Serotonin regulates synaptic connections in the dentate molecular layer of adult rats via 5-HT1a receptors: evidence for a glial mechanism.
The present study sought to verify effects of 5-HT on synaptic density at the ultrastructural level, to determine whether the 5-HT1a receptor is important for the maintenance of synaptic connections and to obtain evidence implicating S100 beta in the apparent neurotrophic actions of 5-HT. Reduction of hippocampal 5-HT with para-chloroamphetamine (PCA) resulted in a significant decline in the synaptic density of the dentate molecular layer. Reduction of norepinephrine with DSP-4 produced a slight decrease in the number of molecular layer synapses, but this difference was not statistically different from control values. 5-HT1a antagonist treatment resulted in a decline in synaptic density comparable to that observed following PCA treatment. These observations suggest that 5-HT functions to maintain synaptic connections in the dentate molecular layer via a 5-HT1a mechanism. To determine whether the change in synaptic density was due to the action of 5-HT on neuronal receptors or astrocytic receptors, a monoclonal antibody against S100 beta was infused into the lateral ventricle for seven days. Controls received infusions of normal goat serum. Half of the rats from the anti-S100 beta and control groups also received daily injections of NAN-190. Anti-S100 beta infusion resulted in a significant (p < 0.01) decrease in synapses compared to serum controls. Concomitant NAN-190 administration did not enhance synapse loss in the anti-S100 beta group. The results of this study suggest that the maintenance of synaptic connections in the dentate molecular layer is influenced by S100 beta levels that are controlled by 5-HT stimulation of astrocytic 5-HT1a receptors.
Wilson
C C
CC
Department of Anatomy and Neurobiology, Saint Louis University Health Sciences Center, MO 63104, USA.
Faber
K M
KM
Haring
J H
JH
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D008854:Microscopy, Electron; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009457:Neuroglia / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology*; D009418:S100 Proteins / Q000276:immunology; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D000906:Antibodies; D010879:Piperazines; D011985:Receptors, Serotonin; D009418:S100 Proteins; D012702:Serotonin Antagonists; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; D012701:Serotonin