Neurotrophic factor mRNA expression in dentate gyrus is increased following angular bundle transection

Area of Science:

• Neuroscience
• Molecular Biology
• Neuroanatomy

Background:

• Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) mRNA are highly expressed in the hippocampal formation.
• The angular bundle relays cortical information to the hippocampal formation via the entorhinal cortex.

Purpose of the Study:

• To investigate the effect of transecting the angular bundle on NGF and BDNF mRNA levels in the hippocampal formation.
• To determine the time course and specificity of the neurotrophin mRNA response to cortical input disruption.

Main Methods:

• Unilateral transection of the angular bundle in the central nervous system.
• Quantitative analysis of NGF and BDNF mRNA expression using hybridization.
• Assessment of c-fos mRNA induction and the effect of pharmacological and surgical interventions (AP-5, CNQX, cholinergic denervation).

Main Results:

• Transection of the angular bundle significantly increased NGF and BDNF mRNA in the ipsilateral dentate gyrus stratum granulosum within 4 hours.
• The elevated mRNA levels returned to baseline within 24 hours and persisted for at least 5 days.
• Increased c-fos mRNA expression preceded the neurotrophin mRNA induction, which was unaffected by AP-5, CNQX, or cholinergic denervation.

Conclusions:

• Disruption of cortical input to the hippocampal formation selectively upregulates NGF and BDNF mRNA in the dentate gyrus.
• This upregulation may represent an early molecular event in synaptic reorganization following entorhinal cortex damage.
• The findings highlight the dynamic regulation of neurotrophin expression in response to injury in the central nervous system.