Time-dependent changes in rat brain cholinergic receptor expression after experimental brain injury.
Alterations in neurotransmitter receptor expression in the central nervous system may contribute to physiological and behavioral deficits that follow traumatic brain injury (TBI). Previous studies from our laboratory have demonstrated significant and widespread deficits in alpha7* nicotinic cholinergic receptor (alpha7* nAChr) expression 2 days following cortical contusion brain injury. The purpose of this study was to evaluate changes in alpha7* nAChr expression over a wider range of post-TBI recovery intervals. Animals were anesthetized and subjected to a moderate cortical contusion brain injury (2 mm cortical compression). Animals were euthanatized at various post-TBI time intervals, ranging from 1 h to 21 days, and quantitative autoradiography was used to evaluate cholinergic receptor subtype expression in the cerebral cortex and hippocampus. As previously reported, the alpha7* nAChr was the most sensitive target of TBI-induced plasticity. Significant decreases in alpha-[(125)I]-bungarotoxin (BTX) binding occurred as early as 1 h post-TBI, and persisted in some brain regions for up to 21 days. A kinetic analysis of changes in BTX binding, performed 2 days following brain injury, indicated that the binding deficits are not due to significant changes in receptor affinity. TBI-induced changes in alpha3*/alpha4* nACh receptors, muscarinic cholinergic receptors, and NMDA-type glutamate receptor expression were lower in magnitude, restricted to fewer brain regions and more transient in nature. Persistent deficits in alpha7* nAChr expression following TBI may contribute to impaired functional outcome following brain injury.
Verbois
S Leigh
SL
Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536-0082, USA.
Scheff
Stephen W
SW
Pauly
James R
JR
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000166:cytology / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism / Q000494:pharmacology; D002038:Bungarotoxins / Q000378:metabolism / Q000494:pharmacology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000378:metabolism / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism / Q000494:pharmacology; D007091:Image Processing, Computer-Assisted; D007700:Kinetics; D008297:Male; D018727:Muscarinic Antagonists / Q000378:metabolism / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D011725:Pyridines / Q000378:metabolism / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D011950:Receptors, Cholinergic / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic / Q000145:classification / Q000378:metabolism*; D013995:Time
D019086:Bridged Bicyclo Compounds, Heterocyclic; D002038:Bungarotoxins; D018691:Excitatory Amino Acid Antagonists; D018727:Muscarinic Antagonists; D018722:Nicotinic Agonists; D011725:Pyridines; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic; D011813:Quinuclidinyl Benzilate; D016291:Dizocilpine Maleate; C082748:epibatidine