PMID- 31626851
OWN - NLM
STAT- MEDLINE
DCOM- 20210429
LR  - 20210429
IS  - 1872-7549 (Electronic)
IS  - 0166-4328 (Linking)
VI  - 378
DP  - 2020 Jan 27
TI  - Dopamine D1 receptor agonism induces dynamin related protein-1 inhibition to 
      improve mitochondrial biogenesis and dopaminergic neurogenesis in rat model of 
      Parkinson's disease.
PG  - 112304
LID - S0166-4328(19)30978-7 [pii]
LID - 10.1016/j.bbr.2019.112304 [doi]
AB  - Dopamine (DA) neurotransmitter act on dopamine receptors (D1-D5) to regulate 
      motor functions, reward, addiction and cognitive behavior. The depletion of DA in 
      midbrain due to degeneration of nigral dopaminergic (DAergic) neurons leads to 
      Parkinson's disease (PD). DA agonist and levodopa (L-DOPA) are the only therapies 
      used for symptomatic relief in PD. However, the role of DA receptors in PD 
      pathogenesis and how they are associated with mitochondrial functions and DAergic 
      neurogenesis is still not known. Here, we investigated the mechanistic aspect of 
      DA D1 receptor mediated control of DAergic neurogenesis, motor behavior and 
      mitochondrial functions in rat PD model. The pharmacological activation of D1 
      receptors markedly improved motor deficits, mitochondrial biogenesis, ATP levels, 
      mitochondrial membrane potential and defended nigral DAergic neurons against 
      6-hydroxydopamine (6-OHDA) induced neurotoxicity in adult rats. However, the D1 
      agonist mediated effects were abolished following D1 receptor antagonist 
      treatment in 6-OHDA lesioned rats. Interestingly, pharmacological inhibition of 
      dynamin related protein-1 (Drp-1) by Mdivi-1 in D1 antagonist treated PD rats, 
      significantly restored behavioral deficits, mitochondrial functions, 
      mitochondrial biogenesis and increased the number of newborn DAergic neurons in 
      substantia nigra pars compacta (SNpc). Drp-1 inhibition mediated neuroprotective 
      effects in PD rats were associated with increased level of protein kinase-B/Akt 
      and extracellular-signal-regulated kinase (ERK). Taken together, our data 
      suggests that dopamine D1 receptor mediated reduction in mitochondrial fission 
      and enhanced DAergic neurogenesis may involve Drp-1 inhibition which led to 
      improved behavioral recovery in PD rats.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Mishra, Akanksha
AU  - Mishra A
AD  - Division of Neuroscience and Ageing biology, CSIR-Central Drug Research 
      Institute, Lucknow (U.P.), India; Academy of Scientific and Innovative Research, 
      New Delhi, India.
FAU - Singh, Sonu
AU  - Singh S
AD  - Division of Neuroscience and Ageing biology, CSIR-Central Drug Research 
      Institute, Lucknow (U.P.), India; L4078, Department of Neuroscience, School of 
      Medicine, University of Connecticut (Uconn) Health Center, 263 Farmington Avenue.
FAU - Tiwari, Virendra
AU  - Tiwari V
AD  - Division of Neuroscience and Ageing biology, CSIR-Central Drug Research 
      Institute, Lucknow (U.P.), India; Academy of Scientific and Innovative Research, 
      New Delhi, India.
FAU - Bano, Shameema
AU  - Bano S
AD  - Division of Neuroscience and Ageing biology, CSIR-Central Drug Research 
      Institute, Lucknow (U.P.), India.
FAU - Shukla, Shubha
AU  - Shukla S
AD  - Division of Neuroscience and Ageing biology, CSIR-Central Drug Research 
      Institute, Lucknow (U.P.), India; Academy of Scientific and Innovative Research, 
      New Delhi, India. Electronic address: shubha_shukla@cdri.res.in.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191015
PL  - Netherlands
TA  - Behav Brain Res
JT  - Behavioural brain research
JID - 8004872
RN  - 0 (Dopamine Agonists)
RN  - 0 (Dopamine Antagonists)
RN  - 0 (Receptors, Dopamine D1)
RN  - 8HW4YBZ748 (Oxidopamine)
RN  - EC 3.6.5.5 (Dnm1l protein, rat)
RN  - EC 3.6.5.5 (Dynamins)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/*drug effects
MH  - Disease Models, Animal
MH  - Dopamine Agonists/administration & dosage/*pharmacology
MH  - Dopamine Antagonists/pharmacology
MH  - Dopaminergic Neurons/*drug effects
MH  - Dynamins/antagonists & inhibitors/*drug effects
MH  - Locomotion/*drug effects
MH  - Male
MH  - Mitochondria/*drug effects
MH  - Neurogenesis/*drug effects
MH  - *Organelle Biogenesis
MH  - Oxidopamine/toxicity
MH  - Parkinson Disease/*drug therapy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Dopamine D1/*agonists/antagonists & inhibitors
OTO - NOTNLM
OT  - Dopamine receptor
OT  - Dynamin related protein-1 (Drp-1)
OT  - Mitochondrial biogenesis
OT  - Neurogenesis
OT  - Parkinson's disease
EDAT- 2019/10/19 06:00
MHDA- 2021/04/30 06:00
CRDT- 2019/10/19 06:00
PHST- 2019/06/24 00:00 [received]
PHST- 2019/09/26 00:00 [revised]
PHST- 2019/10/14 00:00 [accepted]
PHST- 2019/10/19 06:00 [pubmed]
PHST- 2021/04/30 06:00 [medline]
PHST- 2019/10/19 06:00 [entrez]
AID - S0166-4328(19)30978-7 [pii]
AID - 10.1016/j.bbr.2019.112304 [doi]
PST - ppublish
SO  - Behav Brain Res. 2020 Jan 27;378:112304. doi: 10.1016/j.bbr.2019.112304. Epub 
      2019 Oct 15.