The Pleiotropic Potential of BDNF beyond Neurons: Implication for a Healthy Mind in a Healthy Body
Abstract
:1. Introduction
2. The Role of BDNF in the Central Control of Energy Balance
Gene | Mutations | Phenotypic Features | Reference |
---|---|---|---|
BDNF | 11p inversion; haploinsufficiency | Severe obesity, hyperphagia, impaired cognitive function, hyperactivity | [19] Gray, J. et al., 2006 [22] Han, J.C., 2016 |
Deletions including the 11p14 BDNF locus among patients with WAGR syndrome; haploinsufficiency | Obesity, hyperphagia, lower levels of serum BDNF | [20] Han, J.C. et al., 2008 [22] Han, J.C., 2016 | |
Intronic SNP: rs12291063 CC genotype | Obesity | [21] Mou, Z. et al., 2015 | |
SNP rs6265 commonly known as G196A => Val66Met | Susceptibility to obesity, several psychiatric conditions including eating disorders | [25] Rosas-Vargas, H. et al., 2011 [26] Vidović, V. et al., 2020 [27] Ieraci, A. et al., 2020 [22] Han, J.C., 2016 | |
Missense mutation E183K | Severe obesity and moderately learning difficulties | [29] Sonoyama, T. et al., 2020 | |
NTRK2 | Missense mutation Y722C | Severe early-onset obesity, hyperphagia, developmental delay | [18] Yeo, G.S.H. et al., 2004 |
Missense mutations: I98V, P660L, T821A | Severe obesity, developmental delay | [23] Gray, J. et al., 2007 | |
Missense mutations: P204H, R691H, R696K, S714F, R715Q, R715W, P831L | Severe obesity, hyperactivity, maladaptive behaviours and impaired short-term memory | [29] Sonoyama, T. et al., 2020 |
3. BDNF in Energy Expenditure
3.1. BDNF in Thermoregulation
3.2. BDNF in Volitional Physical Activity
3.3. BDNF, Mitochondria and the Regulation of Cellular Bioenergetics
4. The Role of BDNF in the Peripheral Control of Energy Balance
5. BNDF Involvement in Neurodegenerative Disorders
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Animal Model | Intervention/Stimuli | Effects | Reference |
---|---|---|---|
Wistar rats | Chronic intraventricular administration of BDNF and NGF | Reduction in weight gain | [13] Lapchak, P.A.; Hefti, F., 1992 |
Long-Evans rats | ICV BDNF infusion (lateral ventricle) | Appetite suppression and weight loss | [14] Pelleymounter, M.A et al., 1995 |
C57BL/KsJ-db/db mice (obese diabetic mice) | BDNF central (ICV) administration | Reduction in blood glucose and increase in pancreatic insulin | [15] Nonomura, T. et al., 2001 |
C57BL/KsJ-db/db mice (obese diabetic mice); streptozotocin-induced type 1 diabetic mice; KK mice (normoglycemic obese mice with impaired glucose tolerance) | BDNF central (ICV) and subcutaneous administration | Antidiabetic effects | [16] Nakagawa, T. et al., 2000 |
BDNF mutant mice (obese BDNF heterozygous mice) | BDNF central administration (third ventricle) | Transient reversion of eating behaviour and obesity | [17] Kernie, S.G. et al., 2000 |
Bdnfklox/klox mice (deficiency in long 3′ UTR Bdnf mRNA/severe obesity development) | Viral expression of long 3′UTR Bdnf mRNA in the hypothalamus (VMH) | Complete rescue of hyperphagic obesity | [32] Liao, G.-Y. et al., 2012 |
Wild-type mice | Intraperitoneal and ICV administration of glucose after 48h fasting period | Increase in BDNF and TrkB mRNA in VMH | [34] Unger, T.J. et al., 2007 |
BDNF central administration (third ventricle) | Neurons activation in hypothalamic appetite-regulating centers | ||
Bdnf 2L/2L mice | Selectively deletion (viral-mediated) of BDNF alleles in the VMH and DMH | Hyperphagic behavior and obesity | |
C57BL/6J mice | ICV leptin administration | Increase in BDNF mRNA in the dorsomedial part of VMH | [35] Komori, T. et al., 2006 |
Wild-type mice | Injection of a MC4R agonist (MTII) into the dorsal third ventricle after a 44 h fasting period | Increase in BDNF mRNA in the VMH | [36] Xu, B. et al., 2003 |
Wistar Han rats | Intraparenchymal infusion of BDNF in the DVC | Anorexia and weight loss | [38] Bariohay, B. et al., 2005 |
Peripheral leptin injection | Increase in BDNF protein content within the DVC | ||
Wistar Han rats | BDNF ICV injection into the DVC (4th ventricle) | Reduction in food intake | [39] Bariohay, B. et al., 2009 |
