“Selective regional changes of pre-synaptic proteins in the developing brain after neonatal hypoxia”.

VALDEZ S R; PATTERSON, SEAN I.; SELTZER, ALICIA M

Pucón, Chile

Workshop; Neurotoxicity Meeting: mechanism for neurodegenerative disorders.; 2001

Sociedad de Farmacología Chilena, UN Chile.

Perinatal hypoxia is able to disturb the development of the CNS without causing gross anatomical changes. We believe the developing neurotransmitter system can be target for the insult at the level of nerve terminals. This disturbance may be exerted in such way that only slight changes occur at the molecular level but important to cause for example, the behavioral and cognitive alteration related to hypoxia. We studied whether regional or selective alteration in presynaptic proteins occur after submitting the animals to an episode of mild postnatal hypoxia at postnatal day 4 th (PND4). We measured the immunoreactivity (IR) by Western Blot (WB) of presynaptic proteins of the SNARE complex: synaptobrevin (VAMP), SNAP-25, syntaxin (SYN) and also GAP-43 involved in axonal growth and plasticity. Immunoblots of P2 fractions (membrane enriched preparation) were prepared from hippocampus, striatum and cerebral cortex at 7, 14, 21 and 36 days post-hypoxia (DPH). Results: Cerebral cortex: at 7 DPH the IR of all proteins studied were lower than controls and during the period of our analysis all of them showed a steady increase above control, with GAP-43 reaching the highest values (34% above controls). Hippocampus: IR of SNARE proteins and GAP-43 was similar to control except for VAMP, which presented values lower than control at 7 DPH. Striatum: IR to both SNARE and GAP-43 proteins increased during development. VAMP showed the highest values of IR at 21 DPH (46% above control). Light microscopy immunohistochemistry showed the characteristic pattern of VAMP staining but not apparent changes in the IR distribution were revealed by this technique. Conclusions: VAMP located in hippocampus and striatum, is likely to be the most vulnerable protein to hypoxia while in the cerebral cortex was GAP-43. We demostrated that mild hipoxia during perinatal period could modify the pattern of neurotransmitter release by altering the behavior of proteins that participate in the synaptic cycle and establishment of axonal pathways.