PMID- 25693197 OWN - NLM STAT- MEDLINE DCOM- 20151116 LR - 20220316 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 10 IP - 2 DP - 2015 TI - The transfection of BDNF to dopamine neurons potentiates the effect of dopamine D3 receptor agonist recovering the striatal innervation, dendritic spines and motor behavior in an aged rat model of Parkinson's disease. PG - e0117391 LID - 10.1371/journal.pone.0117391 [doi] LID - e0117391 AB - The progressive degeneration of the dopamine neurons of the pars compacta of substantia nigra and the consequent loss of the dopamine innervation of the striatum leads to the impairment of motor behavior in Parkinson's disease. Accordingly, an efficient therapy of the disease should protect and regenerate the dopamine neurons of the substantia nigra and the dopamine innervation of the striatum. Nigral neurons express Brain Derived Neurotropic Factor (BDNF) and dopamine D3 receptors, both of which protect the dopamine neurons. The chronic activation of dopamine D3 receptors by their agonists, in addition, restores, in part, the dopamine innervation of the striatum. Here we explored whether the over-expression of BDNF by dopamine neurons potentiates the effect of the activation of D3 receptors restoring nigrostriatal innervation. Twelve-month old Wistar rats were unilaterally injected with 6-hydroxydopamine into the striatum. Five months later, rats were treated with the D3 agonist 7-hydroxy-N,N-di-n-propy1-2-aminotetralin (7-OH-DPAT) administered i.p. during 4(1/2) months via osmotic pumps and the BDNF gene transfection into nigral cells using the neurotensin-polyplex nanovector (a non-viral transfection) that selectively transfect the dopamine neurons via the high-affinity neurotensin receptor expressed by these neurons. Two months after the withdrawal of 7-OH-DPAT when rats were aged (24 months old), immunohistochemistry assays were made. The over-expression of BDNF in rats receiving the D3 agonist normalized gait and motor coordination; in addition, it eliminated the muscle rigidity produced by the loss of dopamine. The recovery of motor behavior was associated with the recovery of the nigral neurons, the dopamine innervation of the striatum and of the number of dendritic spines of the striatal neurons. Thus, the over-expression of BDNF in dopamine neurons associated with the chronic activation of the D3 receptors appears to be a promising strategy for restoring dopamine neurons in Parkinson's disease. FAU - Razgado-Hernandez, Luis F AU - Razgado-Hernandez LF AD - Departamento de Fisiologia, Biofisica y Neurociencias, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional (CINVESTAV), Mexico D.F., Mexico. FAU - Espadas-Alvarez, Armando J AU - Espadas-Alvarez AJ AD - Departamento de Fisiologia, Biofisica y Neurociencias, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional (CINVESTAV), Mexico D.F., Mexico. FAU - Reyna-Velazquez, Patricia AU - Reyna-Velazquez P AD - Departamento de Fisiologia, Biofisica y Neurociencias, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional (CINVESTAV), Mexico D.F., Mexico. FAU - Sierra-Sanchez, Arturo AU - Sierra-Sanchez A AD - Departamento de Fisiologia, Biofisica y Neurociencias, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional (CINVESTAV), Mexico D.F., Mexico. FAU - Anaya-Martinez, Veronica AU - Anaya-Martinez V AD - Neuromorphology Lab, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autonoma de Mexico (UNAM), Tlalnepantla, Estado de Mexico, Mexico. FAU - Jimenez-Estrada, Ismael AU - Jimenez-Estrada I AD - Departamento de Fisiologia, Biofisica y Neurociencias, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional (CINVESTAV), Mexico D.F., Mexico. FAU - Bannon, Michael J AU - Bannon MJ AD - Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan, United States of America. FAU - Martinez-Fong, Daniel AU - Martinez-Fong D AD - Departamento de Fisiologia, Biofisica y Neurociencias, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional (CINVESTAV), Mexico D.F., Mexico; Programa de Nanociencias y Nanotecnologia, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional (CINVESTAV), Mexico D.F., Mexico. FAU - Aceves-Ruiz, Jorge AU - Aceves-Ruiz J AD - Departamento de Fisiologia, Biofisica y Neurociencias, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional (CINVESTAV), Mexico D.F., Mexico. LA - eng GR - R01 DA006470/DA/NIDA NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150218 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Dopamine Agonists) RN - 0 (Receptors, Dopamine D3) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) SB - IM MH - Animals MH - Biomechanical Phenomena/drug effects/genetics MH - Brain-Derived Neurotrophic Factor/*genetics MH - Dendritic Spines/drug effects/*physiology MH - Disease Models, Animal MH - Dopamine Agonists/*pharmacology MH - Dopaminergic Neurons/drug effects/*pathology MH - Gait/drug effects/genetics MH - Male MH - Motor Activity/drug effects/genetics MH - Muscles/drug effects/physiopathology MH - Neostriatum/drug effects/*physiopathology MH - Parkinson Disease/genetics/pathology/*physiopathology MH - Psychomotor Performance/drug effects MH - Rats MH - Rats, Wistar MH - Receptors, Dopamine D3/*metabolism MH - Recovery of Function/drug effects/genetics MH - Regeneration/drug effects/genetics MH - Transfection MH - Tyrosine 3-Monooxygenase/metabolism PMC - PMC4332861 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2015/02/19 06:00 MHDA- 2015/11/17 06:00 PMCR- 2015/02/18 CRDT- 2015/02/19 06:00 PHST- 2014/09/26 00:00 [received] PHST- 2014/12/21 00:00 [accepted] PHST- 2015/02/19 06:00 [entrez] PHST- 2015/02/19 06:00 [pubmed] PHST- 2015/11/17 06:00 [medline] PHST- 2015/02/18 00:00 [pmc-release] AID - PONE-D-14-43329 [pii] AID - 10.1371/journal.pone.0117391 [doi] PST - epublish SO - PLoS One. 2015 Feb 18;10(2):e0117391. doi: 10.1371/journal.pone.0117391. eCollection 2015.