Effects of neurotrophins on synaptic protein expression in the visual cortex of dark-reared rats.
Total lack of visual experience [dark rearing (DR)] is known to prolong the critical period and delay development of sensory functions in mammalian visual cortex. Recent results show that neurotrophins (NTs) counteract the effects of DR on functional properties of visual cortical cells and exert a strong control on critical period duration. NTs are known to modulate the development and synaptic efficacy of neurotransmitter systems that are affected by DR. However, it is still unknown whether the actions of NTs in dark-reared animals involve interaction with neurotransmitter systems. We have studied the effects of DR on the expression of key molecules in the glutamatergic and GABAergic systems in control and NT-treated animals. We have found that DR reduced the expression of the NMDA receptor 2A subunit and its associated protein PSD-95 (postsynaptic density-95), of GRIP (AMPA glutamate receptor interacting protein), and of the biosynthetic enzyme GAD (glutamic acid decarboxylase). Returning dark-reared animals to light for 2 hr restored normal expression of the above-mentioned proteins almost completely. NT treatment specifically counteracts DR effects; NGF acts primarily on the NMDA system, whereas BDNF acts primarily on the GABAergic system. Finally, the action of NT4 seems to involve both excitatory and inhibitory systems. These data demonstrate that different NTs counteract DR effects by modulating the expression of key molecules of the excitatory and inhibitory neurotransmitter systems.
Cotrufo
Tiziana
T
Scuola Normale Superiore, 56126 Pisa, Italy.
Viegi
Alessandro
A
Berardi
Nicoletta
N
Bozzi
Yuri
Y
Mascia
Laura
L
Maffei
Lamberto
L
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D003624:Darkness; D003720:Densitometry; D000076122:Disks Large Homolog 4 Protein; D005968:Glutamate Decarboxylase / Q000378:metabolism; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000378:metabolism; D008027:Light; D008565:Membrane Proteins; D020932:Nerve Growth Factor / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D010775:Photic Stimulation; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D017470:Receptors, Glutamate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012683:Sensory Deprivation / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D014793:Visual Cortex / Q000187:drug effects / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D002352:Carrier Proteins; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; C491308:Grip1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; C120997:NR2A NMDA receptor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D011506:Proteins; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C033652:postsynaptic density proteins; D020932:Nerve Growth Factor; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2; C073922:neurotrophin 4