) transporter (SERT) did not specifically underlie psychosocial deficits in stage-II- Huntington’s disease.		[103]
The BDNF protein levels are decreased in saliva while BDNF-promoter methylation is increased in the blood in Huntington’s disease subjects when compared to controls. Salivary BDNF measures may represent an early marker of disease onset and DNA methylation at the BDNF promoter IV could be a biomarker of psychiatric symptoms in Huntington’s disease patients.		[104]
The BDNF level was significantly lower in Huntington’s disease patients compared to the control; however, there was no correlation between the BDNF level and motor symptoms or cognitive impairment.		[105]
The pathogenesis of Huntington’s disease involved low BDNF expression, potentially mediated by the cAMP, MAPK, and Ras signaling pathways.		[107]
Animal model
R6/2 transgenic mouse model	There is an age-dependent decrease in BDNF expression in the major sources of the afferents to the striatum. BDNF mRNA is progressively reduced in the cerebral cortexes and subcortical sources of striatal afferents, including inputs from the thalamus and the midbrain. The loss of BDNF plays an important role in motor and nonmotor abnormalities in Huntington’s disease and contributes to striatal neurodegeneration.	[96]
zQ175/zQ175|BDNF-HA/BDNF-HA mice	There is a significant decrease in mBDNF–TrkB signaling, but no induction of proBDNF-p75NTR signaling, in the striatal neurons of zQ175 mice, suggesting that the maturation of proBDNF to mBDNF remains intact. The local induction of p75NTR and sortilin is found in immature striatal oligodendrocytes and is associated with severe myelin deficits in the striata of aged zQ175 mice.	[97]
R6/2 transgenic mouse model	Striatal neurons exhibited a blunted trophic response to BDNF that was associated with the decreased activation of the TrkB-Erk1/2 signaling pathway.	[99]
zQ175 mice	There is a significant decrease in BDNF release in the cortical neurons, in the BDNF levels in the striatum, and in the total travel length and speed of BDNF-containing vesicles in the neurons.	[100]
N171-82Q mice	The BDNF levels were significantly reduced in the brainstem regions containing cardiovascular nuclei. The central administration of BDNF restored the heart rate to control levels.	[101]
Emx1-Cre/Q140 or Emx1-Cre/Q175 heterozygote mouse model	The full-fusion and partial-fusion modes of BDNF-containing vesicles were significantly altered after the onset of Huntington’s disease symptoms. The development of Huntington’s disease is reinforcedby abnormal BDNF transcription, transport, and cortical axonal secretion in the striatum.	[106]
Wild-type and age-matched symptomatic R6/2 mice	BDNF exerts neuroprotective effects on NMDA-dependent toxicity, these effects of BDNF seem specifically related to the pathological genotype, and they require endogenous A2AR activation.	[108]
R6/2-BDNF Huntington’s disease transgene mice	BDNF supplementation in vivo can enhance the survival and development of adult subventricular-zone-derived cells that divert to the striatum; however, augmenting BDNF levels within the olfactory bulb does not substantially improve the survival of adult-born GABAergic granule cells (GCs) in R6/2 mice at late disease stages.	[109]
3-nitropropionic acid mice model	BDNF and neurotrophin-4/5 (NT-4/5) elicit an antagonistic or synergistic effect that depends on the activation of the truncated isoform or the stimulation of the full-length isoform of the tropomyosin receptor kinase B.	[110]
Cell culture
Huntington’s disease mutant knock-in and wild-type striatal cells	Huntington’s disease cells released lower levels of pro- and mature-BDNF. BDNF-mCherry overexpression rescued the decreased AKT phosphorylation, reduced the caspase-3 activation, and enhanced the activated ERK observed in Huntington’s disease cells.	[98]
OS-7 cell culture	BDNF and neurotrophin-4/5 (NT-4/5) elicit an antagonistic or synergistic effect that depends on the activation of the truncated isoform or the stimulation of the full-length isoform of the tropomyosin receptor kinase B.	[110]