PMID- 28258626
OWN - NLM
STAT- MEDLINE
DCOM- 20180226
LR  - 20181128
IS  - 1365-2826 (Electronic)
IS  - 0953-8194 (Linking)
VI  - 29
IP  - 4
DP  - 2017 Apr
TI  - Glucose concentrations modulate brain-derived neurotrophic factor responsiveness 
      of neurones in the paraventricular nucleus of the hypothalamus.
LID - 10.1111/jne.12464 [doi]
AB  - The hypothalamic paraventricular nucleus (PVN) is critical for normal energy 
      balance and has been shown to contain high levels of both brain-derived 
      neurotrophic factor (BDNF) and tropomyosin-receptor kinase B mRNA. 
      Microinjections of BDNF into the PVN increase energy expenditure, suggesting that 
      BDNF plays an important role in energy homeostasis through direct actions in this 
      nucleus. The present study aimed to examine the postsynaptic effects of BDNF on 
      the membrane potential of PVN neurones, and also to determine whether 
      extracellular glucose concentrations modulated these effects. We used 
      hypothalamic PVN slices from male Sprague-Dawley rats to perform whole cell 
      current-clamp recordings from PVN neurones. BDNF was bath applied at a 
      concentration of 2 nmol L(-1) and the effects on membrane potential determined. 
      BDNF caused depolarisations in 54% of neurones (n=25; mean+/-SEM, 8.9+/-1.2 mV) and 
      hyperpolarisations in 23% (n=11; -6.7+/-1.4 mV), whereas the remaining cells were 
      unaffected. These effects were maintained in the presence of tetrodotoxin (n=9; 
      56% depolarised, 22% hyperpolarised, 22% nonresponders), or the GABA(a) 
      antagonist bicuculline (n=12; 42% depolarised, 17% hyperpolarised, 41% 
      nonresponders), supporting the conclusion that these effects on membrane 
      potential were postsynaptic. Current-clamp recordings from PVN neurones next 
      examined the effects of BDNF on these neurones at varying extracellular glucose 
      concentrations. Larger proportions of PVN neurones hyperpolarised in response to 
      BDNF as the glucose concentrations decreased [10 mmol L(-1) glucose 23% (n=11) of 
      neurones hyperpolarised, whereas, at 0.2 mmol L(-1) glucose, 71% showed 
      hyperpolarising effects (n=12)]. Our findings reveal that BDNF has direct GABA(A) 
      independent effects on PVN neurones, which are modulated by local glucose 
      concentrations. The latter observation further emphasises the critical importance 
      of using physiologically relevant conditions in an investigation of the central 
      pathways involved in the regulation of energy homeostasis.
CI  - (c) 2017 British Society for Neuroendocrinology.
FAU - McIsaac, W
AU  - McIsaac W
AD  - Centre for Neuroscience, Queens University, Kingston, ON, Canada.
FAU - Ferguson, A V
AU  - Ferguson AV
AUID- ORCID: 0000-0003-1261-0036
AD  - Centre for Neuroscience, Queens University, Kingston, ON, Canada.
LA  - eng
GR  - MOP-12192/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neuroendocrinol
JT  - Journal of neuroendocrinology
JID - 8913461
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/administration & dosage/*physiology
MH  - Glucose/administration & dosage/*physiology
MH  - Male
MH  - Membrane Potentials
MH  - Neurons/*physiology
MH  - Paraventricular Hypothalamic Nucleus/*physiology
MH  - Rats, Sprague-Dawley
OTO - NOTNLM
OT  - electrophysiology
OT  - energy balance
OT  - glucose
EDAT- 2017/03/05 06:00
MHDA- 2018/02/27 06:00
CRDT- 2017/03/05 06:00
PHST- 2016/12/09 00:00 [received]
PHST- 2017/02/07 00:00 [revised]
PHST- 2017/02/20 00:00 [accepted]
PHST- 2017/03/05 06:00 [pubmed]
PHST- 2018/02/27 06:00 [medline]
PHST- 2017/03/05 06:00 [entrez]
AID - 10.1111/jne.12464 [doi]
PST - ppublish
SO  - J Neuroendocrinol. 2017 Apr;29(4). doi: 10.1111/jne.12464.