Impairment of rat thymocyte differentiation and functions by neonatal capsaicin treatment is associated with induction of apoptosis.
The direct and indirect interaction between the nervous system and its transmitters with the immune system was evaluated in the rat by using the neurotoxin capsaicin (Caps). In the present study we investigated the effect of Caps administration to neonatal rats on thymocyte subpopulation distribution and functions at different times after treatment. Caps treatment results in a marked reduction of thymus weight and cellularity. As shown by immunofluorescence and FACS analysis, profound depletion of double negative (DN), double positive (DP), and single positive (SP) CD4(+) cells was already evident at day 7 after treatment and persisted until day 28. Reduced numbers of SP CD8(+) cells were observed only at later time points. Analysis of TCR phenotype indicates that CD5(+) TCR gamma/delta(+) are particularly sensitive to neonatal Caps treatment. Caps-induced thymocyte depletion was associated with reduced proliferation in response to T cell mitogens. Moreover, in situ TUNEL reaction and agarose gel electrophoresis indicate that neonatal Caps treatment induces apoptosis of thymus cells. Morphological analysis reveals the presence of apoptotic cells in the subcapsular thymus cortical region. Overall our results suggest that Caps when administered at birth, profoundly affects T cell differentiation, likely through its ability to activate apoptotic cell death program.
Santoni
G
G
Department of Pharmacological Sciences and Experimental Medicine, University of Camerino, Camerino, Italy. santoni@cambio.unicam.it
Perfumi
M C
MC
Pompei
P
P
Spreghini
E
E
Lucciarini
R
R
Martarelli
D
D
Staffolani
M
M
Piccoli
M
M
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D017209:Apoptosis; D015704:CD4 Antigens / Q000032:analysis; D018956:CD5 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002211:Capsaicin / Q000494:pharmacology; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D005260:Female; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000502:physiology
D015704:CD4 Antigens; D018956:CD5 Antigens; D016827:CD8 Antigens; D008934:Mitogens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D002211:Capsaicin