PMID- 30370451
OWN - NLM
STAT- MEDLINE
DCOM- 20200622
LR  - 20200622
IS  - 1435-1463 (Electronic)
IS  - 0300-9564 (Linking)
VI  - 126
IP  - 2
DP  - 2019 Feb
TI  - Neurogenesis within the hippocampus after chronic methylphenidate exposure.
PG  - 201-209
LID - 10.1007/s00702-018-1949-2 [doi]
AB  - Methylphenidate is a psychostimulant used to treat attention deficit 
      hyperactivity disorder. Neurogenesis occurs throughout adulthood within the 
      dentate gyrus of the hippocampus and can be altered by psychoactive medications; 
      however, the impact of methylphenidate on neurogenesis is not fully understood. 
      We investigated the effects of chronic low (1 mg/kg) and high (10 mg/kg) 
      intraperitoneal doses of methylphenidate on neurogenesis in mouse hippocampus 
      following 28 days and 56 days of treatment. Interestingly, methylphenidate, at 
      both doses, increased neurogenesis. However, if methylphenidate treatment was not 
      continued, the newly generated cells did not survive after 28 days. If treatment 
      was continued, the newly generated neurons survived only in the mice receiving 
      low-dose methylphenidate. To investigate the mechanism for this effect, we 
      examined levels of proteins linked to cell proliferation in the hippocampus, 
      including brain-derived neurotrophic factor (BDNF), glial cell line-derived 
      neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF), 
      tropomyosin receptor kinase B (TrkB), and beta-catenin. BDNF or GDNF levels were 
      not significantly different between groups. However, hippocampal VEGF, TrkB, and 
      beta-catenin were significantly increased in mice receiving low-dose 
      methylphenidate for 28 days compared to controls. Interestingly, high-dose 
      methylphenidate significantly decreased beta-catenin after 28 days and decreased 
      VEGF, beta-catenin, and TrkB after 56 days compared to controls. Thus, low-dose 
      methylphenidate appears to increase cell proliferation and cell survival in the 
      hippocampus, and these effects may be mediated by increase in VEGF, TrkB, and 
      beta-catenin. While high dose methylphenidate may initially increase neuronal 
      proliferation, newly generated neurons are unable to survive long-term, possibly 
      due to decrease in VEGF, TrkB and beta-catenin.
FAU - Oakes, Hannah V
AU  - Oakes HV
AD  - Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East 
      Tennessee State University, Johnson City, TN, 37614, USA.
FAU - DeVee, Carley E
AU  - DeVee CE
AD  - Department of Pharmacy Practice, Presbyterian College School of Pharmacy, 
      Clinton, SC, 29325, USA.
FAU - Farmer, Brandon
AU  - Farmer B
AD  - Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East 
      Tennessee State University, Johnson City, TN, 37614, USA.
FAU - Allen, Serena A
AU  - Allen SA
AD  - Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East 
      Tennessee State University, Johnson City, TN, 37614, USA.
FAU - Hall, Alexis N
AU  - Hall AN
AD  - Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East 
      Tennessee State University, Johnson City, TN, 37614, USA.
FAU - Ensley, Tucker
AU  - Ensley T
AD  - Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East 
      Tennessee State University, Johnson City, TN, 37614, USA.
FAU - Medlock, Kristen
AU  - Medlock K
AD  - Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East 
      Tennessee State University, Johnson City, TN, 37614, USA.
FAU - Hanley, Angela
AU  - Hanley A
AD  - Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East 
      Tennessee State University, Johnson City, TN, 37614, USA.
FAU - Pond, Brooks B
AU  - Pond BB
AUID- ORCID: 0000-0001-5209-334X
AD  - Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East 
      Tennessee State University, Johnson City, TN, 37614, USA. pond@etsu.edu.
LA  - eng
GR  - C06 RR030651/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20181028
PL  - Austria
TA  - J Neural Transm (Vienna)
JT  - Journal of neural transmission (Vienna, Austria : 1996)
JID - 9702341
RN  - 0 (Bdnf protein, mouse)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (CTNNB1 protein, mouse)
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Gdnf protein, mouse)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (beta Catenin)
RN  - 0 (vascular endothelial growth factor A, mouse)
RN  - 207ZZ9QZ49 (Methylphenidate)
RN  - EC 2.7.10.1 (Ntrk2 protein, mouse)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cell Proliferation/*drug effects
MH  - Cell Survival/*drug effects
MH  - Central Nervous System Stimulants/administration & dosage/*pharmacology
MH  - Glial Cell Line-Derived Neurotrophic Factor/metabolism
MH  - Hippocampus/*drug effects/*metabolism
MH  - Membrane Glycoproteins/*metabolism
MH  - Methylphenidate/administration & dosage/*pharmacology
MH  - Mice
MH  - Neurogenesis/*drug effects
MH  - Protein-Tyrosine Kinases/*metabolism
MH  - Vascular Endothelial Growth Factor A/*metabolism
MH  - beta Catenin/*metabolism
OTO - NOTNLM
OT  - Dentate gyrus
OT  - Hippocampus
OT  - Methylphenidate
OT  - Neurogenesis
EDAT- 2018/10/30 06:00
MHDA- 2020/06/23 06:00
CRDT- 2018/10/30 06:00
PHST- 2018/08/29 00:00 [received]
PHST- 2018/10/23 00:00 [accepted]
PHST- 2018/10/30 06:00 [pubmed]
PHST- 2020/06/23 06:00 [medline]
PHST- 2018/10/30 06:00 [entrez]
AID - 10.1007/s00702-018-1949-2 [pii]
AID - 10.1007/s00702-018-1949-2 [doi]
PST - ppublish
SO  - J Neural Transm (Vienna). 2019 Feb;126(2):201-209. doi: 
      10.1007/s00702-018-1949-2. Epub 2018 Oct 28.