Thyroid hormone regulates neurotransmitter release in neonatal rat hippocampus.
Thyroid hormone is essential for the normal maturation and function of the mammalian CNS. Thyroid hormone deficiency during a critical period of development profoundly affects cognitive functions such as learning and memory. However, the possible electrophysiological alterations that could underlie these learning deficits in hypothyroid animals remain largely unexplored. In this work, we have studied the possible effect of thyroid hormone on short-term synaptic plasticity, which is hypothesized to be a neural substrate of short-term memory. We compared short-term modification of the excitatory postsynaptic potential in hippocampal slices between control and hypothyroid rats. Electrophysiological studies reveal that paired-pulse facilitation is strongly altered in the hypothyroid rats. In addition, hypothyroid rats exhibit an increase in the Ca(2+)-dependent neurotransmitter release. These alterations are basically reversible when thyroid hormone is administered. In order to examine the possible molecular mechanisms underlying these synaptic changes, we compared the expression of synapsin I, synaptotagmin I, syntaxin, and alpha-Ca(2+)/calmodulin kinase II between control and hypothyroid hippocampus. Our results show that the levels of synapsin I and synaptotagmin I are increased in the hypothyroid rats, which suggests that the genes encoding these proteins are implicated in the action of thyroid hormone on neurotransmitter release. Taken together, the results from this study suggest that thyroid hormone may modulate the probability of neurotransmitter release.
Vara
H
H
Departamento de Fisiología, Facultad de Medicina, Universidad Complutense, Ciudad Universitaria, 28040 Madrid, Spain.
Martínez
B
B
Santos
A
A
Colino
A
A
D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000172:deficiency; D002135:Calcium-Binding Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005333:Fetus; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development* / Q000503:physiopathology; D007037:Hypothyroidism / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008562:Membrane Glycoproteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D016704:Synapsins / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D050863:Synaptotagmin I; D050857:Synaptotagmins; D014284:Triiodothyronine / Q000172:deficiency* / Q000494:pharmacology
D002135:Calcium-Binding Proteins; D018691:Excitatory Amino Acid Antagonists; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D016704:Synapsins; D050863:Synaptotagmin I; C494312:Syt1 protein, rat; D014284:Triiodothyronine; D050857:Synaptotagmins; D018698:Glutamic Acid; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000241:Adenosine; D002118:Calcium