New insight in expression, transport, and secretion of brain-derived neurotrophic factor: Implications in brain-related diseases

Table 1 Implications of BDNF in brain-related diseases

BDNF expression levels in brain diseases andanimal models	Possible involvement of BDNF in therapies
Alzheimer’s disease (patients)
Decreased expression levels of BDNF mRNA
Hippocampus: ref.[147,148]
Cortex: ref.[148,149]
Decreased expression levels of BDNF protein
Serum: ref.[152]
Hippocampus: ref.[150]
Cortex: ref.[150,151]; no change ref.[247]
Alzheimer’s disease (animal models)	Alzheimer’s disease (animal models)
Decreased expression levels of BDNF mRNA	BDNF gene delivery ameliorated age-related cognitive impairment in aged primates and rats. ref.[153]
Cortex: Aβ transgenic strains	7, 8-DHF improved memory deficits in 5XFAD transgenic mouse. ref.[156]
(APPNLh and TgCRND8) ref.[155]
Decreased expression levels of BDNF protein
Hippocumpus: 5XFAD transgenic mouse ref.[156]
Huntington disease (patients)
Decreased expression levels of BDNF mRNA
Serum: ref.[165]
Cortex: ref.[162]
Caudate: decreased TrkB mRNA ref.[162]
Decreased expression levels of BDNF protein
Cortex: ref.[163,165]
Striatum: ref.[163]
Cerebellum: ref.[163]
Substantia nigra: ref.[163]
Caudate and Putamen: ref.[164]
Huntington disease (animal models)	Huntington disease (animal models)
Decreased expression levels of BDNF mRNA	BDNF overexpression improved motor function in R6/2 mice. ref.[167]
Cortex: R6/2 mice, ref.[166,167]	BDNF overexpression ameliorated YAC128 mice phenotype. ref.[168]
Decreased expression levels of BDNF protein	Environmental enrichment-increased BDNF improved the phenotype in R6/1 mice. ref.[169]
Striatum: YAC128 mice, ref.[168];	Sertraline-increased BDNF improved the phenotype in R6/2 mice. ref.[170]
R6/1 mice ref.[169]	7, 8-DHF or 4’-DMA-7,8-DHF improved motor deficits in N171-82Q mice. ref.[171]
Depression (patients)	Depression (patients)
Decreased expression levels of BDNF mRNA	Antidepressants increased BDNF in serum. ref.[191-193,248]
Hippocampus: ref.[185] (suicidal)	Antidepressants increased BDNF and TrkB in the cerebellum. ref.[194]
Cortex: ref.[185] (suicidal),
decreased TrkB mRNA ref.[188]
Amygdala: ref.[187]
Decreased expression levels of BDNF protein
Serum: ref.[189-191]
Hippocampus ref.[185] (suicidal)[186] (suicidal)
Cortex: ref.[185] (suicidal)[186] (suicidal)
Depression (animal models)	Depression (animal models)
Decreased expression levels of BDNF mRNA	Antidepressants increased BDNF in the rat brain
Hippocampus: social defeat stress, ref.[195];	Tricyclic antidepressants (TCA; including imipramine, desipramine), ref.[202-204]
restrain stress, ref.[196,197] (also TrkB);	Selective serotonin reuptake inhibitors (SSRI; fluoxetine, paroxetine, sertraline), ref.[202,204-206,251]
maternal deprivation, ref.[198];	Noradrenergic and specific serotonergic antidepressants (NaSSA; mirtazapine, mianserin), ref.[202,207]
dexamethasone, ref.[199];	Monoamine oxidase inhibitors (MAOIs; tranylcypromine), ref.[202-204]
corticosterone, ref.[196,200,201];
foot shock stress, ref.[249]
Cortex: social defeat stress, ref.[195];	Electroconvulsive seizures induced BDNF expression. ref.[202,208-211]
maternal deprivation, ref.[198];	7,8-DHF showed an antidepressant-like effect. ref.[212]
dexamethasone, ref.[199];	Direct BDNF infusion into the rat midbrain induced antidepressant-like effects. ref.[213]
cold swim stress, ref.[250]
Amygdala: social defeat stress, ref.[193]
Decreased expression levels of BDNF protein
Hippocampus: maternal deprivation, ref.[198];
corticosterone, ref.[200,201];
cold swim stress, ref.[250]
Schizophrenia (patients)	Schizophrenia (patients)
Decreased expression levels of BDNF mRNA	Clozapine treatment increased serum BDNF mRNA levels. ref.[235,236]
Serum: ref.[236,252];
decreased TrkB mRNA ref.[253]
Cortex: ref.[122,233,254,255];
decreased TrkB mRNA ref.[255];
incrased trunkated TrkB mRNA ref.[256]
Serum: ref.[235,257-260]
Hippocampus: ref.[231];
abnormal expression of TrkB ref.[261];
increased BDNF mRNA ref.[230]
Cortex: ref.[232-234];
increase BDNF mRNA ref.[230,231]
Cerebrospinal fluid ref.[234]
Schizophrenia (animal models)	Schizophrenia (animal models)
Decreased expression levels of BDNF mRNA	Mk-801-induced decline in hippocampal BDNF mRNA was normalized by olanzapine, but exacerbated by haloperidol. ref.[238]
Hippoaumpus: phencyclidine, ref.[238];	Haloperidol or risperidone decreased BDNF protein in the rat frontal cortex and hippocampus. ref.[241]
MK-801 ref.[239];	Haloperidol decreased BDNF and TrkB protein in the rat hippocampus. ref.[242]
ibotenic acid lesions, ref.[240]	Risperidon, olanzapine, haloperidol, and chlorpromazine decreased BDNF levels in the rat striatum and hippocampus. ref.[243]
Cortex: phencyclidine, ref.[238]	Haloperidol down-regulated BDNF mRNA expression in the rat hippocampus. ref.[262]
Amygdala: phencyclidine, ref.[238]

BDNF: Brain-derived neurotrophic factor.