PMID- 15006692
OWN - NLM
STAT- MEDLINE
DCOM- 20040601
LR  - 20181130
IS  - 0969-9961 (Print)
IS  - 0969-9961 (Linking)
VI  - 15
IP  - 2
DP  - 2004 Mar
TI  - Apoptosis of vasopressinergic hypothalamic neurons in chronic diabetes mellitus.
PG  - 221-8
AB  - The hyperosmolality associated with diabetes mellitus triggers an increase in 
      neuronal activity and vasopressin production within magnocellular neurosecretory 
      cells (MNCs) of the hypothalamic supraoptic nucleus (SON). In this study, we 
      examined the effect of chronic diabetes on the function and survival of these 
      neurons. After 6 months, but not 6 weeks, of streptozotocin (STZ)-induced 
      diabetes, we observed an increase in the appearance of small hyperchromatic 
      neurons and a decrease in SON neuronal density. A subpopulation of neurons within 
      the SON at this time point demonstrated positive staining for cleaved caspase-3 
      and TUNEL, two markers of apoptosis. In addition, the number of 
      vasopressin-positive neurons was decreased. Markers for apoptosis did not 
      colocalize with vasopressin immunopositivity; this was probably due to a 
      diabetes-induced degenerative process causing downregulation of vasopressin 
      expression or depletion of neuropeptide. Although the phenotypes of the apoptotic 
      neurons were not identified, other SON neurons including oxytocin-producing 
      neurons are unlikely to be affected by chronic hyperglycemia. Microglial 
      hypertrophy and condensation were also observed in the 6-month diabetic SON. 
      Although upregulation of vasopressin production in response to acute 
      hyperosmolality is adaptive, prolonged overstimulation of vasopressin-producing 
      neurons in chronic diabetes results in neurodegeneration and apoptosis.
FAU - Klein, Joshua P
AU  - Klein JP
AD  - Department of Neurology and PVA/EPVA Center for Neuroscience and Regeneration 
      Research, Yale University School of Medicine, New Haven, CT 06510, USA.
FAU - Hains, Bryan C
AU  - Hains BC
FAU - Craner, Matthew J
AU  - Craner MJ
FAU - Black, Joel A
AU  - Black JA
FAU - Waxman, Stephen G
AU  - Waxman SG
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Antigens, Surface)
RN  - 0 (Avian Proteins)
RN  - 0 (Blood Proteins)
RN  - 0 (Bsg protein, Gallus gallus)
RN  - 0 (Bsg protein, rat)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Membrane Glycoproteins)
RN  - 11000-17-2 (Vasopressins)
RN  - 136894-56-9 (Basigin)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - *Antigens, CD
MH  - *Antigens, Neoplasm
MH  - *Antigens, Surface
MH  - Apoptosis/*physiology
MH  - *Avian Proteins
MH  - Basigin
MH  - *Blood Proteins
MH  - Caspase 3
MH  - Caspases/metabolism
MH  - Chronic Disease
MH  - Diabetes Mellitus, Experimental/metabolism/*pathology
MH  - Disease Models, Animal
MH  - Down-Regulation/physiology
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Gliosis/pathology/physiopathology
MH  - In Situ Nick-End Labeling
MH  - Male
MH  - Membrane Glycoproteins/metabolism
MH  - Microglia/pathology
MH  - Nerve Degeneration/*pathology
MH  - Neurons/metabolism/*pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Supraoptic Nucleus/metabolism/*pathology
MH  - Vasopressins/*metabolism
MH  - Water-Electrolyte Balance/physiology
EDAT- 2004/03/10 05:00
MHDA- 2004/06/02 05:00
CRDT- 2004/03/10 05:00
PHST- 2003/06/18 00:00 [received]
PHST- 2003/10/07 00:00 [revised]
PHST- 2003/10/23 00:00 [accepted]
PHST- 2004/03/10 05:00 [pubmed]
PHST- 2004/06/02 05:00 [medline]
PHST- 2004/03/10 05:00 [entrez]
AID - S0969996103002146 [pii]
AID - 10.1016/j.nbd.2003.10.009 [doi]
PST - ppublish
SO  - Neurobiol Dis. 2004 Mar;15(2):221-8. doi: 10.1016/j.nbd.2003.10.009.