ICV delivery of a MC3/4R agonist (MTII) into the DVC (4th ventricle) | Increase in the BDNF protein content in the DVC | ||
ICV delivery of a MC3/4R antagonist (SHU9119) into the DVC (4th ventricle) | Decrease in the BDNF protein content in the DVC | ||
Sprague-Dawley rats | ICV (4th ventricle/hindbrain) BDNF injection | Reduction in cumulative food intake and body weight; increase in core temperature | [40] Spaeth, A.M. et al., 2012 |
Intraparenchymal injection of BDNF into the medial nucleus tractus solitarius (mNTS) | Suppression of food intake and body weight | ||
Intraparenchymal delivery of BDNF into the mNTS after ANA-12 (specific TrkB receptor antagonist) preadministration | Inhibition of the intake-suppressive effect of BDNF | ||
ICV (4th ventricle/hindbrain) leptin injection | Increase in the BDNF protein content within the DVC tissue | ||
Sprague-Dawley rats | BDNF injection into the PVH | Decrease in feeding and body weight; increase in energy expenditure; UCP1 expression increase in BAT | [41] Wang, C. et al., 2007 |
Animal Model | Intervention/Stimuli | Effects | Reference |
---|---|---|---|
Bdnf-e1−/− mice | Selective disruption of Bdnf expression from promoter 1 | Severe obesity, deficits of BAT-mediated thermogenesis, impairment of body temperature response to cold, down-expression of UCP1 and PCG1α in BAT | [47] You, H. et al., 2020 |
C57BL/KsJ-db/db mice (obese diabetic mice) | BDNF subcutaneous administration | Increase in body temperature and oxygen consumption | [16] Nakagawa, T. et al., 2000 |
C57BL/KsJ-db/db mice (obese diabetic mice) | BDNF central (ICV injection) and subcutaneous administration | Increase in UCP1 mRNA and protein in BAT, modulation of energy expenditure | [48] Tsuchida, A. et al., 2001 |
Diet-induced obese (DIO) C57BL/6 mice | Injection of a rAAV vector expressing the human BDNF gene in the hypothalamus | Reproduction of the effects induced by enriched environment: activation of the brown fat gene program (“browning’’ of WAT) and lean phenotype | [49] Cao, L. et al., 2011 |
Sprague–Dawley rats | BDNF injection into the VMH | Body weight reduction by decreasing food intake and increasing energy expenditure | [50] Wang, C. et al., 2010 |
Wistar rats | One week of forced moderate exercise | Improvement in spatial memory, increase in BDNF mRNA expression in the dentate gyrus | [53] Bechara, R.G. et al., 2014 |
C57BL/6 mice | Long-term physical exercise (4 weeks of treadmill and running wheel exercise) | Hippocampal increase in: (i) BDNF mRNA and protein (ii) synaptic load (iii) TrkB receptor levels in astrocytes | [58] Fahimi, A. et al., 2017 |
Sprague-Dawley rats | Short exercise period (voluntary exercise paradigm) | Enhancement in spatial learning and memory; increase in the mRNA levels of BDNF, TrkB receptor, synapsin I and CREB | [62] Vaynman, S. et al., 2004 |
Injection of a BDNF blocker into the hippocampus before the start of wheel running | Block of exercise benefits (reduction in: mRNA levels of BDNF, TrkB receptor, synapsin I and CREB) | ||
Muscle-specific BDNF Knockout Mice (BDNFMKO) | Muscle injury | Abnormal myogenic differentiation and regeneration | [70] Clow, C.; Jasmin, B.J., 2010 |
C57BL/KsJ-db/db mice (obese diabetic mice) | Chronic subcutaneous administration of BDNF | Improvement of glucose metabolism: enhancement of glucose utilization in peripheral tissues (skeletal muscle, heart, BAT and liver) | [75] Yamanaka, M. et al., 2007 |
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Di Rosa, M.C.; Zimbone, S.; Saab, M.W.; Tomasello, M.F. The Pleiotropic Potential of BDNF beyond Neurons: Implication for a Healthy Mind in a Healthy Body. Life 2021, 11, 1256. https://doi.org/10.3390/life11111256
Di Rosa MC, Zimbone S, Saab MW, Tomasello MF. The Pleiotropic Potential of BDNF beyond Neurons: Implication for a Healthy Mind in a Healthy Body. Life. 2021; 11(11):1256. https://doi.org/10.3390/life11111256
Chicago/Turabian StyleDi Rosa, Maria Carmela, Stefania Zimbone, Miriam Wissam Saab, and Marianna Flora Tomasello. 2021. "The Pleiotropic Potential of BDNF beyond Neurons: Implication for a Healthy Mind in a Healthy Body" Life 11, no. 11: 1256. https://doi.org/10.3390/life11111256